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  • 151.
    Ekblom, Kim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Marklund, Stefan L
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Jansson, Jan-Håkan
    Osterman, Pia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Weinehall, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Response to letter regarding article "Plasma bilirubin and UGT1A1*28 are not protective factors against first-time myocardial infarction in a prospective nested case-referent setting"2011Ingår i: Circulation: Cardiovascular Genetics, ISSN 1942-325X, E-ISSN 1942-3268, Vol. 4, nr 1, s. e2-Artikel i tidskrift (Refereegranskat)
  • 152.
    Ekblom, Kim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Marklund, Stefan L
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Johansson, Lars
    Osterman, Pia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Weinehall, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wiklund, Per-Gunnar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Bilirubin and UGT1A1*28 are not associated with lower risk for ischemic stroke in a prospective nested case-referent setting.2010Ingår i: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 30, nr 6, s. 590-596Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Bilirubin, an antioxidant, has been associated with reduced cardiovascular disease risk. A major cause of elevated plasma bilirubin is the common UGT1A1*28 promoter polymorphism in the gene of the bilirubin-conjugating enzyme UDP-glucuronosyltransferase 1A1, which reduces transcription by 70%. Earlier studies reporting a protective effect of bilirubin on stroke have not included analysis of UGT1A1*28. The purpose of this study is to investigate if bilirubin and UGT1A1*28 are protective against ischemic stroke in a prospective case-referent setting. Methods: Cases with first-ever ischemic stroke (n = 231; median lag time 4.9 years) and 462 matched referents from the Northern Sweden Health and Disease Study Cohort were included. Plasma bilirubin was measured and UGT1A1*28 was analyzed by fragment analysis. Results: Plasma bilirubin was lower in cases than in referents, but the difference reached significance only for women. The UGT1A1*28 polymorphism (allele frequency 30%) showed a strong gene-dose relationship with bilirubin levels both among cases and referents, but was not associated with risk for stroke. Among multiple other variables analyzed, the strongest correlation with bilirubin was found for plasma iron. Conclusions: There was no evidence for a protective effect of the UGT1A1*28 polymorphism against stroke and consequently neither for bilirubin. The findings suggest that other factors influencing the risk for stroke might also affect bilirubin levels.

  • 153.
    Ekblom, Kim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Marklund, Stefan L
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Johansson, Lars
    Medicinkliniken, Skellefteå lasarett.
    Osterman, Pia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Weinehall, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Wiklund, Per-Gunnar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Bilirubin and UGT1A1*28, are not associated with lower risk for ischemic stroke in a prospective nested case-referent settingArtikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Bilirubin, an antioxidant, has been associated with reduced cardiovascular disease risk. A major cause of elevated plasma bilirubin is the common UGT1A1*28 promoter polymorphism in the gene of the bilirubin-conjugating enzyme UDP-glucuronosyltransferase-1A1, which reduces transcription by 70%. Earlier studies reporting a protective effect of bilirubin on stroke, have not included analysis of UGT1A1*28. The purpose of this study is to investigate if bilirubin and UGT1A1*28 are protective against ischemic stroke in a prospective case-referent setting.

    Methods: Cases with first-ever ischemic stroke (n=231; median lag time 4.9 years), and 462 matched referents from the The Northern Sweden Health and Disease Study Cohort were included. Plasma bilirubin was measured and UGT1A1*28 was analyzed by fragment analysis.

    Results: Plasma bilirubin was lower in cases than in referents, but the difference reached significance only for women. The UGT1A1*28 polymorphism (allele frequency 30%), showed a strong gene-dose relationship with bilirubin levels both among cases and referents, but was not associated with risk for stroke. Among multiple other variables analysed the strongest correlation with bilirubin was found for plasma iron.

    Conclusions: There was no evidence for a protective effect of the UGT1A1*28 polymorphism against stroke and consequently neither for bilirubin. The findings suggest that other factors influencing the risk for stroke also might affect bilirubin levels.

  • 154.
    Ekblom, Kim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Marklund, Stefan L.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Weinehall, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Iron Biomarkers in Plasma, HFE Genotypes, and the Risk for Colorectal Cancer in a Prospective Setting2012Ingår i: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 55, nr 3, s. 337-344Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: High iron levels can increase the formation of noxious oxygen radicals, which are thought to promote carcinogenesis. OBJECTIVE: The aim of this prospective study was to determine whether iron biomarkers and HFE genotypes, which influence iron regulation, constitute risk factors for colorectal cancer. DESIGN: This is a prospective nested case-referent study. SETTINGS: The study was performed within the population-based Northern Sweden Health and Disease Study. PATIENTS: The study included 226 cases of colorectal cancer and 437 matched referents. MAIN OUTCOME MEASURES: Conditional regression analysis was performed. Adjustments for smoking, smoking and BMI, and HFE C282Y and H63D were performed. RESULTS: The highest quintile of total iron-binding capacity showed significantly higher risk for colorectal cancer, unadjusted OR 2.35 (95% CI 1.38-4.02). When stratified by sex, the findings were only present in women (OR 3.34 (95% CI 1.59-7.02)). Ferritin was associated with reduced risk throughout quintiles 2 to 5 both in univariate and multivariate models. LIMITATIONS: Colorectal cancer may influence iron markers because of occult bleeding. Homozygotes for HFE C282Y were too few to make conclusions for this group. The relatively short follow-up time might be insufficient to detect risk of iron biomarkers. CONCLUSIONS: High iron levels do not increase the risk of colorectal cancer. HFE genotypes influencing iron uptake had no effect on colorectal cancer risk.

  • 155.
    Eklöf, Vincy
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    The reduced folate carrier (RFC1) 80G>A and folate hydrolase 1 (FOLH1) 1561C>T polymorphisms and the risk of colorectal cancer: a nested case-referent study2008Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 68, nr 5, s. 393-401Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. Polymorphisms in genes involved in folate uptake and metabolism may affect folate status and, thereby, the risk of cancer. In this nested case‐referent study, we related two such polymorphisms, reduced folate carrier (RFC1) 80G>A and folate hydrolase 1 (FOLH1) 1561C>T, to the risk of colorectal cancer, taking into account pre‐diagnostic plasma folate and total homocysteine concentrations and the MTHFR 677C>T polymorphism, which were analysed in a previous study.

    Material and methods. Subjects were 220 cases and 414 matched referents from the population‐based Northern Sweden Health and Disease Study.

    Results. The RFC1 80A‐allele was associated with reduced plasma folate and elevated plasma total homocysteine concentrations, but the result was statistically significant only for folate. In contrast, the FOLH1 1561T‐allele was associated with higher plasma folate and reduced plasma total homocysteine concentrations, and the result was statistically significant only for homocysteine. Neither polymorphism was related to the risk of colorectal cancer, either in univariate analysis or after adjusting for body mass index, current smoking, recreational and occupational physical activity and alcohol intake. Further adjustment for folate or homocysteine status or the MTHFR 677C>T polymorphism did not affect risk estimates. Subjects with the RFC1 80AA genotype in combination with low plasma folate concentrations or the MTHFR 677TT genotype had a reduced risk of colorectal cancer of borderline statistical significance.

    Conclusions. These findings suggest that although the RFC1 80G>A and FOLH1 1561C>T polymorphisms may influence folate status, they are not likely to have a major independent role in the development of colorectal cancer.

    Read More: http://informahealthcare.com/doi/abs/10.1080/00365510701805431

  • 156. Elena, J. W.
    et al.
    Steplowski, E.
    Yu, K.
    Hartge, P.
    Tobias, G. S.
    Brotzman, M. J.
    Chanock, S. J.
    Stolzenberg-Solomon, R. Z.
    Arslan, A. A.
    Bueno-De-Mesquita, H. B.
    Helzlsouer, K.
    Jacobs, E. J.
    Lacroix, A.
    Petersen, G.
    Zheng, W.
    Albanes, D.
    Allen, N. E.
    Amundadottir, L.
    Bao, Y.
    Boeing, H.
    Boutron-Ruault, M. -C
    Buring, J. E.
    Gaziano, J. M.
    Giovannucci, E. L.
    Duell, E. J.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Howard, B. V.
    Hunter, D. J.
    Hutchinson, A.
    Jacobs, K. B.
    Kooperberg, C.
    Kraft, P.
    Mendelsohn, J. B.
    Michaud, D. S.
    Palli, D.
    Phillips, L. S.
    Overvad, K.
    Patel, A. V.
    Sansbury, L.
    Shu, X. -O
    Simon, M. S.
    Slimani, N.
    Trichopoulos, D.
    Visvanathan, K.
    Virtamo, J.
    Wolpin, B. M.
    Zeleniuch-Jacquotte, A.
    Fuchs, C. S.
    Hoover, R. N.
    Gross, M.
    Diabetes and risk of pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium2013Ingår i: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 24, nr 1, s. 13-25Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Diabetes is a suspected risk factor for pancreatic cancer, but questions remain about whether it is a risk factor or a result of the disease. This study prospectively examined the association between diabetes and the risk of pancreatic adenocarcinoma in pooled data from the NCI pancreatic cancer cohort consortium (PanScan). Methods: The pooled data included 1,621 pancreatic adenocarcinoma cases and 1,719 matched controls from twelve cohorts using a nested case-control study design. Subjects who were diagnosed with diabetes near the time (<2 years) of pancreatic cancer diagnosis were excluded from all analyses. All analyses were adjusted for age, race, gender, study, alcohol use, smoking, BMI, and family history of pancreatic cancer. Results: Self-reported diabetes was associated with a forty percent increased risk of pancreatic cancer (OR = 1.40, 95 % CI: 1.07, 1.84). The association differed by duration of diabetes; risk was highest for those with a duration of 2-8 years (OR = 1.79, 95 % CI: 1.25, 2.55); there was no association for those with 9+ years of diabetes (OR = 1.02, 95 % CI: 0.68, 1.52). Conclusions: These findings provide support for a relationship between diabetes and pancreatic cancer risk. The absence of association in those with the longest duration of diabetes may reflect hypoinsulinemia and warrants further investigation.

  • 157. Emaus, Marleen J.
    et al.
    Peeters, Petra H. M.
    Bakker, Marije F.
    Overvad, Kim
    Tjonneland, Anne
    Olsen, Anja
    Romieu, Isabelle
    Ferrari, Pietro
    Dossus, Laure
    Boutron-Ruault, Marie Christine
    Baglietto, Laura
    Fortner, Renee T.
    Kaaks, Rudolf
    Boeing, Heiner
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Masala, Giovanna
    Pala, Valeria
    Panico, Salvatore
    Tumino, Rosario
    Polidoro, Silvia
    Skeie, Guri
    Lund, Eiliv
    Weiderpass, Elisabete
    Ramon Quiros, J.
    Travier, Noemie
    Sanchez, Maria-Jose
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Dorronsoro, Miren
    Winkvist, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Wennberg, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Bueno-de-Mesquita, H. Bas
    Khaw, Kay-Tee
    Travis, Ruth C.
    Key, Timothy J.
    Aune, Dagfinn
    Gunter, Marc
    Riboli, Elio
    van Gils, Carla H.
    Vegetable and fruit consumption and the risk of hormone receptor-defined breast cancer in the EPIC cohort2016Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 103, nr 1, s. 168-177Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The recent literature indicates that a high vegetable intake and not a high fruit intake could be associated with decreased steroid hormone receptor–negative breast cancer risk.

    Objective: This study aimed to investigate the association between vegetable and fruit intake and steroid hormone receptor–defined breast cancer risk.

    Design: A total of 335,054 female participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort were included in this study (mean ± SD age: 50.8 ± 9.8 y). Vegetable and fruit intake was measured by country-specific questionnaires filled out at recruitment between 1992 and 2000 with the use of standardized procedures. Cox proportional hazards models were stratified by age at recruitment and study center and were adjusted for breast cancer risk factors.

    Results: After a median follow-up of 11.5 y (IQR: 10.1–12.3 y), 10,197 incident invasive breast cancers were diagnosed [3479 estrogen and progesterone receptor positive (ER+PR+); 1021 ER and PR negative (ER−PR−)]. Compared with the lowest quintile, the highest quintile of vegetable intake was associated with a lower risk of overall breast cancer (HRquintile 5–quintile 1: 0.87; 95% CI: 0.80, 0.94). Although the inverse association was most apparent for ER−PR− breast cancer (ER−PR−: HRquintile 5–quintile 1: 0.74; 95% CI: 0.57, 0.96; P-trend = 0.03; ER+PR+: HRquintile 5–quintile 1: 0.91; 95% CI: 0.79, 1.05; P-trend = 0.14), the test for heterogeneity by hormone receptor status was not significant (P-heterogeneity = 0.09). Fruit intake was not significantly associated with total and hormone receptor–defined breast cancer risk.

    Conclusion: This study supports evidence that a high vegetable intake is associated with lower (mainly hormone receptor–negative) breast cancer risk.

  • 158. Engeset, D.
    et al.
    Skeie, G.
    Olsen, A.
    Nilsson, Lena Maria
    Umeå universitet, Arktiskt centrum vid Umeå universitet (Arcum). Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Dietary patterns and whole grain in Scandinavia. The HELGA project2013Ingår i: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 63, nr Supplement 1, s. 341-341Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background and objectives: In the recent years a trendwithin nutrition epidemiology has been to assess overall dietaryquality, often by identifying dietary patterns. The HELGAstudy population is based on samples of existing cohorts fromthe three Scandinavian countries. All three cohorts are part ofthe EPIC study. The aim of this study is to find a typical wholegrain pattern in Scandinavia and see if the pattern is similar inthe three countries.Methods: The associations among the variables were investigatedby factor analysis.Results: Both Norway and Sweden had two breakfast patternsand one dinner pattern. Both the countries had a healthybreakfast pattern including food items commonly consideredhealthy, such as fruit, yoghurt and breakfast cereals. However,coarse bread was the main item in a more traditional pattern for Norway, while it was a part of the healthy pattern inSweden. The second breakfast pattern in Sweden included unhealthyitems like white bread, cakes, sweets, soft drinks andalcohol. The dinner pattern was almost equal in Sweden andNorway. Denmark differed from the other Scandinavian countriesconcerning dietary patterns. Only one breakfast patternwas found. This pattern had some similarities with the traditionalNorwegian pattern, but scored high on all whole grainitems while in Norway only wheat had a high score. Two dinnerpatterns are seen for Denmark, the healthier one includesfruit and vegetables, fish and poultry, the second includes meatand meat products, ice cream and alcohol.Conclusions: When comparing dietary patterns from thethree Scandinavian countries, we find both differences andsimilarities. The main whole grain item used in Norway andSweden seems to be wheat, while rye is more dominant in Denmark.

  • 159. Engeset, Dagrun
    et al.
    Braaten, Tonje
    Teucher, Birgit
    Kühn, Tilman
    Bueno-de-Mesquita, H B
    Leenders, Max
    Agudo, Antonio
    Bergmann, Manuela M
    Valanou, Elisavet
    Naska, Androniki
    Trichopoulou, Antonia
    Key, Timothy J
    Crowe, Francesca L
    Overvad, Kim
    Sonestedt, Emily
    Mattiello, Amalia
    Peeters, Petra H
    Wennberg, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Jansson, Jan Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Boutron-Ruault, Marie-Christine
    Dossus, Laure
    Dartois, Laureen
    Li, Kuanrong
    Barricarte, Aurelio
    Ward, Heather
    Riboli, Elio
    Agnoli, Claudia
    Huerta, José María
    Sánchez, María-José
    Tumino, Rosario
    Altzibar, Jone M
    Vineis, Paolo
    Masala, Giovanna
    Ferrari, Pietro
    Muller, David C
    Johansson, Mattias
    Luisa Redondo, M
    Tjønneland, Anne
    Olsen, Anja
    Olsen, Karina Standahl
    Brustad, Magritt
    Skeie, Guri
    Lund, Eiliv
    Fish consumption and mortality in the European Prospective Investigation into Cancer and Nutrition cohort2015Ingår i: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 30, nr 1, s. 57-70Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Fish is a source of important nutrients and may play a role in preventing heart diseases and other health outcomes. However, studies of overall mortality and cause-specific mortality related to fish consumption are inconclusive. We examined the rate of overall mortality, as well as mortality from ischaemic heart disease and cancer in relation to the intake of total fish, lean fish, and fatty fish in a large prospective cohort including ten European countries. More than 500,000 men and women completed a dietary questionnaire in 1992-1999 and were followed up for mortality until the end of 2010. 32,587 persons were reported dead since enrolment. Hazard ratios and their 99 % confidence interval were estimated using Cox proportional hazard regression models. Fish consumption was examined using quintiles based on reported consumption, using moderate fish consumption (third quintile) as reference, and as continuous variables, using increments of 10 g/day. All analyses were adjusted for possible confounders. No association was seen for fish consumption and overall or cause-specific mortality for both the categorical and the continuous analyses, but there seemed to be a U-shaped trend (p < 0.000) with fatty fish consumption and total mortality and with total fish consumption and cancer mortality (p = 0.046).

  • 160. Engeset, Dagrun
    et al.
    Hofoss, Dag
    Nilsson, Lena Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Olsen, Anja
    Tjønneland, Anne
    Skeie, Guri
    Dietary patterns and whole grain cereals in the Scandinavian countries: differences and similarities. The HELGA project2015Ingår i: Public Health Nutrition, ISSN 1368-9800, E-ISSN 1475-2727, Vol. 18, nr 5, s. 905-915Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To identify dietary patterns with whole grains as a main focus to see if there is a similar whole grain pattern in the three Scandinavian countries; Denmark, Sweden and Norway. Another objective is to see if items suggested for a Nordic Food Index will form a typical Nordic pattern when using factor analysis. Setting: The HELGA study population is based on samples of existing cohorts: the Norwegian Women and Cancer Study, the Swedish Vasterbotten cohort and the Danish Diet, Cancer and Health study. The HELGA study aims to generate knowledge about the health effects of whole grain foods. Subjects: The study included a total of 119 913 participants. Design: The associations among food variables from FFQ were investigated by principal component analysis. Only food groups common for all three cohorts were included. High factor loading of a food item shows high correlation of the item to the specific diet pattern. Results: The main whole grain for Denmark and Sweden was rye, while Norway had highest consumption of wheat. Three similar patterns were found: a cereal pattern, a meat pattern and a bread pattern. However, even if the patterns look similar, the food items belonging to the patterns differ between countries. Conclusions: High loadings on breakfast cereals and whole grain oat were common in the cereal patterns for all three countries. Thus, the cereal pattern may be considered a common Scandinavian whole grain pattern. Food items belonging to a Nordic Food Index were distributed between different patterns.

  • 161.
    Englund, Undis
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nilsson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Bucht, Gustaf
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Björnstig, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Pettersson Kymmer, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Physical activity in middle-aged women and hip fracture risk: the UFO study2011Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 22, nr 2, s. 499-505Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Summary: In a population-based case-control study, we demonstrate that middle-aged women who were active with walking or in different physical spare time activities were at lower risk of later sustaining a hip fracture compared to more sedentary women.

    Introduction: In middle-aged women participating in the Umeå Fracture and Osteoporosis (UFO) study, we investigated whether physical activity is associated with a subsequent decreased risk of sustaining a hip fracture.

    Methods: The UFO study is a nested case-control study investigating associations between bone markers, lifestyle, and osteoporotic fractures. We identified 81 female hip fracture cases that had reported lifestyle data before they sustained their fracture. Each case was compared with two female controls who were identified from the same cohort and matched for age and week of reporting data, yielding a total cohort of 237 subjects. Mean age at baseline was 57.2 ± 5.0 years, and mean age at fracture was 65.4 ± 6.4 years.

    Results: Conditional logistic regression analysis with adjustments for height, weight, smoking, and menopausal status showed that subjects who were regularly active with walking or had a moderate or high frequency of physical spare time activities (i.e. berry/mushroom picking and snow shovelling) were at reduced risk of sustaining a hip fracture (OR 0.14; 95% CI; 0.05–0.53 for walking and OR 0.19; 95% CI; 0.08–0.46, OR 0.17, 95% CI; 0.05–0.64 for moderate and high frequency of spare time activities, respectively) compared to more sedentary women.

    Conclusion: An active lifestyle in middle age seems to reduce the risk of future hip fracture. Possible mechanisms may include improved muscle strength, coordination, and balance resulting in a decreased risk of falling and perhaps also direct skeletal benefits.

  • 162.
    Englund, Undis
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nilsson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Bergström, Ulrica
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Pettersson Kymmer, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Active commuting reduces the risk of wrist fractures in middle-aged women: the UFO study2013Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 24, nr 2, s. 533-540Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Middle-aged women with active commuting had significantly lower risk for wrist fracture than women commuting by car/bus.

    INTRODUCTION: Our purpose was to investigate whether a physically active lifestyle in middle-aged women was associated with a reduced risk of later sustaining a low-trauma wrist fracture.

    METHODS: The Umeå Fracture and Osteoporosis (UFO) study is a population-based nested case-control study investigating associations between lifestyle and fragility fractures. From a cohort of ~35,000 subjects, we identified 376 female wrist fracture cases who had reported data regarding their commuting habits, occupational, and leisure physical activity, before they sustained their fracture. Each fracture case was compared with at least one control drawn from the same cohort and matched for age and week of reporting data, yielding a total of 778 subjects. Mean age at baseline was 54.3 ± 5.8 years, and mean age at fracture was 60.3 ± 5.8 years.

    RESULTS: Conditional logistic regression analysis with adjustments for height, body mass index, smoking, and menopausal status showed that subjects with active commuting (especially walking) were at significantly lower risk of sustaining a wrist fracture (OR 0.48; 95 % CI 0.27-0.88) compared with those who commuted by car or bus. Leisure time activities such as dancing and snow shoveling were also associated with a lower fracture risk, whereas occupational activity, training, and leisure walking or cycling were unrelated to fracture risk.

    CONCLUSION: This study suggests that active commuting is associated with a lower wrist fracture risk, in middle-aged women.

  • 163. Engström, Karin S
    et al.
    Wennberg, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Department of Medicine, Skellefteå Hospital, Skellefteå, Sweden.
    Strömberg, Ulf
    Bergdahl, Ingvar A.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lundh, Thomas
    Norberg, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Rentschler, Gerda
    Vessby, Bengt
    Skerfving, Staffan
    Broberg, Karin
    Evaluation of the impact of genetic polymorphisms in glutathione-related genes on the association between methylmercury or n-3 polyunsaturated long chain fatty acids and risk of myocardial infarction: a case-control study2011Ingår i: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 10, s. Article nr 33-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The n-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, which are present in fish, are protective against myocardial infarction. However, fish also contains methylmercury, which influences the risk of myocardial infarction, possibly by generating oxidative stress. Methylmercury is metabolized by conjugation to glutathione, which facilitates elimination. Glutathione is also an antioxidant. Individuals with certain polymorphisms in glutathione-related genes may tolerate higher exposures to methylmercury, due to faster metabolism and elimination and/or better glutathione-associated antioxidative capacity. They would thus benefit more from the protective agents in fish, such as eicosapentaenoic+docosahexaenoic acid and selenium. The objective for this study was to elucidate whether genetic polymorphisms in glutathione-related genes modify the association between eicosapentaenoic+docosahexaenoic acid or methylmercury and risk of first ever myocardial infarction.

    METHODS: Polymorphisms in glutathione-synthesizing (glutamyl-cysteine ligase catalytic subunit, GCLC and glutamyl-cysteine ligase modifier subunit, GCLM) or glutathione-conjugating (glutathione S-transferase P, GSTP1) genes were genotyped in 1027 individuals from northern Sweden (458 cases of first-ever myocardial infarction and 569 matched controls). The impact of these polymorphisms on the association between erythrocyte-mercury (proxy for methylmercury) and risk of myocardial infarction, as well as between plasma eicosapentaenoic+docosahexaenoic acid and risk of myocardial infarction, was evaluated by conditional logistic regression. The effect of erythrocyte-selenium on risk of myocardial infarction was also taken into consideration.

    RESULTS: There were no strong genetic modifying effects on the association between plasma eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury and risk of myocardial infarction risk. When eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury were divided into tertiles, individuals with GCLM-588 TT genotype displayed a lower risk relative to the CC genotype in all but one tertile; in most tertiles the odds ratio was around 0.5 for TT. However, there were few TT carriers and the results were not statistically significant. The results were similar when taking plasma eicosapentaenoic+docosahexaenoic acid, erythrocyte-selenium and erythrocyte-mercury into account simultaneously.

    CONCLUSIONS: No statistically significant genetic modifying effects were seen for the association between plasma eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury and risk of myocardial infarction. Still, our results indicate that the relatively rare GCLM-588 TT genotype may have an impact, but a larger study is necessary for confirmation.

  • 164. Enroth, Stefan
    et al.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Gyllensten, Ulf
    Effects of Long-Term Storage Time and Original Sampling Month on Biobank Plasma Protein Concentrations2016Ingår i: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 12, s. 309-314Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The quality of clinical biobank samples is crucial to their value for life sciences research. A number of factors related to the collection and storage of samples may affect the biomolecular composition. We have studied the effect of long-time freezer storage, chronological age at sampling, season and month of the year and on the abundance levels of 108 proteins in 380 plasma samples collected from 106 Swedish women. Storage time affected 18 proteins and explained 4.8–34.9% of the observed variance. Chronological age at sample collection after adjustment for storage-time affected 70 proteins and explained 1.1–33.5% of the variance. Seasonal variation had an effect on 15 proteins and month (number of sun hours) affected 36 proteins and explained up to 4.5% of the variance after adjustment for storage-time and age. The results show that freezer storage time and collection date (month and season) exerted similar effect sizes as age on the protein abundance levels. This implies that information on the sample handling history, in particular storage time, should be regarded as equally prominent covariates as age or gender and need to be included in epidemiological studies involving protein levels.

  • 165.
    Eriksson, Catharina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Kokkonen, Heidi
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Johansson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Autoantibodies predate the onset of Systemic Lupus Erythematosus in northern Sweden2011Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 13, nr 1, s. R30-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Autoantibodies have a central role in systemic lupus erythematosus (SLE). The presence of autoantibodies preceding disease onset by years has been reported both in patients with SLE and those with rheumatoid arthritis, suggesting a gradual development of these diseases. To identify autoantibodies in a Northern European population predating the onset of symptoms of SLE and their relationship to presenting symptoms.

    METHODS: The register of patients fulfilling the American College of Rheumatology (ACR) criteria for SLE and with a given date for the onset of symptoms was co-analysed with the register of the Medical Biobank, Umea, Sweden. Thirty-eight patients were identified as having donated blood samples prior to symptom onset. A nested case-control study (1:4) was performed with 152 age- and sex-matched controls identified from within the Biobank register. Antibodies against anti- Sjogren's syndrome antigen A (Ro/SSA) (60 and 52 kDa), anti- Sjogren's syndrome antigen B (La/SSB), anti-Smith antibody (Sm), ribonucleoprotein (RNP), scleroderma-70 (Scl-70), anti- histidyl-tRNA synthetase antibody (Jo-1), double-stranded DNA (dsDNA); Centromere protein B and histones were analysed using the anti-nuclear antibody test II (ANA-II) Plus Test System (Athena Multi-Lyte(R)) on a Bio-Plex Array Reader (Luminex200). ANA were analysed using indirect immunofluorescence on Human Epidermal cells-2 (HEp2-cells) at a sample dilution of 1:100.

    RESULTS: Autoantibodies against nuclear antigens were detected 5.6 (+/- 4.7; mean +/- SD) years before the onset of symptoms and 8.7 (+/- 5.6) years before diagnosis in 63% of the individuals who subsequently developed SLE. The sensitivity (45.7%) was highest for ANA with a specificity of 95%, followed by anti-dsDNA and anti-Ro/SSA antibodies both with sensitivities of 20.0% at specificities of 98.7% and 97.4%, respectively. The odds ratio (OR) for anti-dsDNA predicting disease was 18.13 (CI 95%; 3.58-91.84), and for ANA 11.5 (CI 95%; 4.54-28.87). Anti-Ro/SSA antibodies appeared first, 6.6 (+/- 2.5) years prior to symptom onset. The mean number of autoantibodies in pre-diseased individuals was 1.4 and after disease onset 3.1 (P< 0.0005). The time predating disease was shorter, and the number of autoantibodies greater, in those individuals with serositis as a presenting symptom in comparison to those with arthritis and skin manifestations.

    CONCLUSIONS: Autoantibodies against nuclear antigens were detected in individuals developing SLE several years before the onset of symptoms and diagnosis. The most sensitive autoantibodies were ANA, Ro/SSA and dsDNA, with the highest predictive OR for anti-dsDNA antibodies. The first autoantibodies detected were anti-Ro/SSA.

  • 166.
    Eriksson, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Johnson, Owe
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Hellsten, Gideon
    Norsjö District Health Centre, Norsjö; Sweden.
    Nilsson, Torbjörn K
    Department of Clinical Chemistry, Örebro University Hospital, Örebro, Sweden.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Improved fibrinolytic activity during exercise may be an effect of the adipocyte-derived hormones leptin and adiponectin2008Ingår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 122, nr 5, s. 701-708Artikel i tidskrift (Refereegranskat)
    Abstract [en]
    Introduction

    Physical activity is associated with improved fibrinolytic activity and reduced risk for cardiovascular disease. High levels of leptin and low levels of adiponectin, both adipocyte-derived hormones, or adipokines, are related to dysfibrinolysis and risk for cardiovascular disease. In this study, we explored if improved fibrinolytic activity during exercise could be linked to changes in leptin and adiponectin levels.

    Materials and methods

    Twenty healthy men (mean age 36 years) participated in a 14-day long skiing expedition in the Swedish mountains. They were randomly assigned to either a 40% or a 30% fat-based diet. Anthropometry, lipids, fibrinolytic activity (PAI-1 activity, tPA activity and mass) and adipokines (leptin and adiponectin) were measured before, during and six weeks after the expedition.

    Results

    PAI-1 activity and circulating levels of leptin decreased whereas levels of adiponectin increased during exercise. The fall in PAI-1 activity showed a strong linear association with changes in leptin and adiponectin levels (p = 0.001 and p < 0.001, respectively). Changes in leptin and adiponectin levels were independent of decreasing waist circumference. However, the association between anthropometric measures and adipokines changed considerably during the expedition. Adiponectin was weakly and negatively associated with BMI at baseline. In contrast, there was a strong positive association between adiponectin and BMI after two weeks of exercise, whereas the association between leptin and BMI became less pronounced. In addition, increasing leptin and decreasing adiponectin levels were associated with increasing PAI-1 activity during the six weeks following the expedition. After six weeks of normal activity, fibrinolytic activity and hormone levels returned towards baseline levels.

    Conclusion

    Heavy exercise induced improved fibrinolytic activity, which was associated independently with changes in circulating levels of the adipocyte-derived hormones leptin and adiponectin. Improved fibrinolytic activity (and reduced risk for cardiovascular disease) related to physical activity could possibly be mediated by leptin and adiponectin.

  • 167.
    Eriksson, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wennberg, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Jansson, Jan-Håkan
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Weinehall, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Leptin and adiponectin predict independently a first-ever myocardial infarction with a sex difference: data from a large prospective Swedish nested case-referent studyManuskript (preprint) (Övrigt vetenskapligt)
  • 168.
    Eriksson, Marie
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Forslund, Ann-Sofi
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Wennberg, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Eliasson, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Greater decreases in cholesterol levels among individuals with high cardiovascular risk than among the general population: the northern Sweden MONICA study 1994 to 20142016Ingår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 37, nr 25, s. 1985-1992Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM: Decreasing cholesterol levels in Western populations is the main reason for decreasing mortality due to coronary heart disease. Our aim was to analyze trends in cholesterol levels in the population during a period of 20 years in relation to previous cardiovascular disease (CVD), other cardiovascular risk factors, and socioeconomic status.

    METHODS AND RESULTS: A total of 4546 women and 4349 men aged 25-74 years participated in five population-based surveys in the Northern Sweden MONICA Study between 1994 and 2014 (participation rate 76.8-62.5%). Total cholesterol levels decreased from 6.2 mmol/L (95% confidence interval, CI, 6.1-6.2) in 1994 to 5.5 mmol/L (CI 5.4-5.5) in 2014. The decrease was more pronounced in elderly vs. younger participants (1.0 vs. 0.5 mmol/L). In 2014, participants with previous CVD, diabetes, or hypertension had lower cholesterol levels than the general population, whereas their levels were higher or similar to the general population in 1994. The use of lipid-lowering drugs increased markedly and was used by 14.3% in 2014. Previously described differences in cholesterol levels between participants with obesity and normal weight, and between those with and without university education, diminished, or vanished over time.

    CONCLUSION: Cholesterol levels decreased by 0.7 mmol/L over 20 years with no sign of abating. The improvement occurred in all age and gender groups but more prominently among those at high risk of ischaemic heart disease.

  • 169. Erzurumluoglu, A Mesut
    et al.
    Liu, Mengzhen
    Jackson, Victoria E
    Barnes, Daniel R
    Datta, Gargi
    Melbourne, Carl A
    Young, Robin
    Batini, Chiara
    Surendran, Praveen
    Jiang, Tao
    Adnan, Sheikh Daud
    Afaq, Saima
    Agrawal, Arpana
    Altmaier, Elisabeth
    Antoniou, Antonis C
    Asselbergs, Folkert W
    Baumbach, Clemens
    Bierut, Laura
    Bertelsen, Sarah
    Boehnke, Michael
    Bots, Michiel L
    Brazel, David M
    Chambers, John C
    Chang-Claude, Jenny
    Chen, Chu
    Corley, Janie
    Chou, Yi-Ling
    David, Sean P
    de Boer, Rudolf A
    de Leeuw, Christiaan A
    Dennis, Joe G
    Dominiczak, Anna F
    Dunning, Alison M
    Easton, Douglas F
    Eaton, Charles
    Elliott, Paul
    Evangelou, Evangelos
    Faul, Jessica D
    Foroud, Tatiana
    Goate, Alison
    Gong, Jian
    Grabe, Hans J
    Haessler, Jeff
    Haiman, Christopher
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Hammerschlag, Anke R
    Harris, Sarah E
    Hattersley, Andrew
    Heath, Andrew
    Hsu, Chris
    Iacono, William G
    Kanoni, Stavroula
    Kapoor, Manav
    Kaprio, Jaakko
    Kardia, Sharon L
    Karpe, Fredrik
    Kontto, Jukka
    Kooner, Jaspal S
    Kooperberg, Charles
    Kuulasmaa, Kari
    Laakso, Markku
    Lai, Dongbing
    Langenberg, Claudia
    Le, Nhung
    Lettre, Guillaume
    Loukola, Anu
    Luan, Jian'an
    Madden, Pamela A F
    Mangino, Massimo
    Marioni, Riccardo E
    Marouli, Eirini
    Marten, Jonathan
    Martin, Nicholas G
    McGue, Matt
    Michailidou, Kyriaki
    Mihailov, Evelin
    Moayyeri, Alireza
    Moitry, Marie
    Müller-Nurasyid, Martina
    Naheed, Aliya
    Nauck, Matthias
    Neville, Matthew J
    Nielsen, Sune Fallgaard
    North, Kari
    Perola, Markus
    Pharoah, Paul D P
    Pistis, Giorgio
    Polderman, Tinca J
    Posthuma, Danielle
    Poulter, Neil
    Qaiser, Beenish
    Rasheed, Asif
    Reiner, Alex
    Renstrom, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Genetic and Molecular Epidemiology Unit, Lund University.
    Rice, John
    Rohde, Rebecca
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Samani, Nilesh J
    Samuel, Maria
    Schlessinger, David
    Scholte, Steven H
    Scott, Robert A
    Sever, Peter
    Shao, Yaming
    Shrine, Nick
    Smith, Jennifer A
    Starr, John M
    Stirrups, Kathleen
    Stram, Danielle
    Stringham, Heather M
    Tachmazidou, Ioanna
    Tardif, Jean-Claude
    Thompson, Deborah J
    Tindle, Hilary A
    Tragante, Vinicius
    Trompet, Stella
    Turcot, Valerie
    Tyrrell, Jessica
    Vaartjes, Ilonca
    van der Leij, Andries R
    van der Meer, Peter
    Varga, Tibor V
    Verweij, Niek
    Völzke, Henry
    Wareham, Nicholas J
    Warren, Helen R
    Weir, David R
    Weiss, Stefan
    Wetherill, Leah
    Yaghootkar, Hanieh
    Yavas, Ersin
    Jiang, Yu
    Chen, Fang
    Zhan, Xiaowei
    Zhang, Weihua
    Zhao, Wei
    Zhao, Wei
    Zhou, Kaixin
    Amouyel, Philippe
    Blankenberg, Stefan
    Caulfield, Mark J
    Chowdhury, Rajiv
    Cucca, Francesco
    Deary, Ian J
    Deloukas, Panos
    Di Angelantonio, Emanuele
    Ferrario, Marco
    Ferrières, Jean
    Franks, Paul W
    Frayling, Tim M
    Frossard, Philippe
    Hall, Ian P
    Hayward, Caroline
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Department of Public Health and Clinical Medicine, Skellefteå Research Unit, Umeå University, Umeå, Sweden..
    Jukema, J Wouter
    Kee, Frank
    Männistö, Satu
    Metspalu, Andres
    Munroe, Patricia B
    Nordestgaard, Børge Grønne
    Palmer, Colin N A
    Salomaa, Veikko
    Sattar, Naveed
    Spector, Timothy
    Strachan, David Peter
    van der Harst, Pim
    Zeggini, Eleftheria
    Saleheen, Danish
    Butterworth, Adam S
    Wain, Louise V
    Abecasis, Goncalo R
    Danesh, John
    Tobin, Martin D
    Vrieze, Scott
    Liu, Dajiang J
    Howson, Joanna M M
    Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci2019Ingår i: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.

  • 170. Estrada, Karol
    et al.
    Styrkarsdottir, Unnur
    Evangelou, Evangelos
    Hsu, Yi-Hsiang
    Duncan, Emma L
    Ntzani, Evangelia E
    Oei, Ling
    Albagha, Omar ME
    Amin, Najaf
    Kemp, John P
    Koller, Daniel L
    Li, Guo
    Liu, Ching-Ti
    Minster, Ryan L
    Moayyeri, Alireza
    Vandenput, Liesbeth
    Willner, Dana
    Xiao, Su-Mei
    Yerges-Armstrong, Laura M
    Zheng, Hou-Feng
    Alonso, Nerea
    Eriksson, Joel
    Kammerer, Candace M
    Kaptoge, Stephen K
    Leo, Paul J
    Thorleifsson, Gudmar
    Wilson, Scott G
    Wilson, James F
    Aalto, Ville
    Alen, Markku
    Aragaki, Aaron K
    Aspelund, Thor
    Center, Jacqueline R
    Dailiana, Zoe
    Duggan, David J
    Garcia, Melissa
    Garcia-Giralt, Natàlia
    Giroux, Sylvie
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Hocking, Lynne J
    Husted, Lise Bjerre
    Jameson, Karen A
    Khusainova, Rita
    Kim, Ghi Su
    Kooperberg, Charles
    Koromila, Theodora
    Kruk, Marcin
    Laaksonen, Marika
    Lacroix, Andrea Z
    Lee, Seung Hun
    Leung, Ping C
    Lewis, Joshua R
    Masi, Laura
    Mencej-Bedrac, Simona
    Nguyen, Tuan V
    Nogues, Xavier
    Patel, Millan S
    Prezelj, Janez
    Rose, Lynda M
    Scollen, Serena
    Siggeirsdottir, Kristin
    Smith, Albert V
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Trompet, Stella
    Trummer, Olivia
    van Schoor, Natasja M
    Woo, Jean
    Zhu, Kun
    Balcells, Susana
    Brandi, Maria Luisa
    Buckley, Brendan M
    Cheng, Sulin
    Christiansen, Claus
    Cooper, Cyrus
    Dedoussis, George
    Ford, Ian
    Frost, Morten
    Goltzman, David
    González-Macías, Jesús
    Kähönen, Mika
    Karlsson, Magnus
    Khusnutdinova, Elza
    Koh, Jung-Min
    Kollia, Panagoula
    Langdahl, Bente Lomholt
    Leslie, William D
    Lips, Paul
    Ljunggren, Osten
    Lorenc, Roman S
    Marc, Janja
    Mellström, Dan
    Obermayer-Pietsch, Barbara
    Olmos, José M
    Pettersson-Kymmer, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Reid, David M
    Riancho, José A
    Ridker, Paul M
    Rousseau, François
    Lagboom, P Eline S
    Tang, Nelson LS
    Urreizti, Roser
    Van Hul, Wim
    Viikari, Jorma
    Zarrabeitia, María T
    Aulchenko, Yurii S
    Castano-Betancourt, Martha
    Grundberg, Elin
    Herrera, Lizbeth
    Ingvarsson, Thorvaldur
    Johannsdottir, Hrefna
    Kwan, Tony
    Li, Rui
    Luben, Robert
    Medina-Gómez, Carolina
    Th Palsson, Stefan
    Reppe, Sjur
    Rotter, Jerome I
    Sigurdsson, Gunnar
    van Meurs, Joyce BJ
    Verlaan, Dominique
    Williams, Frances MK
    Wood, Andrew R
    Zhou, Yanhua
    Gautvik, Kaare M
    Pastinen, Tomi
    Raychaudhuri, Soumya
    Cauley, Jane A
    Chasman, Daniel I
    Clark, Graeme R
    Cummings, Steven R
    Danoy, Patrick
    Dennison, Elaine M
    Eastell, Richard
    Eisman, John A
    Gudnason, Vilmundur
    Hofman, Albert
    Jackson, Rebecca D
    Jones, Graeme
    Jukema, J Wouter
    Khaw, Kay-Tee
    Lehtimäki, Terho
    Liu, Yongmei
    Lorentzon, Mattias
    McCloskey, Eugene
    Mitchell, Braxton D
    Nandakumar, Kannabiran
    Nicholson, Geoffrey C
    Oostra, Ben A
    Peacock, Munro
    Pols, Huibert AP
    Prince, Richard L
    Raitakari, Olli
    Reid, Ian R
    Robbins, John
    Sambrook, Philip N
    Sham, Pak Chung
    Shuldiner, Alan R
    Tylavsky, Frances A
    van Duijn, Cornelia M
    Wareham, Nick J
    Cupples, L Adrienne
    Econs, Michael J
    Evans, David M
    Harris, Tamara B
    Kung, Annie Wai Chee
    Psaty, Bruce M
    Reeve, Jonathan
    Spector, Timothy D
    Streeten, Elizabeth A
    Zillikens, M Carola
    Thorsteinsdottir, Unnur
    Ohlsson, Claes
    Karasik, David
    Richards, J Brent
    Brown, Matthew A
    Stefansson, Kari
    Uitterlinden, André G
    Ralston, Stuart H
    Ioannidis, John PA
    Kiel, Douglas P
    Rivadeneira, Fernando
    Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture2012Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 44, s. 491-501Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.

  • 171. Eussen, Simone J P M
    et al.
    Vollset, Stein Emil
    Hustad, Steinar
    Midttun, Øivind
    Meyer, Klaus
    Fredriksen, Ase
    Ueland, Per Magne
    Jenab, Mazda
    Slimani, Nadia
    Ferrari, Pietro
    Agudo, Antonio
    Sala, Núria
    Capellá, Gabriel
    Del Giudice, Giuseppe
    Palli, Domenico
    Boeing, Heiner
    Weikert, Cornelia
    Bueno-de-Mesquita, H Bas
    Büchner, Frederike L
    Carneiro, Fátima
    Berrino, Franco
    Vineis, Paolo
    Tumino, Rosario
    Panico, Salvatore
    Berglund, Göran
    Manjer, Jonas
    Stenling, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Martínez, Carmen
    Arrizola, Larraitz
    Barricarte, Aurelio
    Navarro, Carmen
    Rodriguez, Laudina
    Bingham, Sheila
    Linseisen, Jakob
    Kaaks, Rudolf
    Overvad, Kim
    Tjønneland, Anne
    Peeters, Petra H M
    Numans, Mattijs E
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Morois, Sophie
    Trichopoulou, Antonia
    Lund, Eiliv
    Plebani, Mario
    Riboli, Elio
    González, Carlos A
    Vitamins B2 and B6 and genetic polymorphisms related to one-carbon metabolism as risk factors for gastric adenocarcinoma in the European prospective investigation into cancer and nutrition.2010Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 19, nr 1, s. 28-38Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    B vitamins and polymorphisms in genes coding for enzymes involved in one-carbon metabolism may affect DNA synthesis and methylation and thereby be implicated in carcinogenesis. Previous data on vitamins B2 and B6 and genetic polymorphisms other than those involving MTHFR as risk factors for gastric cancer (GC) are sparse and inconsistent. In this case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort, cases (n = 235) and controls (n = 601) were matched for study center, age, sex, and time of blood sampling. B2 and B6 species were measured in plasma, and the sum of riboflavin and flavin mononucleotide was used as the main exposure variable for vitamin B2 status, whereas the sum of pyridoxal 5'-phosphate, pyridoxal, and 4-pyridoxic acid was used to define vitamin B6 status. In addition, we determined eight polymorphisms related to one-carbon metabolism. Relative risks for GC risk were calculated with conditional logistic regression, adjusted for Helicobacter pylori infection status and smoking status. Adjusted relative risks per quartile (95% confidence interval, P(trend)) were 0.85 (0.72-1.01, 0.06) for vitamin B2 and 0.78 (0.65-0.93, <0.01) for vitamin B6. Both relations were stronger in individuals with severe chronic atrophic gastritis. The polymorphisms were not associated with GC risk and did not modify the observed vitamin-cancer associations. In summary, results from this large European cohort study showed an inverse association between vitamin B2 and GC risk, which is borderline significant, and a significant inverse association between vitamin B6 and GC risk.

  • 172.
    Evengård, Birgitta
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar. Umeå universitet, Arktiskt centrum vid Umeå universitet (Arcum).
    Nilsson, Lena Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Arktiskt centrum vid Umeå universitet (Arcum).
    Destouni, Gia
    Stockholms universitet.
    Säker tillgång till mat och vatten prioriterad fråga för Arktis2013Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 110, nr 05, s. CCF7-Artikel i tidskrift (Övrig (populärvetenskap, debatt, mm))
    Abstract [sv]

    Arktis befinner sig i förändring. Dessa förändringar beror på mänskliga aktiviteter i regionen och på den globala klimatförändringen, som märks först och mest i norr till exempel där den sibiriska tundran övergår i gräsbevuxen terräng. Djur och människor som bor i den här delen av världen är redan påverkade av förändringarna och kommer att förbli så under lång tid framöver. Ursprungsbefolkningar runt om i Arktis samlar sig i protester, nu senast i Kanada. De många ursprungsbefolkningarna i Arktis lever ofta nära naturen och är därför mer sårbara än andra, men även samhällen med god infrastruktur påverkas av miljöförändringar. I Sverige märkte vi nyligen detta, när närmare 100 000 personer i Östersund och Skellefteå med omgivningar vintern 2010–2011 fick koka sitt vatten under månader på grund av att en parasit (Cryptosporidium) kom in i vattnet. Olika slags system behöver kontrolleras regelbundet, så att säkra datatolkningar kan ges till beslutsfattare, för att vidta åtgärder i tid för ökad säkerhet.

  • 173. Fawcett, Katherine A
    et al.
    Wheeler, Eleanor
    Morris, Andrew P
    Ricketts, Sally L
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Daly, Allan
    Wasson, Jon
    Permutt, Alan
    Hattersley, Andrew T
    Glaser, Benjamin
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    McCarthy, Mark I
    Wareham, Nicholas J
    Sandhu, Manjinder S
    Barroso, Inês
    Detailed investigation of the role of common and low-frequency WFS1 variants in type 2 diabetes risk2010Ingår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 59, nr 3, s. 741-746Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We identified six highly correlated SNPs that show strong and comparable associations with risk of type 2 diabetes, but further refinement of these associations will require large sample sizes (>100,000) or studies in ethnically diverse populations. Low frequency variants in WFS1 are unlikely to have a large impact on type 2 diabetes risk in white U.K. populations, highlighting the complexities of undertaking association studies with low-frequency variants identified by resequencing.

  • 174. Fedirko, Veronika
    et al.
    Riboli, Elio
    Bueno-de-Mesquita, H Bas
    Rinaldi, Sabina
    Pischon, Tobias
    Norat, Teresa
    Jansen, Eugène H J M
    van Duijnhoven, Fränzel J B
    Tjønneland, Anne
    Olsen, Anja
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Françoise
    Engel, Pierre
    Kaaks, Rudolf
    Teucher, Birgit
    Boeing, Heiner
    Buijsse, Brian
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Lagiou, Pagona
    Sieri, Sabina
    Vineis, Paolo
    Panico, Salvatore
    Palli, Domenico
    Tumino, Rosario
    van Gils, Carla H
    Peeters, Petra H M
    Chirlaque, Maria-Dolores
    Gurrea, Aurelio Barricarte
    Rodríguez, Laudina
    Molina-Montes, Esther
    Dorronsoro, Miren
    Bonet, Catalina
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Key, Timothy J
    Tsilidis, Konstantinos K
    Khaw, Kay-Tee
    Romieu, Isabelle
    Straif, Kurt
    Wark, Petra A
    Romaguera, Dora
    Jenab, Mazda
    Prediagnostic circulating parathyroid hormone concentration and colorectal cancer in the European Prospective Investigation into Cancer and Nutrition cohort2011Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 20, nr 5, s. 767-778Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Parathyroid hormone (PTH) has been proposed to play a promoting role in carcinogenesis. However, no epidemiologic studies have yet directly investigated its role in colorectal cancer (CRC).

    METHODS: A case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort was conducted with 1,214 incident, sporadic CRC cases matched to 1,214 controls. Circulating prediagnostic PTH and 25-hydroxy vitamin D [25(OH)D] concentrations were measured by enzyme-linked immunosorbent assays. Detailed dietary and lifestyle questionnaire data were collected at baseline. Multivariable conditional logistic regression was used to estimate the incidence rate ratio (RR) with 95% confidence intervals (95% CI) for the association between circulating PTH and CRC risk.

    RESULTS: In multivariate analyses [including adjustment for 25(OH)D concentration] with a priori defined cutoff points, high levels of serum PTH (≥65 ng/L) compared with medium PTH levels of 30-65 ng/L were associated with increased CRC risk (RR = 1.41, 95% CI: 1.03-1.93). In analyses by sex, the CRC risk was 1.77 (95% CI: 1.14-2.75) and 1.15 (95% CI: 0.73-1.84) in men and women, respectively (P(heterogeneity) = 0.01). In subgroup analyses by anatomical subsite, the risk for colon cancer was RR = 1.56, 95% CI: 1.03-2.34, and for rectal cancer RR = 1.20, 95% CI: 0.72-2.01 (P(heterogeneity) = 0.21). Effect modification by various risk factors was examined.

    CONCLUSIONS: The results of this study suggest that high serum PTH levels may be associated with incident, sporadic CRC in Western European populations, and in particular among men.

    IMPACT: To our knowledge, this is the first study on PTH and CRC. The role of PTH in carcinogenesis needs to be further investigated.

  • 175. Fedirko, Veronika
    et al.
    Riboli, Elio
    Tjønneland, Anne
    Ferrari, Pietro
    Olsen, Anja
    Bueno-de-Mesquita, H Bas
    van Duijnhoven, Fränzel J B
    Norat, Teresa
    Jansen, Eugène H J M
    Dahm, Christina C
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Françoise
    Racine, Antoine
    Lukanova, Annekatrin
    Teucher, Birgit
    Boeing, Heiner
    Aleksandrova, Krasimira
    Trichopoulou, Antonia
    Benetou, Vassiliki
    Trichopoulos, Dimitrios
    Grioni, Sara
    Vineis, Paolo
    Panico, Salvatore
    Palli, Domenico
    Tumino, Rosario
    Siersema, Peter D
    Peeters, Petra H
    Skeie, Guri
    Brustad, Magritt
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Quirós, Jose Ramón
    Sánchez, Maria José
    Dorronsoro, Miren
    Bonet, Catalina
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Key, Timothy J
    Crowe, Francesca
    Khaw, Kay-Tee
    Wareham, Nick
    Romieu, Isabelle
    McKay, James
    Wark, Petra A
    Romaguera, Dora
    Jenab, Mazda
    Prediagnostic 25-Hydroxyvitamin D, VDR and CASR polymorphisms, and survival in patients with colorectal cancer in Western European populations2012Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 21, nr 4, s. 582-593Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Individuals with higher blood 25-hydroxyvitamin D [25(OH)D] levels have a lower risk of developing colorectal cancer (CRC), but the influence of 25(OH)D on mortality after CRC diagnosis is unknown.

    Methods: The association between prediagnostic 25(OH)D levels and CRC-specific (N ¼ 444) and overall mortality (N ¼ 541) was prospectively examined among 1,202 participants diagnosed with CRC between 1992 and 2003 in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.Multivariable Cox proportional hazards models were used to calculate HRs and corresponding 95% CIs according to 25(OH)D quintiles and genetic variation within the VDR and CASR genes. Potential dietary, lifestyle, and metabolic effect modifiers were also investigated.

    Results: There were 541 deaths, 444 (82%) due to CRC. Mean follow-up was 73 months. In multivariable analysis, higher 25(OH)D levels were associated with a statistically significant reduction in CRC-specific (Ptrend ¼ 0.04) and overall mortality (Ptrend ¼ 0.01). Participants with 25(OH)D levels in the highest quintile had an adjusted HR of 0.69 (95% CI: 0.50–0.93) for CRC-specific mortality and 0.67 (95% CI: 0.50–0.88) for overall mortality, compared with the lowest quintile. Except for a possible interaction by prediagnostic dietary calcium intake (Pinteraction ¼ 0.01), no other potential modifying factors related to CRC survival were noted. The VDR (FokI and BsmI) and CASR (rs1801725) genotypes were not associated with survival.

    Conclusions: High prediagnostic 25(OH)D levels are associated with improved survival of patients with CRC. 

    Impact: Our findings may stimulate further research directed at investigating the effects of blood vitamin D levels before, at, and after CRC diagnosis on outcomes in CRC patients.

  • 176. Feitosa, Mary F.
    et al.
    Kraja, Aldi T.
    Chasman, Daniel I.
    Sung, Yun J.
    Winkler, Thomas W.
    Ntalla, Ioanna
    Guo, Xiuqing
    Franceschini, Nora
    Cheng, Ching-Yu
    Sim, Xueling
    Vojinovic, Dina
    Marten, Jonathan
    Musani, Solomon K.
    Li, Changwei
    Bentley, Amy R.
    Brown, Michael R.
    Schwander, Karen
    Richard, Melissa A.
    Noordam, Raymond
    Aschard, Hugues
    Bartz, Traci M.
    Bielak, Lawrence F.
    Dorajoo, Rajkumar
    Fisher, Virginia
    Hartwig, Fernando P.
    Horimoto, Andrea R. V. R.
    Lohman, Kurt K.
    Manning, Alisa K.
    Rankinen, Tuomo
    Smith, Albert V.
    Tajuddin, Salman M.
    Wojczynski, Mary K.
    Alver, Maris
    Boissel, Mathilde
    Cai, Qiuyin
    Campbell, Archie
    Chai, Jin Fang
    Chen, Xu
    Divers, Jasmin
    Gao, Chuan
    Goel, Anuj
    Hagemeijer, Yanick
    Harris, Sarah E.
    He, Meian
    Hsu, Fang-Chi
    Jackson, Anne U.
    Kahonen, Mika
    Kasturiratne, Anuradhani
    Komulainen, Pirjo
    Kuhnel, Brigitte
    Laguzzi, Federica
    Luan, Jian'an
    Matoba, Nana
    Nolte, Ilja M.
    Padmanabhan, Sandosh
    Riaz, Muhammad
    Rueedi, Rico
    Robino, Antonietta
    Said, M. Abdullah
    Scott, Robert A.
    Sofer, Tamar
    Stancakova, Alena
    Takeuchi, Fumihiko
    Tayo, Bamidele O.
    van der Most, Peter J.
    Varga, Tibor V.
    Vitart, Veronique
    Wang, Yajuan
    Ware, Erin B.
    Warren, Helen R.
    Weiss, Stefan
    Wen, Wanqing
    Yanek, Lisa R.
    Zhang, Weihua
    Zhao, Jing Hua
    Afaq, Saima
    Amin, Najaf
    Amini, Marzyeh
    Arking, Dan E.
    Aung, Tin
    Boerwinkle, Eric
    Borecki, Ingrid
    Broeckel, Ulrich
    Brown, Morris
    Brumat, Marco
    Burke, Gregory L.
    Canouil, Mickael
    Chakravarti, Aravinda
    Charumathi, Sabanayagam
    Chen, Yii-Der Ida
    Connell, John M.
    Correa, Adolfo
    Fuentes, Lisa de las
    de Mutsert, Renee
    de Silva, H. Janaka
    Deng, Xuan
    Ding, Jingzhong
    Duan, Qing
    Eaton, Charles B.
    Ehret, Georg
    Eppinga, Ruben N.
    Evangelou, Evangelos
    Fau, Jessica D.
    Felix, Stephan B.
    Forouhi, Nita G.
    Forrester, Terrence
    Franco, Oscar H.
    Friedlander, Yechiel
    Gandin, Ilaria
    Gao, He
    Ghanbari, Mohsen
    Gigante, Bruna
    Gu, C. Charles
    Gu, Dongfeng
    Hagenaars, Saskia P.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Harris, Tamara B.
    He, Jiang
    Heikkinen, Sami
    Heng, Chew-Kiat
    Hirata, Makoto
    Howard, Barbara V.
    Ikram, M. Arfan
    John, Ulrich
    Katsuya, Tomohiro
    Khor, Chiea Chuen
    Kilpelainen, Tuomas O.
    Koh, Woon-Puay
    Krieger, Jose E.
    Kritchevsky, Stephen B.
    Kubo, Michiaki
    Kuusisto, Johanna
    Lakka, Timo A.
    Langefeld, Carl D.
    Langenberg, Claudia
    Launer, Lenore J.
    Lehne, Benjamin
    Lewis, Cora E.
    Li, Yize
    Lin, Shiow
    Liu, Jianjun
    Liu, Jingmin
    Loh, Marie
    Louie, Tin
    Magi, Reedik
    McKenzie, Colin A.
    Meitinger, Thomas
    Metspalu, Andres
    Milaneschi, Yuri
    Milani, Lili
    Mohlke, Karen L.
    Momozawa, Yukihide
    Nalls, Mike A.
    Nelson, Christopher P.
    Sotoodehnia, NelsonNona
    Norris, Jill M.
    O'Connell, Jeff R.
    Palmer, Nicholette D.
    Perls, Thomas
    Pedersen, Nancy L.
    Peters, Annette
    Peyser, Patricia A.
    Poulter, Neil
    Raffel, Leslie J.
    Raitakari, Olli T.
    Roll, Kathryn
    Rose, Lynda M.
    Rosendaal, Frits R.
    Rotter, Jerome I.
    Schmidt, Carsten O.
    Schreiner, Pamela J.
    Schupf, Nicole
    Scott, William R.
    Sever, Peter S.
    Shi, Yuan
    Sidney, Stephen
    Sims, Mario
    Sitlani, Colleen M.
    Smith, Jennifer A.
    Snieder, Harold
    Starr, John M.
    Strauch, Konstantin
    Stringham, Heather M.
    Tan, Nicholas Y. Q.
    Tang, Hua
    Taylor, Kent D.
    Teo, Yik Ying
    Tham, Yih Chung
    Turner, Stephen T.
    Uitterlinden, Andre G.
    Vollenweider, Peter
    Waldenberger, Melanie
    Wang, Lihua
    Wang, Ya Xing
    Bin Wei, Wen
    Williams, Christine
    Yao, Jie
    Yu, Caizheng
    Yuan, Jian-Min
    Zhao, Wei
    Zonderman, Alan B.
    Becker, Diane M.
    Boehnke, Michael
    Bowden, Donald W.
    Chambers, John C.
    Deary, Ian J.
    Esko, Tonu
    Farrall, Martin
    Franks, Paul W.
    Freedman, Barry I.
    Froguel, Philippe
    Gasparini, Paolo
    Gieger, Christian
    Jonas, Jost Bruno
    Kamatani, Yoichiro
    Kato, Norihiro
    Kooner, Jaspal S.
    Kutalik, Zoltan
    Laakso, Markku
    Laurie, Cathy C.
    Leander, Karin
    Lehtimaki, Terho
    Study, Lifelines Cohort
    Magnusson, Patrik K. E.
    Oldehinkel, Albertine J.
    Penninx, Brenda W. J. H.
    Poiasek, Ozren
    Porteous, David J.
    Rauramaa, Rainer
    Samani, Nilesh J.
    Scott, James
    Shu, Xiao-Ou
    van der Harst, Pim
    Wagenknecht, Lynne E.
    Wareham, Nicholas J.
    Watkins, Hugh
    Weir, David R.
    Wickremasinghe, Ananda R.
    Wu, Tangchun
    Zheng, Wei
    Bouchard, Claude
    Christensen, Kaare
    Evans, Michele K.
    Gudnason, Vilmundur
    Horta, Bernardo L.
    Kardia, Sharon L. R.
    Liu, Yongmei
    Pereira, Alexandre C.
    Psaty, Bruce M.
    Ridker, Paul M.
    van Dam, Rob M.
    Gauderman, W. James
    Zhu, Xiaofeng
    Mook-Kanamori, Dennis O.
    Fornage, Myriam
    Rotimi, Charles N.
    Cupples, L. Adrienne
    Kelly, Tanika N.
    Fox, Ervin R.
    Hayward, Caroline
    van Duijn, Cornelia M.
    Tai, E. Shyong
    Wong, Tien Yin
    Kooperberg, Charles
    Palmas, Walter
    Rice, Kenneth
    Morrison, Alanna C.
    Elliott, Paul
    Caulfield, Mark J.
    Munroe, Patricia B.
    Rao, Dabeeru C.
    Province, Michael A.
    Levy, Daniel
    Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries2018Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 6, artikel-id e0198166Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

  • 177. Ferrari, P
    et al.
    McKay, JD
    Jenab, M
    Brennan, P
    Canzian, F
    Vogel, U
    Tjonneland, A
    Overvad, K
    Tolstrup, JS
    Boutron-Ruault, M-C
    Clavel-Chapelon, F
    Morois, S
    Kaaks, R
    Boeing, H
    Bergmann, M
    Trichopoulou, A
    Katsoulis, M
    Trichopoulos, D
    Krogh, V
    Panico, S
    Sacerdote, C
    Palli, D
    Tumino, R
    Peeters, PH
    van Gils, CH
    Bueno-de-Mesquita, B
    Vrieling, A
    Lund, E
    Hjartaker, A
    Agudo, A
    Suarez, LR
    Arriola, L
    Chirlaque, M-D
    Ardanaz, E
    Sanchez, M-J
    Manjer, J
    Lindkvist, B
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Allen, N
    Key, T
    Khaw, K-T
    Slimani, N
    Rinaldi, S
    Romieu, I
    Boffetta, P
    Romaguera, D
    Norat, T
    Riboli, E
    Alcohol dehydrogenase and aldehyde dehydrogenase gene polymorphisms, alcohol intake and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study2012Ingår i: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 66, nr 12, s. 1303-1308Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND/OBJECTIVES: Heavy alcohol drinking is a risk factor of colorectal cancer (CRC), but little is known on the effect of polymorphisms in the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) on the alcohol-related risk of CRC in Caucasian populations.

    SUBJECTS/METHODS: A nested case-control study (1269 cases matched to 2107controls by sex, age, study centre and date of blood collection) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the impact of rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms on CRC risk. Using the wild-type variant of each polymorphism as reference category, CRC risk estimates were calculated using conditional logistic regression, with adjustment for matching factors.

    RESULTS: Individuals carrying one copy of the rs1229984(A) (ADH1B) allele (fast metabolizers) showed an average daily alcohol intake of 4.3 g per day lower than subjects with two copies of the rs1229984(G) allele (slow metabolizers) (P-diff<0.01). None of the polymorphisms was associated with risk of CRC or cancers of the colon or rectum. Heavy alcohol intake was more strongly associated with CRC risk among carriers of the rs1573496(C) allele, with odds ratio equal to 2.13 (95% confidence interval: 1.26-3.59) compared with wild-type subjects with low alcohol consumption P-((interaction)=0.07).

    CONCLUSIONS: The rs1229984(A) (ADH1B) allele was associated with a reduction in alcohol consumption. The rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms were not associated with CRC risk overall in Western-European populations. However, the relationship between alcohol and CRC risk might be modulated by the rs1573496 (ADH7) polymorphism. European Journal of Clinical Nutrition (2012) 66, 1303-1308; doi: 10.1038/ejcn.2012.173; published online 14 November 2012

  • 178. Ferrari, P
    et al.
    Roddam, A
    Fahey, M T
    Jenab, M
    Bamia, C
    Ocké, M
    Amiano, P
    Hjartåker, A
    Biessy, C
    Rinaldi, S
    Huybrechts, I
    Tjønneland, A
    Dethlefsen, C
    Niravong, M
    Clavel-Chapelon, F
    Linseisen, J
    Boeing, H
    Oikonomou, E
    Orfanos, P
    Palli, D
    Santucci de Magistris, M
    Bueno-de-Mesquita, H B
    Peeters, P H M
    Parr, C L
    Braaten, T
    Dorronsoro, M
    Berenguer, T
    Gullberg, B
    Johansson, I
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Welch, A A
    Riboli, E
    Bingham, S
    Slimani, N
    A bivariate measurement error model for nitrogen and potassium intakes to evaluate the performance of regression calibration in the European Prospective Investigation into Cancer and Nutrition study.2009Ingår i: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 63 Suppl 4, nr 4, s. S179-87Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study suggests that 24-HDRs can be used as reference measurements at the individual and aggregate levels for potassium intake, whereas, for nitrogen intake, good performance is observed for between-centre calibration, but some limitations are apparent at the individual level.

  • 179. Ferrari, Pietro
    et al.
    Al-Delaimy, Wael K
    Slimani, Nadia
    Boshuizen, Hendriek C
    Roddam, Andrew
    Orfanos, Philippos
    Skeie, Guri
    Rodriguez-Barranco, Miguel
    Thiebaut, Anne
    Johansson, Gerd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Palli, Domenico
    Boeing, Heiner
    Overvad, Kim
    Riboli, Elio
    An approach to estimate between- and within-group correlation coefficients in multicenter studies: plasma carotenoids as biomarkers of intake of fruits and vegetables2005Ingår i: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 162, nr 6, s. 591-598Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In a multicenter study, the overall correlation between two variables can be broken down into a within- and a between-group correlation reflecting associations at the individual and aggregate levels, respectively. A random-effects model is used to estimate variance components of nutrition-related variables and the within- and between-group correlation coefficients. Using data from the European Prospective Investigation into Cancer and Nutrition (EPIC), the authors analyzed the association between levels of three plasma carotenoids (alpha-carotene, beta-cryptoxanthin, and lycopene) and dietary intake of three items (total fruits, carrots, and tomatoes), assessed through dietary questionnaire and single 24-hour dietary recall measurements, in a cross-sectional study involving 3,089 subjects from nine European countries. Intraclass correlation coefficients were 0.178 for alpha-carotene, 0.216 for beta-cryptoxanthin, and 0.299 for lycopene. The between-group correlation coefficients were higher than the within-group coefficients for all three carotenoids. For beta-cryptoxanthin and fruit intake, the between-group versus the within-group correlations were 0.78 and 0.26 for the dietary questionnaire and 0.85 and 0.19 for the 24-hour dietary recall. Results indicate that variability of exposure is driven mainly by the individual compared with the aggregate variation and that biomarker levels perform fairly accurately in discriminating population-level consumption of fruits and vegetables.

  • 180. Fiskesund, Roland
    et al.
    Stegmayr, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Vikström, Max
    Weinehall, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    de Faire, Ulf
    Frostegård, Johan
    Low levels of antibodies against phosphorylcholine predict development of stroke in a population-based study from northern Sweden2010Ingår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 41, nr 4, s. 607-612Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND PURPOSE: Natural immunoglobulin M antibodies specific for phosphorylcholine (anti-PC) have been implicated in atherosclerosis. We have shown previously that high levels of anti-PC predict a slower progression of atherosclerosis in humans and that low levels of anti-PC are associated with higher risk for cardiovascular disease. Here we determine the association between anti-PC and the incidence of stroke. METHODS: Using a nested case control study design, we examined 227 incident cases (125 men and 102 women) of first-time stroke and 455 age- and sex-matched controls identified during a 13-year time period (1985 to 1999) within the population-based cohorts of the Västerbotten Intervention Project (VIP) and the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease (WHO MONICA) project in Northern Sweden. Odds ratios of stroke with 95% CIs with adjustments for age, gender, smoking, serum cholesterol, diabetes, body mass index, and blood pressure were determined. Anti-PC levels were measured using ELISA. RESULTS: A significant association between low levels of anti-PC at baseline and incident stroke was seen for the whole group of anti-PC levels below the 30th percentile (multivariately adjusted odds ratio, 1.62; CI, 1.11 to 2.35). Analyses of gender-specific associations indicated fairly strong associations for females, especially at the lowest 30th percentile (multivariately adjusted odds ratio, 2.65; CI, 1.41 to 4.95). No associations were noted for men. CONCLUSION: Low anti-PC is a novel independent risk marker for development of stroke. Measurements of anti-PC could be used to identify immunodeficient subjects at an increased risk for stroke. The possibility that such subjects might be targets for novel modes of treatment such as immunotherapies deserves further investigation.

  • 181. Fontaine-Bisson, B
    et al.
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Payne, F
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Barroso, I
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Evaluating the discriminative power of multi-trait genetic risk scores for type 2 diabetes in a northern Swedish population.2010Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 53, nr 10, s. 2155-2162Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS/HYPOTHESIS: We determined whether single nucleotide polymorphisms (SNPs) previously associated with diabetogenic traits improve the discriminative power of a type 2 diabetes genetic risk score. METHODS: Participants (n = 2,751) were genotyped for 73 SNPs previously associated with type 2 diabetes, fasting glucose/insulin concentrations, obesity or lipid levels, from which five genetic risk scores (one for each of the four traits and one combining all SNPs) were computed. Type 2 diabetes patients and non-diabetic controls (n = 1,327/1,424) were identified using medical records in addition to an independent oral glucose tolerance test. RESULTS: Model 1, including only SNPs associated with type 2 diabetes, had a discriminative power of 0.591 (p < 1.00 x 10(-20) vs null model) as estimated by the area under the receiver operator characteristic curve (ROC AUC). Model 2, including only fasting glucose/insulin SNPs, had a significantly higher discriminative power than the null model (ROC AUC 0.543; p = 9.38 x 10(-6) vs null model), but lower discriminative power than model 1 (p = 5.92 x 10(-5)). Model 3, with only lipid-associated SNPs, had significantly higher discriminative power than the null model (ROC AUC 0.565; p = 1.44 x 10(-9)) and was not statistically different from model 1 (p = 0.083). The ROC AUC of model 4, which included only obesity SNPs, was 0.557 (p = 2.30 x 10(-7) vs null model) and smaller than model 1 (p = 0.025). Finally, the model including all SNPs yielded a significant improvement in discriminative power compared with the null model (p < 1.0 x 10(-20)) and model 1 (p = 1.32 x 10(-5)); its ROC AUC was 0.626. CONCLUSIONS/INTERPRETATION: Adding SNPs previously associated with fasting glucose, insulin, lipids or obesity to a genetic risk score for type 2 diabetes significantly increases the power to discriminate between people with and without clinically manifest type 2 diabetes compared with a model including only conventional type 2 diabetes loci.

  • 182. Fortner, Renee T.
    et al.
    Huesing, Anika
    Kuehn, Tilman
    Konar, Meric
    Overvad, Kim
    Tjonneland, Anne
    Hansen, Louise
    Boutron-Ruault, Marie-Christine
    Severi, Gianluca
    Fournier, Agnes
    Boeing, Heiner
    Trichopoulou, Antonia
    Benetou, Vasiliki
    Orfanos, Philippos
    Masala, Giovanna
    Agnoli, Claudia
    Mattiello, Amalia
    Tumino, Rosario
    Sacerdote, Carlotta
    Bueno-de-Mesquita, H. B(as)
    Peeters, Petra H. M.
    Weiderpass, Elisabete
    Gram, Inger T.
    Gavrilyuk, Oxana
    Ramon Quiros, J.
    Maria Huerta, Jose
    Ardanaz, Eva
    Larranaga, Nerea
    Lujan-Barroso, Leila
    Sanchez-Cantalejo, Emilio
    Butt, Salma Tuna
    Borgquist, Signe
    Idahl, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Khaw, Kay-Tee
    Allen, Naomi E.
    Rinaldi, Sabina
    Dossus, Laure
    Gunter, Marc
    Merritt, Melissa A.
    Tzoulaki, Ioanna
    Riboli, Elio
    Kaaks, Rudolf
    Endometrial cancer risk prediction including serum-based biomarkers: results from the EPIC cohort2017Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 140, nr 6, s. 1317-1323Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Endometrial cancer risk prediction models including lifestyle, anthropometric and reproductive factors have limited discrimina-tion. Adding biomarker data to these models may improve predictive capacity; to our knowledge, this has not been investigat-ed for endometrial cancer. Using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we investigated the improvement in discrimination gained by adding serum biomarker concentrations to risk estimates derived from an existing risk prediction model based on epidemiologic factors. Serum concentrations of sex steroid hormones, metabolic markers, growth factors, adipokines and cytokines were evaluated in a step-wise backward selec-tion process; biomarkers were retained at p < 0.157 indicating improvement in the Akaike information criterion (AIC). Improvement in discrimination was assessed using the C-statistic for all biomarkers alone, and change in C-statistic from addition of biomarkers to preexisting absolute risk estimates. We used internal validation with bootstrapping (1000-fold) to adjust for over-fitting. Adiponectin, estrone, interleukin-1 receptor antagonist, tumor necrosis factor-alpha and triglycerides were select-ed into the model. After accounting for over-fitting, discrimination was improved by 2.0 percentage points when all evaluated biomarkers were included and 1.7 percentage points in the model including the selected biomarkers. Models including eti-ologic markers on independent pathways and genetic markers may further improve discrimination.

  • 183. Fortner, Renee T.
    et al.
    Tolockiene, Egle
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Schock, Helena
    Oda, Husam
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Lakso, Hans-Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Kaaks, Rudolf
    Toniolo, Paolo
    Zeleniuch-Jacquotte, Anne
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Early pregnancy sex steroids during primiparous pregnancies and maternal breast cancer: a nested case-control study in the Northern Sweden Maternity Cohort2017Ingår i: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 19, artikel-id 82Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Pregnancy and parity are associated with subsequent breast cancer risk. Experimental and epidemiologic data suggest a role for pregnancy sex steroid hormones.

    Methods: We conducted a nested case–control study in the Northern Sweden Maternity Cohort (1975–2007). Eligible women had provided a blood sample in the first 20 weeks of gestation during a primiparous pregnancy leading to a term delivery. The current study includes 223 cases and 417 matched controls (matching factors: age at and date of blood collection). Estrogen receptor (ER) and progesterone receptor (PR) status was available for all cases; androgen receptor (AR) data were available for 41% of cases (n = 92). Sex steroids were quantified by high-performance liquid chromatography tandem mass spectrometry. Odds ratios (ORs) and 95% confidence intervals were estimated using conditional logistic regression.

    Results: Higher concentrations of circulating progesterone in early pregnancy were inversely associated with ER+/PR+ breast cancer risk (ORlog2: 0.64 (0.41–1.00)). Higher testosterone was positively associated with ER+/PR+ disease risk (ORlog2: 1.57 (1.13–2.18)). Early pregnancy estrogens were not associated with risk, except for relatively high estradiol in the context of low progesterone (split at median, relative to low concentrations of both; OR: 1.87 (1.11–3.16)). None of the investigated hormones were associated with ER–/PR– disease, or with AR+ or AR+/ER+/PR+ disease.

    Conclusions: Consistent with experimental models, high progesterone in early pregnancy was associated with lower risk of ER+/PR+ breast cancer in the mother. High circulating testosterone in early pregnancy, which likely reflects nonpregnant premenopausal exposure, was associated with higher risk of ER+/PR+ disease.

  • 184. Fortner, Renée T
    et al.
    Schock, Helena
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Kaaks, Rudolf
    Lehtinen, Matti
    Pukkala, Eero
    Lakso, Hans-Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Tanner, Minna
    Kallio, Raija
    Joensuu, Heikki
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Zeleniuch-Jacquotte, Anne
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Toniolo, Paolo
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Surcel, Helja-Marja
    Early pregnancy sex steroids and maternal breast cancer: a nested case-control study2014Ingår i: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 74, nr 23, s. 6958-6967Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Pregnancy, parity, and circulating steroid hormone levels are associated with risk of breast cancer, but little is known about hormone concentrations during pregnancy and subsequent breast cancer risk. We evaluated early pregnancy (<140 days gestation) serum estradiol, estrone, progesterone, and testosterone and breast cancer risk in a nested case-control study in the Finnish Maternity Cohort. The cohort includes 98% of pregnancies registered in Finland since 1983. Individuals with samples collected in the first pregnancy leading to a live birth were eligible. Breast cancer cases (n = 1,199) were identified through linkage with the Finnish Cancer Registry; 2,281 matched controls were selected using incidence density sampling. ORs were calculated using conditional logistic regression. Hormone concentrations were not associated with breast cancer overall. Estradiol was positively associated with risk of breast cancer diagnosed age <40 [4th vs. 1st quartile OR 1.60 (1.07-2.39); Ptrend = 0.01], and inversely associated with breast cancer diagnosed at age ≥40 [4th vs. 1st quartile OR 0.71 (0.51-1.00); Ptrend = 0.02]. Elevated concentrations of the steroid hormones were associated with increased risk of estrogen receptor (ER)- and progesterone receptor (PR)-negative tumors in women age <40 at diagnosis. We observed no association between steroid hormones and ER(+)/PR(+) disease. These data suggest a positive association between high concentrations of early pregnancy steroid hormones and risk of ER(-)/PR(-) breast cancer in women diagnosed age <40, and an inverse association for overall breast cancer diagnosed age ≥40. Further research on pregnancy hormones and risk of steroid receptor-negative cancers is needed to further characterize this association.

  • 185. Fortner, Renée T
    et al.
    Schock, Helena
    Kaaks, Rudolf
    Lehtinen, Matti
    Pukkala, Eero
    Lakso, Hans-Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Tanner, Minna
    Kallio, Raija
    Joensuu, Heikki
    Korpela, Jaana
    Toriola, Adetunji T
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Zeleniuch-Jacquotte, Anne
    Toniolo, Paolo
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Surcel, Heljä-Marja
    Human Chorionic Gonadotropin Does Not Correlate with Risk for Maternal Breast Cancer: Results from the Finnish Maternity Cohort2017Ingår i: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 77, nr 1, s. 134-141Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Human chorionic gonadotropin (hCG) is necessary for the maintenance of early pregnancy and promotes normal breast cell differentiation. Administered hCG reduces risk of carcinogen-induced breast cancer in animal models, and higher circulating hCG concentrations were associated with significantly lower long-term risk of breast cancer in a prior nested case-control study. In this study, we investigated early-pregnancy hCG concentrations and subsequent breast cancer risk. We conducted a nested case-control study with 1,191 cases and 2,257 controls (matched on age and date at blood collection) in the Finnish Maternity Cohort, a cohort with serum samples from 98% of pregnancies registered in Finland since 1983. This study included women with a serum sample collected early (<140 days gestation) in their first pregnancy resulting in a live, term birth. Breast cancer cases were identified via the Finnish Cancer Registry. Age at breast cancer diagnosis ranged from 22 to 58 years (mean: 41 years). hCG was measured using a solid-phase competitive chemiluminescence assay. Odds ratios (OR) were calculated using conditional logistic regression. We observed no association between hCG and breast cancer risk, overall [Quartile 4 vs. 1, OR, 1.14; 95% confidence interval (CI), 0.94-1.39], by estrogen and progesterone receptor status, or by ages at first-term birth or diagnosis. Associations did not differ by time between pregnancy and diagnosis (e.g., <5 years, ORQ4 vs. Q1, 1.10; 95% CI, 0.64-1.89; ≥15 years, ORQ4 vs. Q1, 1.36; 95% CI, 0.86-2.13; pheterogeneity = 0.62). This large prospective study does not support an inverse relationship between early pregnancy serum hCG concentrations and breast cancer risk. 

  • 186. Fortner, Renée T.
    et al.
    Schock, Helena
    Le Cornet, Charlotte
    Hüsing, Anika
    Vitonis, Allison F.
    Johnson, Theron S.
    Fichorova, Raina N.
    Fashemi, Titilayo
    Yamamoto, Hidemi S.
    Tjonneland, Anne
    Hansen, Louise
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Kvaskoff, Marina
    Severi, Gianluca
    Boeing, Heiner
    Trichopoulou, Antonia
    Papatesta, Eleni-Maria
    La Vecchia, Carlo
    Palli, Domenico
    Sieri, Sabina
    Tumino, Rosario
    Sacerdote, Carlotta
    Mattiello, Amalia
    Onland-Moret, N. Charlotte
    Peeters, Petra H.
    Bueno-de-Mesquita, H. B(as)
    Weiderpass, Elisabete
    Quirós, J. Ramón
    Duell, Eric J.
    Sánchez, Maria-Jose
    Navarro, Carmen
    Ardanaz, Eva
    Larrañaga, Nerea
    Nodin, Björn
    Jirström, Karin
    Idahl, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Khaw, Kay-Tee
    Travis, Ruth C.
    Gunter, Marc
    Johansson, Mattias
    Dossus, Laure
    Merritt, Melissa A.
    Riboli, Elio
    Terry, Kathryn L.
    Cramer, Daniel W.
    Kaaks, Rudolf
    Ovarian cancer early detection by circulating CA125 in the context of anti-CA125 autoantibody levels: Results from the EPIC cohort2018Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 142, nr 7, s. 1355-1360Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    CA125 is the best ovarian cancer early detection marker to date; however, sensitivity is limited and complementary markers are required to improve discrimination between ovarian cancer cases and non-cases. Anti-CA125 autoantibodies are observed in circulation. Our objective was to evaluate whether these antibodies (1) can serve as early detection markers, providing evidence of an immune response to a developing tumor, and (2) modify the discriminatory capacity of CA125 by either masking CA125 levels (resulting in lower discrimination) or acting synergistically to improve discrimination between cases and non-cases. We investigated these objectives using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (EPIC) including 250 cases diagnosed within 4 years of blood collection and up to four matched controls. Circulating CA125 antigen and antibody levels were quantified using an electrochemiluminescence assay. Adjusted areas under the curve (aAUCs) by 2-year lag-time intervals were calculated using conditional logistic regression calibrated toward the absolute risk estimates from a pre-existing epidemiological risk model as an offset-variable. Anti-CA125 levels alone did not discriminate cases from controls. For cases diagnosed <2 years after blood collection, discrimination by CA125 antigen was suggestively higher with higher anti-CA125 levels (aAUC, highest antibody tertile: 0.84 [0.76-0.92]; lowest tertile: 0.76 [0.67-0.86]; p(het)=0.06). We provide the first evidence of potentially synergistic discrimination effects of CA125 and anti-CA125 antibodies in ovarian early detection. If these findings are replicated, evaluating CA125 in the context of its antibody may improve ovarian cancer early detection. What's new? Although CA125, a mucin produced in epithelial cells, is a known marker for ovarian cancer, complementary biomarkers are necessary for reliable early cancer detection. Here, the authors examined autoantibodies against CA125 as potential pre-diagnosis markers. Although anti-CA125 levels did not discriminate between ovarian cases and controls, discrimination of CA125 differed by levels of its antibody, with the highest discrimination among women with the highest antibody levels. The authors propose that CA125 and anti-CA125 may act synergistically for ovarian cancer early detection.

  • 187. Franceschi, Silvia
    et al.
    Lise, Mauro
    Trépo, Christian
    Berthillon, Pascale
    Chuang, Shu-Chun
    Nieters, Alexandra
    Travis, Ruth C
    Vermeulen, Roel
    Overvad, Kim
    Tjønneland, Anne
    Olsen, Anja
    Bergmann, Manuela M
    Boeing, Heiner
    Kaaks, Rudolf
    Becker, Nikolaus
    Trichopoulou, Antonia
    Lagiou, Pagona
    Bamia, Christina
    Palli, Domenico
    Sieri, Sabina
    Panico, Salvatore
    Tumino, Rosario
    Sacerdote, Carlotta
    Bueno-de-Mesquita, Bas
    Peeters, Petra HM
    Rodríguez, Laudina
    Barroso, Leila Luján
    Dorronsoro, Miren
    Sánchez, María-José
    Navarro, Carmen
    Barricarte, Aurelio
    Regnér, Sara
    Borgquist, Signe
    Melin, Beatrice
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Khaw, Kay-Tee
    Wareham, Nick
    Rinaldi, Sabina
    Hainaut, Pierre
    Riboli, Elio
    Vineis, Paolo
    Infection with hepatitis B and C viruses and risk of lymphoid malignancies in the European Prospective Investigation into Cancer and Nutrition (EPIC)2011Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 20, nr 1, s. 208-214Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Chronic HBV infection may increase the risk of lymphoid malignancies among healthy European volunteers. Impact: Treatment directed at control of HBV infection should be evaluated in HBsAg-seropositive patients with lymphoid tissue malignancies. Cancer Epidemiol Biomarkers Prev; 20(1); 208-14. ©2011 AACR.

  • 188.
    Franks, Paul
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Medicin.
    Rolandsson, Olov
    Allmänmedicin.
    Debenham, S L
    Fawcett, K A
    Payne, F
    Dina, C
    Froguel, P
    Mohlke, K L
    Willer, C
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Medicin.
    Wareham, N J
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Barroso, I
    Sandhu, M S
    Replication of the association between variants in WFS1 and risk of type 2 diabetes in European populations.2008Ingår i: Diabetologia, ISSN 0012-186X, Vol. 51, nr 3, s. 458-63Artikel i tidskrift (Refereegranskat)
  • 189. Freisling, Heinz
    et al.
    Fahey, Michael T
    Moskal, Aurelie
    Ocké, Marga C
    Ferrari, Pietro
    Jenab, Mazda
    Norat, Teresa
    Naska, Androniki
    Welch, Ailsa A
    Navarro, Carmen
    Schulz, Mandy
    Wirfält, Elisabet
    Casagrande, Corinne
    Amiano, Pilar
    Ardanaz, Eva
    Parr, Christine
    Engeset, Dagrun
    Grioni, Sara
    Sera, Francesco
    Bueno-de-Mesquita, Bas
    van der Schouw, Yvonne T
    Touvier, Mathilde
    Boutron-Ruault, Marie-Christine
    Halkjaer, Jytte
    Dahm, Christina C
    Khaw, Kay-Tee
    Crowe, Francesca
    Linseisen, Jakob
    Kröger, Janine
    Huybrechts, Inge
    Deharveng, Geneviève
    Manjer, Jonas
    Ågren, Åsa
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Trichopoulou, Antonia
    Tsiotas, Kostas
    Riboli, Elio
    Bingham, Sheila
    Slimani, Nadia
    Region-specific nutrient intake patterns exhibit a geographical gradient within and between European countries.2010Ingår i: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 140, nr 7, s. 1280-6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Until recently, the study of nutrient patterns was hampered at an international level by a lack of standardization of both dietary methods and nutrient databases. We aimed to describe the diversity of nutrient patterns in the European Prospective Investigation into Cancer and Nutrition (EPIC) study at population level as a starting point for future nutrient pattern analyses and their associations with chronic diseases in multi-center studies. In this cross-sectional study, 36,034 persons aged 35-74 y were administered a single, standardized 24-h dietary recall. Intake of 25 nutrients (excluding intake from dietary supplements) was estimated using a standardized nutrient database. We used a graphic presentation of mean nutrient intakes by region and sex relative to the overall EPIC means to contrast patterns within and between 10 European countries. In Mediterranean regions, including Greece, Italy, and the southern centers of Spain, the nutrient pattern was dominated by relatively high intakes of vitamin E and monounsaturated fatty acids (MUFA), whereas intakes of retinol and vitamin D were relatively low. In contrast, in Nordic countries, including Norway, Sweden, and Denmark, reported intake of these same nutrients resulted in almost the opposite pattern. Population groups in Germany, The Netherlands, and the UK shared a fatty acid pattern of relatively high intakes of PUFA and SFA and relatively low intakes of MUFA, in combination with a relatively high intake of sugar. We confirmed large variability in nutrient intakes across the EPIC study populations and identified 3 main region-specific patterns with a geographical gradient within and between European countries.

  • 190. Fretts, Amanda M.
    et al.
    Follis, Jack L.
    Nettleton, Jennifer A.
    Lemaitre, Rozenn N.
    Ngwa, Julius S.
    Wojczynski, Mary K.
    Kalafati, Ioanna Panagiota
    Varga, Tibor V.
    Frazier-Wood, Alexis C.
    Houston, Denise K.
    Lahti, Jari
    Ericson, Ulrika
    van den Hooven, Edith H.
    Mikkilae, Vera
    Kiefte-de Jong, Jessica C.
    Mozaffarian, Dariush
    Rice, Kenneth
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Department of Clinical Sciences Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden.
    North, Kari E.
    McKeown, Nicola M.
    Feitosa, Mary F.
    Kanoni, Stavroula
    Smith, Caren E.
    Garcia, Melissa E.
    Tiainen, Anna-Maija
    Sonestedt, Emily
    Manichaikul, Ani
    van Rooij, Frank J. A.
    Dimitriou, Maria
    Raitakari, Olli
    Pankow, James S.
    Djousse, Luc
    Province, Michael A.
    Hu, Frank B.
    Lai, Chao-Qiang
    Keller, Margaux F.
    Peraelae, Mia-Maria
    Rotter, Jerome I.
    Hofman, Albert
    Graff, Misa
    Kaehoenen, Mika
    Mukamal, Kenneth
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Ordovas, Jose M.
    Liu, Yongmei
    Maennistoe, Satu
    Uitterlinden, Andre G.
    Deloukas, Panos
    Seppaelae, Ilkka
    Psaty, Bruce M.
    Cupples, L. Adrienne
    Borecki, Ingrid B.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Clinical Sciences Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA.
    Arnett, Donna K.
    Nalls, Mike A.
    Eriksson, Johan G.
    Orho-Melander, Marju
    Franco, Oscar H.
    Lehtimaeki, Terho
    Dedoussis, George V.
    Meigs, James B.
    Siscovick, David S.
    Consumption of meat is associated with higher fasting glucose and insulin concentrations regardless of glucose and insulin genetic risk scores: a meta-analysis of 50,345 Caucasians2015Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 102, nr 5, s. 1266-1278Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Recent studies suggest that meat intake is associated with diabetes-related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown. Objective: We investigated the associations of meat intake and the interaction of meat with genotype on fasting glucose and insulin concentrations in Caucasians free of diabetes mellitus. Design: Fourteen studies that are part of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium participated in the analysis. Data were provided for up to 50,345 participants. Using linear regression within studies and a fixed-effects meta-analysis across studies, we examined l) the associations of processed meat and unprocessed red meat intake with fasting glucose and insulin concentrations; and 2) the interactions of processed meat and unprocessed red meat with genetic risk score related to fasting glucose or insulin resistance on fasting glucose and insulin concentrations. Results: Processed meat was associated with higher fasting glucose, and unprocessed red meat was associated with both higher fasting glucose and fasting insulin concentrations after adjustment for potential confounders [not including body mass index (BMI)]. For every additional 50-g serving of processed meat per day, fasting glucose was 0.021 mmol/L (95% CI: 0.011, 0.030 mmol/L) higher. Every additional 100-g serving of unprocessed red meat per day was associated with a 0.037-mmol/L (95% CI: 0.023, 0.051-mmol/L) higher fasting glucose concentration and a 0.049-1n-pmon (95% CI: 0.035, 0.063-1n-pmol/L) higher fasting insulin concentration. After additional adjustment for BMI, observed associations were attenuated and no longer statistically significant. The association of processed meat and fasting insulin did not reach statistical significance after correction for multiple comparisons. Observed associations were not modified by genetic loci known to influence fasting glucose or insulin resistance. Conclusion: The association of higher fasting glucose and insulin concentrations with meat consumption was not modified by an index of glucose- and insulin-related single-nucleotide polymorphisms.

  • 191. Fritz, Josef
    et al.
    Bjørge, Tone
    Nagel, Gabriele
    Manjer, Jonas
    Engeland, Anders
    Häggström, Christel
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Concin, Hans
    Teleka, Stanley
    Tretli, Steinar
    Gylling, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Lang, Alois
    Stattin, Pär
    Stocks, Tanja
    Ulmer, Hanno
    The triglyceride-glucose index as a measure of insulin resistance and risk of obesity-related cancers2019Ingår i: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, s. 1-12, artikel-id dyz053Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The role of insulin resistance as a mediator in the association of body mass index (BMI) with site-specific cancer risk has, to our knowledge, never been systematically quantified.

    METHODS: Altogether 510 471 individuals from six European cohorts, with a mean age of 43.1 years, were included. We used the triglyceride glucose product (TyG index) as a surrogate measure for insulin resistance. We fitted Cox models, adjusted for relevant confounders, to investigate associations of TyG index with 10 common obesity-related cancers, and quantified the proportion of the effect of BMI mediated through TyG index on the log-transformed hazard ratio (HR) scale.

    RESULTS: During a median follow-up of 17.2 years, 16 052 individuals developed obesity-related cancers. TyG index was associated with the risk of cancers of the kidney HR per one standard deviation increase 1.13, 95% confidence interval: 1.07 to 1.20], liver (1.13, 1.04 to 1.23), pancreas (1.12, 1.06 to 1.19), colon (1.07, 1.03 to 1.10) and rectum (1.09, 1.04 to 1.14). Substantial proportions of the effect of BMI were mediated by TyG index for cancers of the pancreas (42%), rectum (34%) and colon (20%); smaller proportions for kidney (15%) and liver (11%). Little or no mediation was observed for breast (postmenopausal), endometrial and ovarian cancer. Results were similar for males and females, except for pancreatic cancer where the proportions mediated were 20% and 91%, respectively.

    CONCLUSIONS: The TyG index was associated with increased risk of cancers of the digestive system and substantially mediated the effect of BMI, suggesting that insulin resistance plays a promoting role in the pathogenesis of gastrointestinal cancers.

  • 192. Försti, A
    et al.
    Lei, H
    Tavelin, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Onkologi.
    Enquist, K
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. Patologi.
    Altieri, A
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Hemminki, K
    Lenner, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Onkologi.
    Polymorphisms in the genes of the urokinase plasminogen activation system in relation to colorectal cancer.2007Ingår i: Ann Oncol, ISSN 0923-7534, Vol. 18, s. 1990-1994Artikel i tidskrift (Refereegranskat)
  • 193. Försti, Asta
    et al.
    Jin, Qianren
    Altieri, Andrea
    Johansson, Robert
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Onkologi.
    Wagner, Kerstin
    Enquist, Kerstin
    Grzybowska, Ewa
    Pamula, Jolanta
    Pekala, Wioletta
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Lenner, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Onkologi.
    Hemminki, Kari
    Polymorphisms in the KDR and POSTN genes: association with breast cancer susceptibility and prognosis.2007Ingår i: Breast Cancer Research and Treatment, ISSN 0167-6806, Vol. 101, nr 1, s. 83-93Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: High iron levels can increase the formation of noxious oxygen radicals, which are thought to contribute to cerebrovascular disease. The aim of this prospective study was to determine if iron status and HFE genotypes constitute risk factors for stroke. Methods: First-ever stroke cases (231 ischemic and 42 hemorrhagic) and matched double referents from the population-based Northern Sweden cohorts were studied in a nested case-referent setting. Results: For total iron binding capacity, an increased risk of ischemic stroke was seen in the highest quartile (OR 1.80; 95% CI 1.14-2.83; p for trend 0.012). The highest quartile of transferrin iron saturation showed a decreased risk of ischemic stroke in men (OR 0.44; 95% CI 0.22-0.87; p for trend 0.028), but not in women. There was an increased risk of hemorrhagic stroke in the second (OR 4.07; 95% CI 1.09-15.20) and third quartile (OR 4.22; 95% CI 1.08-16.42) of ferritin. Neither quartiles of plasma iron concentrations nor the HFE C282Y and H63D genotypes were associated with ischemic or hemorrhagic stroke. Conclusions: Iron stores were not positively related to increased risk of ischemic stroke. Furthermore, HFE genotypes did not influence the risk of ischemic or hemorrhagic stroke. Copyright (c) 2007 S. Karger AG, Basel.

  • 194.
    Försti, Asta
    et al.
    Department of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany / Center for Primary Health Care Research, Clinical Research Center, Lund University, Malmö, Sweden.
    Li, Xuchen
    Department of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
    Wagner, Kerstin
    Department of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
    Tavelin, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Enquist, Kerstin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Altieri, Andrea
    Department of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Hemminki, Kari
    Department of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany / Center for Primary Health Care Research, Clinical Research Center, Lund University, Malmö, Sweden.
    Lenner, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Polymorphisms in the transforming growth factor beta 1 pathway in relation to colorectal cancer progression2010Ingår i: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 49, nr 3, s. 270-281Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Transforming growth factor beta1 (TGFB1) acts as a growth inhibitor of normal colonic epithelial cells, however, as a tumor promoter of colorectal cancer (CRC) cells. To explore the association between genetic polymorphisms in the TGFB1 pathway and CRC susceptibility and clinical outcome, we carried out a case-control study on a Swedish population of 308 CRC cases and 585 age- and gender-matched controls. The cases were sampled prospectively and had up to 16 years follow-up, making the study material particularly suitable for survival analysis. On the basis of their reported or predicted functional effect, nine single-nucleotide polymorphisms (TGFB1: Leu10Pro; TGFBR1: 9A/6A and IVS7G+24A; FURIN: C-229T; THBS1: T+42C; LTBP1L: C-256G; LTBP4: T-893G and Thr750Ala; BAMBI: T-779A) were selected for genotyping. We evaluated the associations between genotypes and CRC and Dukes' stage. Survival probabilities were compared between different subgroups. The observed statistically significant associations included a decreased CRC risk for TGFBR1 IVS7G+24A minor allele carriers (odds ratio (OR): 0.72, 95% confidence interval (CI): 0.53-0.97), less aggressive tumors with Dukes' stage A+B for carriers of LTBP4 Thr750Ala and BAMBI T-779A minor alleles (OR: 0.58, 95%CI: 0.36-0.93 and OR: 0.51, 95%CI: 0.29-0.89, respectively) and worse survival for FURIN C-229T heterozygotes (hazard ratio: 1.63, 95%CI: 1.08-2.46). As this is the first study about the influence of the polymorphisms in the TGFB1 pathway on CRC progression, further studies in large independent cohorts are warranted.

  • 195. Gallo, Valentina
    et al.
    Bueno-De-Mesquita, H Bas
    Vermeulen, Roel
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Kyrozis, Andreas
    Linseisen, Jakob
    Kaaks, Rudolph
    Allen, Naomi E
    Roddam, Andrew W
    Boshuizen, Hendriek C
    Peeters, Petra H
    Palli, Domenico
    Mattiello, Amalia
    Sieri, Sabina
    Tumino, Rosario
    Jiménez-Martín, Juan-Manuel
    Díaz, María José Tormo
    Suarez, Laudina Rodriguez
    Trichopoulou, Antonia
    Agudo, Antonio
    Arriola, Larraitz
    Barricante-Gurrea, Aurelio
    Bingham, Sheila
    Khaw, Kay-Tee
    Manjer, Jonas
    Lindkvist, Björn
    Overvad, Kim
    Bach, Flemming W
    Tjønneland, Anne
    Olsen, Anja
    Bergmann, Manuela M
    Boeing, Heiner
    Clavel-Chapelon, Francoise
    Lund, Eiliv
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Middleton, Lefkos
    Vineis, Paolo
    Riboli, Elio
    Smoking and risk for amyotrophic lateral sclerosis: analysis of the EPIC cohort2009Ingår i: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 65, nr 4, s. 378-385Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Cigarette smoking has been reported as "probable" risk factor for Amyotrophic Lateral Sclerosis (ALS), a poorly understood disease in terms of aetiology. The extensive longitudinal data of the European Prospective Investigation into Cancer and Nutrition (EPIC) were used to evaluate age-specific mortality rates from ALS and the role of cigarette smoking on the risk of dying from ALS.

    Methods: A total of 517,890 healthy subjects were included, resulting in 4,591,325 person-years. ALS cases were ascertained through death certificates. Cox hazard models were built to investigate the role of smoking on the risk of ALS, using packs/years and smoking duration to study dose-response.

    Results: A total of 118 subjects died from ALS, resulting in a crude mortality rate of 2.69 per 100,000/year. Current smokers at recruitment had an almost two-fold increased risk of dying from ALS compared to never smokers (HR = 1.89, 95% C.I. 1.14-3.14), while former smokers at the time of enrollment had a 50% increased risk (HR = 1.48, 95% C.I. 0.94-2.32). The number of years spent smoking increased the risk of ALS (p for trend = 0.002). Those who smoked more than 33 years had more than a two-fold increased risk of ALS compared with never smokers (HR = 2.16, 95% C.I. 1.33-3.53). Conversely, the number of years since quitting smoking was associated with a decreased risk of ALS compared with continuing smoking.

    Interpretation: These results strongly support the hypothesis of a role of cigarette smoking in aetiology of ALS. We hypothesize that this could occur through lipid peroxidation via formaldehyde exposure.

  • 196. Gallo, Valentina
    et al.
    Mackenbach, Johan P.
    Ezzati, Majid
    Menvielle, Gwenn
    Kunst, Anton E.
    Rohrmann, Sabine
    Kaaks, Rudolf
    Teucher, Birgit
    Boeing, Heiner
    Bergmann, Manuela M.
    Tjonneland, Anne
    Dalton, Susanne O.
    Overvad, Kim
    Redondo, Maria-Luisa
    Agudo, Antonio
    Daponte, Antonio
    Arriola, Larraitz
    Navarro, Carmen
    Barricante Gurrea, Aurelio
    Khaw, Kay-Tee
    Wareham, Nick
    Key, Tim
    Naska, Androniki
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Masala, Giovanna
    Panico, Salvatore
    Contiero, Paolo
    Tumino, Rosario
    Bueno-de-Mesquita, H. Bas
    Siersema, Peter D.
    Peeters, Petra P.
    Zackrisson, Sophia
    Almquist, Martin
    Eriksson, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Skeie, Guri
    Braaten, Tonje
    Lund, Eiliv
    Illner, Anne-Kathrin
    Mouw, Traci
    Riboli, Elio
    Vineis, Paolo
    Social Inequalities and Mortality in Europe: Results from a Large Multi-National Cohort2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 7, s. e39013-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Socio-economic inequalities in mortality are observed at the country level in both North America and Europe. The purpose of this work is to investigate the contribution of specific risk factors to social inequalities in cause-specific mortality using a large multi-country cohort of Europeans. Methods: A total of 3,456,689 person/years follow-up of the European Prospective Investigation into Cancer and Nutrition (EPIC) was analysed. Educational level of subjects coming from 9 European countries was recorded as proxy for socioeconomic status (SES). Cox proportional hazard model's with a step-wise inclusion of explanatory variables were used to explore the association between SES and mortality; a Relative Index of Inequality (RII) was calculated as measure of relative inequality. Results: Total mortality among men with the highest education level is reduced by 43% compared to men with the lowest (HR 0.57, 95% C.I. 0.52-0.61); among women by 29% (HR 0.71, 95% C.I. 0.64-0.78). The risk reduction was attenuated by 7% in men and 3% in women by the introduction of smoking and to a lesser extent (2% in men and 3% in women) by introducing body mass index and additional explanatory variables (alcohol consumption, leisure physical activity, fruit and vegetable intake) (3% in men and 5% in women). Social inequalities were highly statistically significant for all causes of death examined in men. In women, social inequalities were less strong, but statistically significant for all causes of death except for cancer-related mortality and injuries. Discussion: In this European study, substantial social inequalities in mortality among European men and women which cannot be fully explained away by accounting for known common risk factors for chronic diseases are reported.

  • 197. Gallo, Valentina
    et al.
    Neasham, David
    Airoldi, Luisa
    Ferrari, Pietro
    Jenab, Mazda
    Boffetta, Paolo
    Overvad, Kim
    Tjønneland, Anne
    Clavel-Chapelon, Francoise
    Boeing, Heiner
    Pala, Valeria
    Palli, Domenico
    Panico, Salvatore
    Tumino, Rosario
    Arriola, Larraitz
    Lund, Eiliv
    Bueno-De-Mesquita, Bas
    Peeters, Petra H
    Melander, Olle
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Riboli, Elio
    Saracci, Rodolfo
    Vineis, Paolo
    Second-hand smoke, cotinine levels, and risk of circulatory mortality in a large cohort study of never-smokers2010Ingår i: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 21, nr 2, s. 207-214Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:: Exposure to second-hand smoke has been shown to be associated with increased cardiovascular mortality in several, but not all, epidemiologic studies. Our aim was to investigate the risk of circulatory death associated with exposure to second-hand smoke in never-smokers in a very large prospective study, the European Prospective Investigation into Cancer and Nutrition. A secondary aim was to use cotinine levels for cross-validating self-reported second-hand smoke exposure. METHODS:: Cox proportional hazard models were used to investigate the risk of death due to circulatory causes associated with second-hand smoke exposure in 135,233 never-smokers. Exposure to second-hand smoke was assessed through a questionnaire at enrollment and then validated against plasma cotinine measurements in a subsample. RESULTS:: Study participants who reported second-hand smoke exposure at home had higher cotinine levels (median plasma cotinine concentration in exposed = 0.82 mug/L; in those unexposed 0.02 mug/L). Second-hand smoke exposure at home was associated with an increased risk of dying from cardiovascular diseases (hazard ratio [HR] = 1.38 [95% confidence interval = 1.01-1.90]), all circulatory diseases (1.28 [0.98-1.69]), and coronary heart disease (1.31 [0.83-2.08]) after adjustment for age, sex, education, physical activity, and body mass index. Dose-response relationships were observed between exposure to second-hand smoke at home and risk of circulatory death (HR per each additional hour/d = 1.25 [1.04-1.50]). Having a partner who smokes more than 30 cigarettes per day considerably increased the risk of a circulatory death (2.94 [1.11-7.78]). Second-hand smoke exposure at home was not associated with total mortality (1.03 [0.93-1.13]). DISCUSSION:: Exposure to second-hand smoke at home (as confirmed by plasma cotinine levels) increases the risk of cardiovascular mortality.

  • 198. Gallo, Valentina
    et al.
    Wark, Petra A.
    Jenab, Mazda
    Pearce, Neil
    Brayne, Carol
    Vermeulen, Roel
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hallmans, Goran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Kyrozis, Andreas
    Vanacore, Nicola
    Vahdaninia, Mariam
    Grote, Verena
    Kaaks, Rudolf
    Mattiello, Amalia
    Bueno-de-Mesquita, H. Bas
    Peeters, Petra H.
    Travis, Ruth C.
    Petersson, Jesper
    Hansson, Oskar
    Arriola, Larraitz
    Jimenez-Martin, Juan-Manuel
    Tjonneland, Anne
    Halkjaer, Jytte
    Agnoli, Claudia
    Sacerdote, Carlotta
    Bonet, Catalina
    Trichopoulou, Antonia
    Gavrila, Diana
    Overvad, Kim
    Weiderpass, Elisabete
    Palli, Domenico
    Ramon Quiros, J.
    Tumino, Rosario
    Khaw, Kay-Tee
    Wareham, Nicholas
    Barricante-Gurrea, Aurelio
    Fedirko, Veronika
    Ferrari, Pietro
    Clavel-Chapelon, Francoise
    Boutron-Ruault, Marie-Christine
    Boeing, Heiner
    Vigl, Matthaeus
    Middleton, Lefkos
    Riboli, Elio
    Vineis, Paolo
    Prediagnostic body fat and risk of death from amyotrophic lateral sclerosis The EPIC cohort2013Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 80, nr 9, s. 829-838Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: The aim of this study was to investigate for the first time the association between body fat and risk of amyotrophic lateral sclerosis (ALS) with an appropriate prospective study design. Methods: The EPIC (European Prospective Investigation into Cancer and Nutrition) study included 518,108 individuals recruited from the general population across 10 Western European countries. At recruitment, information on lifestyle was collected and anthropometric characteristics were measured. Cox hazard models were fitted to investigate the associations between anthropometric measures and ALS mortality. Results: Two hundred twenty-two ALS deaths (79 men and 143 women) occurred during the follow-up period (mean follow-up = 13 years). There was a statistically significant interaction between categories of body mass index and sex regarding ALS risk (p = 0.009): in men, a significant linear decrease of risk per unit of body mass index was observed (hazard ratio = 0.93, 95% confidence interval 0.86-0.99 per kg/m(2)); among women, the risk was more than 3-fold increased for underweight compared with normal-weight women. Among women, a significant risk reduction increasing the waist/hip ratio was also evident: women in the top quartile had less than half the risk of ALS compared with those in the bottom quartile (hazard ratio = 0.48, 95% confidence interval 0.25-0.93) with a borderline significant p value for trend across quartiles (p = 0.056). Conclusion: Increased prediagnostic body fat is associated with a decreased risk of ALS mortality. Neurology (R) 2013; 80: 829-838

  • 199. Ge, Wenzhen
    et al.
    Clendenen, Tess V.
    Afanasyeva, Yelena
    Koenig, Karen L.
    Agnoli, Claudia
    Brinton, Louise A.
    Dorgan, Joanne F.
    Eliassen, A. Heather
    Falk, Roni T.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Hankinson, Susan E.
    Hoffman-Bolton, Judith
    Key, Timothy J.
    Krogh, Vittorio
    Nichols, Hazel B.
    Sandler, Dale P.
    Schoemaker, Minouk J.
    Sluss, Patrick M.
    Sund, Malin
    Department of Surgery, Umeå University Hospital, Umeå, Sweden.
    Swerdlow, Anthony J.
    Visvanathan, Kala
    Liu, Mengling
    Zeleniuch-Jacquotte, Anne
    Circulating anti-Müllerian hormone and breast cancer risk: a study in ten prospective cohorts2018Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 142, nr 11, s. 2215-2226Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A strong positive association has been observed between circulating anti‐Müllerian hormone (AMH), a biomarker of ovarian reserve, and breast cancer risk in three prospective studies. Confirming this association is important because of the paucity of biomarkers of breast cancer risk in premenopausal women. We conducted a consortium study including ten prospective cohorts that had collected blood from premenopausal women. A nested case–control design was implemented within each cohort. A total of 2,835 invasive (80%) and in situ (20%) breast cancer cases were individually matched to controls (n = 3,122) on age at blood donation. AMH was measured using a high sensitivity enzyme‐linked immunoabsorbent assay. Conditional logistic regression was applied to the aggregated dataset. There was a statistically significant trend of increasing breast cancer risk with increasing AMH concentration (ptrend across quartiles <0.0001) after adjusting for breast cancer risk factors. The odds ratio (OR) for breast cancer in the top vs. bottom quartile of AMH was 1.60 (95% CI = 1.31–1.94). Though the test for interaction was not statistically significant (pinteraction = 0.15), the trend was statistically significant only for tumors positive for both estrogen receptor (ER) and progesterone receptor (PR): ER+/PR+: ORQ4–Q1 = 1.96, 95% CI = 1.46–2.64, ptrend <0.0001; ER+/PR−: ORQ4–Q1 = 0.82, 95% CI = 0.40–1.68, ptrend = 0.51; ER−/PR+: ORQ4–Q1 = 3.23, 95% CI = 0.48–21.9, ptrend = 0.26; ER−/PR−: ORQ4–Q1 = 1.15, 95% CI = 0.63–2.09, ptrend = 0.60. The association was observed for both pre‐ (ORQ4–Q1= 1.35, 95% CI = 1.05–1.73) and post‐menopausal (ORQ4–Q1 = 1.61, 95% CI = 1.03–2.53) breast cancer (pinteraction = 0.34). In this large consortium study, we confirmed that AMH is associated with breast cancer risk, with a 60% increase in risk for women in the top vs. bottom quartile of AMH.

    What's new? To make informed decisions about screening and prevention, women need tools to accurately assess their breast cancer risk. Young women have few predictive biomarkers to look to; estrogen and progesterone are only weakly predictive before menopause. Anti-Müllerian hormone (AMH), which strongly correlates with age at menopause, may also correlate with breast cancer risk, according to some previous data. Here, the authors test this correlation by conducting nested case-control studies within ten different cohorts. They found that breast cancer risk increased along with increasing AMH concentration, confirming this hormone as a possible biomarker for breast cancer.

  • 200. Georgiadis, Panagiotis
    et al.
    Hebels, Dennie G
    Valavanis, Ioannis
    Liampa, Irene
    Bergdahl, Ingvar A
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Palli, Domenico
    Chadeau-Hyam, Marc
    Chatziioannou, Aristotelis
    Jennen, Danyel G J
    Krauskopf, Julian
    Jetten, Marlon J
    Kleinjans, Jos C S
    Vineis, Paolo
    Kyrtopoulos, Soterios A
    Omics for prediction of environmental health effects: Blood leukocyte-based cross-omic profiling reliably predicts diseases associated with tobacco smoking.2016Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikel-id 20544Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The utility of blood-based omic profiles for linking environmental exposures to their potential health effects was evaluated in 649 individuals, drawn from the general population, in relation to tobacco smoking, an exposure with well-characterised health effects. Using disease connectivity analysis, we found that the combination of smoking-modified, genome-wide gene (including miRNA) expression and DNA methylation profiles predicts with remarkable reliability most diseases and conditions independently known to be causally associated with smoking (indicative estimates of sensitivity and positive predictive value 94% and 84%, respectively). Bioinformatics analysis reveals the importance of a small number of smoking-modified, master-regulatory genes and suggest a central role for altered ubiquitination. The smoking-induced gene expression profiles overlap significantly with profiles present in blood cells of patients with lung cancer or coronary heart disease, diseases strongly associated with tobacco smoking. These results provide proof-of-principle support to the suggestion that omic profiling in peripheral blood has the potential of identifying early, disease-related perturbations caused by toxic exposures and may be a useful tool in hazard and risk assessment.

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