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  • 201. Gonzalez, C. A.
    et al.
    Megraud, F.
    Buissonniere, A.
    Lujan Barroso, L.
    Agudo, A.
    Duell, E. J.
    Boutron-Ruault, M. C.
    Clavel-Chapelon, F.
    Palli, D.
    Krogh, V.
    Mattiello, A.
    Tumino, R.
    Sacerdote, C.
    Quiros, J. R.
    Sanchez-Cantalejo, E.
    Navarro, C.
    Barricarte, A.
    Dorronsoro, M.
    Khaw, K. -T
    Wareham, N.
    Allen, N. E.
    Tsilidis, K. K.
    Bueno-de-Mesquita, H. Bas
    Jeurnink, S. M.
    Numans, M. E.
    Peeters, P. H. M.
    Lagiou, P.
    Valanou, E.
    Trichopoulou, A.
    Kaaks, R.
    Lukanova-McGregor, A.
    Bergman, M. M.
    Boeing, H.
    Manjer, J.
    Lindkvist, B.
    Stenling, Roger
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Mortensen, L. M.
    Overvad, K.
    Olsen, A.
    Tjonneland, A.
    Bakken, K.
    Dumeaux, V.
    Lund, E.
    Jenab, M.
    Romieu, I.
    Michaud, D.
    Mouw, T.
    Carneiro, F.
    Fenge, C.
    Riboli, E.
    Helicobacter pylori infection assessed by ELISA and by immunoblot and noncardia gastric cancer risk in a prospective study: the Eurgast-EPIC project2012In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, no 5, p. 1320-1324Article in journal (Refereed)
    Abstract [en]

    In epidemiological studies, Helicobacter pylori infection is usually detected by enzyme-linked immunosorbent assay (ELISA). However, infection can spontaneously clear from the mucosa during the progression of atrophy and could lead to substantial under-detection of infection and underestimation of its effect on gastric cancer (GC) risk. Antibodies detected by western blot are known to persist longer after the loss of the infection. In a nested case-control study from the Eurogast-EPIC cohort, including 88 noncardia GC cases and 338 controls, we assessed the association between noncardia GC and H. pylori infection comparing antibodies detected by western blot (HELICOBLOT2.1) to those detected by ELISA (Pyloriset EIA-GIII((R))). By immunoblot, 82 cases (93.2%) were H. pylori positive, 10 of these cases (11.4%) were negative by ELISA and only 6 cases (6.8%) were negative by both ELISA and immunoblot. Multivariable odds ratio (OR) for noncardia GC comparing immunoglobulin G positive versus negative by ELISA was 6.8 [95% confidence interval (CI) 3.0-15.1], and by immunoblot, the OR was 21.4 (95% CI 7.1-64.4). Using a western blot assay, nearly all noncardia GC were classified as H. pylori positive and the OR was more than threefold higher than the OR assessed by ELISA, supporting the hypothesis that H. pylori infection is a necessary condition for noncardia GC.

  • 202. Gonzalez, Carlos A
    et al.
    Pera, Guillem
    Agudo, Antonio
    Bueno-de-Mesquita, H Bas
    Ceroti, Marco
    Boeing, Heiner
    Schulz, Mandy
    Del Giudice, Giuseppe
    Plebani, Mario
    Carneiro, Fátima
    Berrino, Franco
    Sacerdote, Carlotta
    Tumino, Rosario
    Panico, Salvatore
    Berglund, Göran
    Simane, Henrik
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Stenling, Roger
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Martinez, Carmen
    Dorronsoro, Miren
    Barricarte, Aurelio
    Navarro, Carmen
    Quiros, José R
    Allen, Naomi
    Key, Timothy J
    Bingham, Sheila
    Day, Nicholas E
    Linseisen, Jakob
    Nagel, Gabriele
    Overvad, Kim
    Jensen, Majken K
    Olsen, Anja
    Tjänneland, Anne
    Bächner, Frederike L
    Peeters, Petra H M
    Numans, Mattijs E
    Clavel-Chapelon, Francoise
    Boutron-Ruault, Marie-Christine
    Roukos, Dimitrios
    Trichopoulou, Antonia
    Psaltopoulou, Theodora
    Lund, Eiliv
    Casagrande, Corinne
    Slimani, Nadia
    Jenab, Mazda
    Riboli, Elio
    Fruit and vegetable intake and the risk of stomach and oesophagus adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST).2006In: International Journal of Cancer, ISSN 0020-7136, Vol. 118, no 10, p. 2559-66Article in journal (Refereed)
  • 203. González, Carlos A
    et al.
    Jakszyn, Paula
    Pera, Guillem
    Agudo, Antonio
    Bingham, Sheila
    Palli, Domenico
    Ferrari, Pietro
    Boeing, Heiner
    del Giudice, Giuseppe
    Plebani, Mario
    Carneiro, Fátima
    Nesi, Gabriella
    Berrino, Franco
    Sacerdote, Carlotta
    Tumino, Rosario
    Panico, Salvatore
    Berglund, Göran
    Simán, Henrik
    Nyrén, Olof
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Martinez, Carmen
    Dorronsoro, Miren
    Barricarte, Aurelio
    Navarro, Carmen
    Quirós, José R
    Allen, Naomi
    Key, Timothy J
    Day, Nicholas E
    Linseisen, Jakob
    Nagel, Gabriele
    Bergmann, Manuela M
    Overvad, Kim
    Jensen, Majken K
    Tjonneland, Anne
    Olsen, Anja
    Bueno-de-Mesquita, H Bas
    Ocke, Marga
    Peeters, Petra H M
    Numans, Mattijs E
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Trichopoulou, Antonia
    Psaltopoulou, Theodora
    Roukos, Dimitrios
    Lund, Eiliv
    Hemon, Bertrand
    Kaaks, Rudolf
    Norat, Teresa
    Riboli, Elio
    Meat intake and risk of stomach and esophageal adenocarcinoma within the European Prospective Investigation Into Cancer and Nutrition (EPIC).2006In: Journal of National Cancer Institute, ISSN 1460-2105, Vol. 98, no 5, p. 345-54Article in journal (Refereed)
  • 204. González, Carlos A
    et al.
    Travier, Noemie
    Luján-Barroso, Leila
    Castellsagué, Xavier
    Bosch, F Xavier
    Roura, Esther
    Bueno-de-Mesquita, H Bas
    Palli, Domenico
    Boeing, Heiner
    Pala, Valeria
    Sacerdote, Carlotta
    Tumino, Rosario
    Panico, Salvatore
    Manjer, Jonas
    Dillner, Joakim
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Kjellberg, Lennart
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Sanchez, María-José
    Altzibar, Jone M
    Barricarte, Aurelio
    Navarro, Carmen
    Rodriguez, Laudina
    Allen, Naomi
    Key, Timothy J
    Kaaks, Rudolf
    Rohrmann, Sabine
    Overvad, Kim
    Olsen, Anja
    Tjønneland, Anne
    Munk, Christian
    Kjaer, Susanne Krüger
    Peeters, Petra H M
    van Duijnhoven, Fränzel J B
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Trichopoulou, Antonia
    Benetou, Vasiliki
    Naska, Androniki
    Lund, Eiliv
    Engeset, Dagrun
    Skeie, Guri
    Franceschi, Silvia
    Slimani, Nadia
    Rinaldi, Sabina
    Riboli, Elio
    Dietary factors and in situ and invasive cervical cancer risk in the European prospective investigation into cancer and nutrition study.2011In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 129, no 2, p. 449-459Article in journal (Refereed)
    Abstract [en]

    Some dietary factors could be involved as cofactors in cervical carcinogenesis, but evidence is inconclusive. There are no data about the effect of fruits and vegetables intake (F&V) on cervical cancer from cohort studies. We examined the association between the intake of F&V and selected nutrients and the incidence of carcinoma in situ (CIS) and invasive squamous cervical cancer (ISC) in a prospective study of 299,649 women, participating in the European Prospective Investigation into Cancer and Nutrition study. Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CI). A calibration study was used to control measurement errors in the dietary questionnaire. After a mean of 9 years of follow-up, 253 ISC and 817 CIS cases were diagnosed. In the calibrated model, we observed a statistically significant inverse association of ISC with a daily increase in intake of 100 g of total fruits (HR 0.83; 95% CI 0.72-0.98) and a statistically nonsignificant inverse association with a daily increase in intake of 100 g of total vegetables (HR 0.85: 95% CI 0.65-1.10). Statistically nonsignificant inverse associations were also observed for leafy vegetables, root vegetables, garlic and onions, citrus fruits, vitamin C, vitamin E and retinol for ISC. No association was found regarding beta-carotene, vitamin D and folic acid for ISC. None of the dietary factors examined was associated with CIS. Our study suggests a possible protective role of fruit intake and other dietary factors on ISC that need to be confirmed on a larger number of ISC cases.

  • 205. Gormally, Emmanuelle
    et al.
    Hainaut, Pierre
    Caboux, Elodie
    Airoldi, Luisa
    Autrup, Herman
    Malaveille, Christian
    Dunning, Alison
    Garte, Seymour
    Matullo, Giuseppe
    Overvad, Kim
    Tjonneland, Anne
    Clavel-Chapelon, Francoise
    Boffetta, Paolo
    Boeing, Heiner
    Trichopoulou, Antonia
    Palli, Domenico
    Krogh, Vittorio
    Tumino, Rosario
    Panico, Salvatore
    Bueno-de-Mesquita, H Bas
    Peeters, Petra H
    Lund, Eiliv
    Gonzalez, Carlos A
    Martinez, Carmen
    Dorronsoro, Miren
    Barricarte, Aurelio
    Tormo, M Jose
    Quiros, J Ramón
    Berglund, Goran
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Day, Nicholas E
    Key, Timothy J
    Veglia, Fabrizio
    Peluso, Marco
    Norat, Teresa
    Saracci, Rodolfo
    Kaaks, Rudolf
    Riboli, Elio
    Vineis, Paolo
    Amount of DNA in plasma and cancer risk: a prospective study.2004In: International Journal of Cancer, ISSN 0020-7136, Vol. 111, no 5, p. 746-9Article in journal (Refereed)
  • 206. Gormally, Emmanuelle
    et al.
    Vineis, Paolo
    Matullo, Giuseppe
    Veglia, Fabrizio
    Caboux, Elodie
    Le Roux, Emilie
    Peluso, Marco
    Garte, Seymour
    Guarrera, Simonetta
    Munnia, Armelle
    Airoldi, Luisa
    Autrup, Herman
    Malaveille, Christian
    Dunning, Alison
    Overvad, Kim
    Tjønneland, Anne
    Lund, Eiliv
    Clavel-Chapelon, Françoise
    Boeing, Heiner
    Trichopoulou, Antonia
    Palli, Domenico
    Krogh, Vittorio
    Tumino, Rosario
    Panico, Salvatore
    Bueno-de-Mesquita, H Bas
    Peeters, Petra H
    Pera, Guillem
    Martinez, Carmen
    Dorronsoro, Miren
    Barricarte, Aurelio
    Navarro, Carmen
    Quirós, José Ramón
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Day, Nicholas E
    Key, Timothy J
    Saracci, Rodolfo
    Kaaks, Rudolf
    Riboli, Elio
    Hainaut, Pierre
    TP53 and KRAS2 mutations in plasma DNA of healthy subjects and subsequent cancer occurrence: a prospective study.2006In: Cancer Research, ISSN 0008-5472, Vol. 66, no 13, p. 6871-6Article in journal (Refereed)
  • 207.
    Gotthold, David
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Vegetable omega-3 and omega-6 fatty acids and risk of myocardial infarction2018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 208. Grote, VA
    et al.
    Kaaks, R
    Nieters, A
    Tjonneland, A
    Halkjaer, J
    Overvad, K
    Nielsen, MR Skjelbo
    Boutron-Ruault, MC
    Clavel-Chapelon, F
    Racine, A
    Teucher, B
    Becker, S
    Pischon, T
    Boeing, H
    Trichopoulou, A
    Cassapa, C
    Stratigakou, V
    Palli, D
    Krogh, V
    Tumino, R
    Vineis, P
    Panico, S
    Rodriguez, L
    Duell, EJ
    Sanchez, M-J
    Dorronsoro, M
    Navarro, C
    Gurrea, AB
    Siersema, PD
    Peeters, PHM
    Ye, W
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lindkvist, B
    Johansen, D
    Khaw, K-T
    Wareham, N
    Allen, NE
    Travis, RC
    Fedirko, V
    Jenab, M
    Michaud, DS
    Chuang, S-C
    Romaguera, D
    Bueno-de-Mesquita, HB
    Rohrmann, S
    Inflammation marker and risk of pancreatic cancer: a nested case-control study within the EPIC cohort2012In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 106, no 11, p. 1866-1874Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Established risk factors for pancreatic cancer include smoking, long-standing diabetes, high body fatness, and chronic pancreatitis, all of which can be characterised by aspects of inflammatory processes. However, prospective studies investigating the relation between inflammatory markers and pancreatic cancer risk are scarce.

    METHODS: We conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, measuring prediagnostic blood levels of C-reactive protein (CRP), interleukin-6 (IL-6), and soluble receptors of tumour necrosis factor-a (sTNF-R1, R2) in 455 pancreatic cancer cases and 455 matched controls. Odds ratios (ORs) were estimated using conditional logistic regression models.

    RESULTS: None of the inflammatory markers were significantly associated with risk of pancreatic cancer overall, although a borderline significant association was observed for higher circulating sTNF-R2 (crude OR = 1.52 (95% confidence interval (CI) 0.97-2.39), highest vs lowest quartile). In women, however, higher sTNF-R1 levels were significantly associated with risk of pancreatic cancer (crude OR = 1.97 (95% CI 1.02-3.79)). For sTNF-R2, risk associations seemed to be stronger for diabetic individuals and those with a higher BMI.

    CONCLUSION: Prospectively, CRP and IL-6 do not seem to have a role in our study with respect to risk of pancreatic cancer, whereas sTNF-R1 seemed to be a risk factor in women and sTNF-R2 might be a mediator in the risk relationship between overweight and diabetes with pancreatic cancer. Further large prospective studies are needed to clarify the role of proinflammatory proteins and cytokines in the pathogenesis of exocrine pancreatic cancer. British Journal of Cancer (2012) 106, 1866-1874. doi:10.1038/bjc.2012.172 www.bjcancer.com Published online 26 April 2012 (C) 2012 Cancer Research UK

  • 209. Grönlund, Hans
    et al.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wikström, Max
    de Faire, Ulf
    Frostegård, Johan
    Low levels of IgM antibodies against phosphorylcholine predict development of acute myocardial infarction in a population-based cohort from northern Sweden.2009In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 16, no 3, p. 382-386Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Phosphorylcholine (PC) is one important epitope on oxidized low-density lipoprotein that may play an important role by contributing to the atherogenicity of oxidized low-density lipoprotein. IgM antibodies against PC (anti-PC) are present ubiquitously in the population as natural antibodies. We here determine the association between anti-PC and incidence of myocardial infarction (MI). METHODS: We studied 462 incident cases of first events of MI and 888 age-matched and sex-matched controls identified through 13 years of follow-up (1987-1999) of participants in a population-based study from northern Sweden. Relative risks (RRs) with 95% confidence intervals (CIs) of incident MI with adjustments for age, sex, geographical region, hypertension, diabetes, BMI, smoking habits, s-cholesterol and high-sensitivity C-reactive protein were determined. Anti-PC levels were measured by enzyme-linked immunoassay. RESULTS: Low anti-PC values were associated with increased risk of MI. Significant associations were found for values below 26.8 U/ml, corresponding to the lowest 25th percentile, and the highest association was seen below 16.9 U/ml. These results remained almost the same after adjustment for confounding factors (RR crude: 1.56, CI: 1.07-2.28 and RR adjusted: 1.69, CI: 1.09-2.54). CONCLUSION: Low levels of natural IgM anti-PC could play an important role as risk markers for development of MI. Adjustment for common confounders only marginally affected the RR, suggesting that the addition of IgM anti-PC add independent information to the more traditional risk factors.

  • 210. Grøntved, Anders
    et al.
    Koivula, Robert W
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Østergaard, Lars
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Skåne University Hospital Malmö, Malmö, Sweden.
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Skåne University Hospital Malmö, Malmö, Sweden.
    Bicycling to Work and Primordial Prevention of Cardiovascular Risk: A Cohort Study Among Swedish Men and Women2016In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 5, no 11, article id e004413Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Bicycling to work may be a viable approach for achieving physical activity that provides cardiovascular health benefits. In this study we investigated the relationship of bicycling to work with incidence of obesity, hypertension, hypertriglyceridemia, and impaired glucose tolerance across a decade of follow-up in middle-aged men and women.

    METHODS AND RESULTS: We followed 23 732 Swedish men and women with a mean age of 43.5 years at baseline who attended a health examination twice during a 10-year period (1990-2011). In multivariable adjusted models we calculated the odds of incident obesity, hypertension, hypertriglyceridemia, and impaired glucose tolerance, comparing individuals who commuted to work by bicycle with those who used passive modes of transportation. We also examined the relationship of change in commuting mode with incidence of these clinical risk factors. Cycling to work at baseline was associated with lower odds of incident obesity (odds ratio [OR]=0.85, 95% CI 0.73-0.99), hypertension (OR=0.87, 95% CI 0.79-0.95), hypertriglyceridemia (OR=0.85, 95% CI 0.76-0.94), and impaired glucose tolerance (OR=0.88, 95% CI 0.80-0.96) compared with passive travel after adjusting for putative confounding factors. Participants who maintained or began bicycling to work during follow-up had lower odds of obesity (OR=0.61, 95% CI 0.50-0.73), hypertension (OR=0.89, 95% CI 0.80-0.98), hypertriglyceridemia (OR=0.80, 95% CI 0.70-0.90), and impaired glucose tolerance (OR=0.82, 95% CI 0.74-0.91) compared with participants not cycling to work at both times points or who switched from cycling to other modes of transport during follow-up.

    CONCLUSIONS: These data suggest that commuting by bicycle to work is an important strategy for primordial prevention of clinical cardiovascular risk factors among middle-aged men and women.

  • 211. Gunter, Marc J.
    et al.
    Murphy, Neil
    Cross, Amanda J..
    Dossus, Laure
    Dartois, Laureen
    Fagherazzi, Guy
    Kaaks, Rudolf
    Kühn, Tilman
    Boeing, Heiner
    Aleksandrova, Krasimira
    Tjønneland, Anne
    Olsen, Anja
    Overvad, Kim
    Larsen, Sofus Christian
    Redondo Cornejo, Maria Luisa
    Agudo, Antonio
    Sánchez Pérez, María José
    Altzibar, Jone M.
    Navarro, Carmen
    Ardanaz, Eva
    Khaw, Kay-Tee
    Butterworth, Adam
    Bradbury, Kathryn E.
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Palli, Domenico
    Grioni, Sara
    Vineis, Paolo
    Panico, Salvatore
    Tumino, Rosario
    Bueno-de-Mesquita, Bas
    Siersema, Peter
    Leenders, Max
    Beulens, Joline W. J.
    Uiterwaal, Cuno U.
    Wallström, Peter
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Landberg, Rikard
    Weiderpass, Elisabete
    Skeie, Guri
    Braaten, Tonje
    Brennan, Paul
    Licaj, Idlir
    Muller, David C.
    Sinha, Rashmi
    Wareham, Nick
    Riboli, Elio
    Coffee Drinking and Mortality in 10 European Countries: A Multinational Cohort Study2017In: Annals of Internal Medicine, ISSN 0003-4819, E-ISSN 1539-3704, Vol. 167, no 4, p. 236-247Article in journal (Refereed)
    Abstract [en]

    Background: The relationship between coffee consumption and mortality in diverse European populations with variable coffee preparation methods is unclear.

    Objective: To examine whether coffee consumption is associated with all-cause and cause-specific mortality.

    Design: Prospective cohort study.

    Setting: 10 European countries.

    Participants: 521 330 persons enrolled in EPIC (European Prospective Investigation into Cancer and Nutrition).

    Measurements: Hazard ratios (HRs) and 95% CIs estimated using multivariable Cox proportional hazards models. The association of coffee consumption with serum biomarkers of liver function, inflammation, and metabolic health was evaluated in the EPIC Biomarkers subcohort (n = 14 800).

    Results: During a mean follow-up of 16.4 years, 41 693 deaths occurred. Compared with nonconsumers, participants in the highest quartile of coffee consumption had statistically significantly lower all-cause mortality (men: HR, 0.88 [95% CI, 0.82 to 0.95]; P for trend < 0.001; women: HR, 0.93 [CI, 0.87 to 0.98]; P for trend = 0.009). Inverse associations were also observed for digestive disease mortality for men (HR, 0.41 [CI, 0.32 to 0.54]; P for trend < 0.001) and women (HR, 0.60 [CI, 0.46 to 0.78]; P for trend < 0.001). Among women, there was a statistically significant inverse association of coffee drinking with circulatory disease mortality (HR, 0.78 [CI, 0.68 to 0.90]; P for trend < 0.001) and cerebrovascular disease mortality (HR, 0.70 [CI, 0.55 to 0.90]; P for trend = 0.002) and a positive association with ovarian cancer mortality (HR, 1.31 [CI, 1.07 to 1.61]; P for trend = 0.015). In the EPIC Biomarkers subcohort, higher coffee consumption was associated with lower serum alkaline phosphatase; alanine aminotransferase; aspartate aminotransferase; γ-glutamyltransferase; and, in women, C-reactive protein, lipoprotein(a), and glycated hemoglobin levels.

    Limitations: Reverse causality may have biased the findings; however, results did not differ after exclusion of participants who died within 8 years of baseline. Coffee-drinking habits were assessed only once.

    Conclusion: Coffee drinking was associated with reduced risk for death from various causes. This relationship did not vary by country.

    Primary Funding Source: European Commission Directorate-General for Health and Consumers and International Agency for Research on Cancer.

  • 212.
    Gylling, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Myte, Robin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ulvik, Arve
    Bevital AS, Laboratory building, Bergen, Norway.
    Ueland, Per Magne
    Department of Clinical Science, University of Bergen and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway.
    Midttun, Øivind
    Bevital AS, Laboratory building, Bergen, Norway.
    Schneede, Jørn
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Häggström, Jenny
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    One-carbon metabolite ratios as functional B-vitamin markers and in relation to colorectal cancer risk2019In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, no 5, p. 68p. 947-956Article in journal (Other academic)
    Abstract [en]

    Background: One-carbon metabolism biomarker are easily measured in plasma, but analyzing them one at a time in relation to disease does not take into account the interdependence of the many factors involved. The relative dynamics of major one-carbon metabolism branches can be assessed by relating the functional B-vitamin marker total homocysteine (tHcy) to transsulfuration (total cysteine) and methylation (creatinine) outputs.

    Objective: We validated the ratios of tHcy to total cysteine (Hcy:Cys), tHcy to creatinine (Hcy:Cre), and tHcy to cysteine to creatinine (Hcy:Cys:Cre) as functional markers of B-vitamin status. We also calculated the associations of these ratios to colorectal cancer (CRC) risk.

    Design: The relative contribution of potential confounders to the variance of the ratio-based B-vitamin markers was calculated by linear regression in a nested case-control study of 613 CRC cases and 1211 matched controls. Total B-vitamin status was represented by a summary score comprising Z-standardized plasma concentrations of folate, cobalamin, betaine, pyridoxal 5´-phosphate, and riboflavin. Associations with CRC risk were estimated using conditional logistic regression.

    Results: The ratio-based B-vitamin markers all outperformed tHcy as markers of total B-vitamin status, in both CRC cases and controls. Associations with CRC risk were similar for the ratio-based B-vitamin markers and total B-vitamin status (approximately 25% lower risk for high versus low B-vitamin status).

    Conclusions: Ratio-based B-vitamin markers were good predictors of total B-vitamin status, and displayed similar associations with CRC risk. Since tHcy and creatinine are routinely clinically analyzed, Hcy:Cre could be easily implemented in clinical practice to aid interpretation of tHcy results.

  • 213.
    Gylling, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Schneede, Jörn
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Ueland, Per Magne
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Low folate levels are associated with reduced risk of colorectal cancer in a population with low folate status2014In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 23, no 10, p. 2136-2144Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A diet rich in folate is associated with a reduced colorectal cancer risk, whereas the role of circulating levels is less clear. The aim of this study was to relate prediagnostic plasma folate, vitamin B12, and homocysteine concentrations to the risk of colorectal cancer.

    METHODS: This was a prospective case-control study of 331 cases and 662 matched controls nested within the population-based Northern Sweden Health and Disease Study. Median follow-up time from recruitment to diagnosis was 10.8 years.

    RESULTS: Plasma folate concentrations were positively related to colorectal cancer risk; multivariate odds ratios were 1.62 [95% confidence intervals (CI), 1.08-2.42] and 1.42 (95% CI, 0.94-2.21) for the middle and highest versus lowest tertile, respectively. In subjects with follow-up <10.8 years, a statistically significant doubled risk was observed for the middle and highest versus lowest tertile, whereas findings for longer follow-up times were null. A positive risk relationship was also observed for tumor stage III-IV but not I-II. Plasma vitamin B12 concentrations were inversely associated with rectal cancer risk. Homocysteine was not significantly related to colorectal cancer risk.

    CONCLUSIONS: In this population-based, nested case-control study, low plasma folate concentrations were associated with a reduced colorectal cancer risk. This protective role was mainly observed in subjects with higher tumor stage or shorter follow-up time between recruitment and diagnosis. Low circulating folate status may protect against colorectal cancer or suppress progression of preneoplastic or neoplastic lesions.

    IMPACT: These findings may have relevance for the ongoing debate about mandatory folic acid fortification of flour.

  • 214. Göhler, S.
    et al.
    Da Silva Filho, M. I.
    Johansson, R.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Enquist-Olsson, K.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Henriksson, R.
    Hemminki, K.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Försti, A.
    Functional germline variants in driver genes of breast cancer2014In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 50, p. S233-S233Article in journal (Other academic)
  • 215. Göhler, Stella
    et al.
    Da Silva Filho, Miguel Inacio
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Enquist-Olsson, Kerstin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Cancer Center Stockholm Gotland, 10239 Stockholm, Sweden.
    Hemminki, Kari
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Försti, Asta
    Functional germline variants in driver genes of breast cancer2017In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 28, no 4, p. 259-271Article in journal (Refereed)
    Abstract [en]

    Purpose Germline mutations in tumour suppressor genes cause various cancers. These genes are also somatically mutated in sporadic tumours. We hypothesized that there may also be cancer-related germline variants in the genes commonly mutated in sporadic breast tumours. Methods After excluding the well-characterized breast cancer (BC) genes, we screened 15 novel genes consistently classified as BC driver genes in next-generation sequencing approaches for single nucleotide polymorphisms (SNPs). Altogether 40 SNPs located in the core promoter, 5'- and 3'-UTR or which were nonsynonymous SNPs were genotyped in 782 Swedish incident BC cases and 1,559 matched controls. After statistical analyses, further evaluations related to functional prediction and signatures of selection were performed. Results TBX3 was associated with BC risk (rs2242442: OR = 0.76, 95% CI 0.64-0.92, dominant model) and with less aggressive tumour characteristics. An association with BC survival and aggressive tumour characteristics was detected for the genes ATR (rs2227928: HR = 1.63; 95% CI 1.00-2.64, dominant model), RUNX1 (rs17227210: HR = 3.50, 95% CI 1.42-8.61, recessive model) and TTN (rs2303838: HR = 2.36; 95% CI 1.04-5.39; rs2042996: HR = 2.28; 95% CI 1.19-4.37, recessive model). According to the experimental ENCODE data all these SNPs themselves or SNPs in high linkage disequilibrium with them (r (2) ae<yen> 0.80) were located in regulatory regions. RUNX1 and TTN showed also several signatures of positive selection. Conclusion The study gave evidence that germline variants in BC driver genes may have impact on BC risk and/or survival. Future studies could discover further germline variants in known or so far unknown driver genes which contribute to cancer development.

  • 216. Halkjaer, J
    et al.
    Olsen, A
    Bjerregaard, L J
    Deharveng, G
    Tjønneland, A
    Welch, A A
    Crowe, F L
    Wirfält, E
    Hellström, Veronica
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Niravong, M
    Touvier, M
    Linseisen, J
    Steffen, A
    Ocké, M C
    Peeters, P H M
    Chirlaque, M D
    Larrañaga, N
    Ferrari, P
    Contiero, P
    Frasca, G
    Engeset, D
    Lund, E
    Misirli, G
    Kosti, M
    Riboli, E
    Slimani, N
    Bingham, S
    Intake of total, animal and plant proteins, and their food sources in 10 countries in the European prospective investigation into cancer and nutrition2009In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 63 Suppl 4, p. S16-36Article in journal (Refereed)
    Abstract [en]

    This study shows that intake of protein, especially of animal origin, differs across the 10 European countries, and also shows some differences in food sources of protein across Europe.

  • 217.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    No, no mass folic acid supplementation in Sweden--not yet anyway. Incidence of cancer and cardiovascular diseases can increase and probable DNA changes are unsettling2007In: Lakartidningen, ISSN 0023-7205, Vol. 104, no 38, p. 2670-2; discussion 2673Article in journal (Refereed)
  • 218.
    Hallmans, Göran
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Agren, A
    Johansson, G
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology, Periodontology.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, JH
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindahl, B
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Nilsson, M
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Cardiovascular disease and diabetes in the Northern Sweden Health and Disease Study Cohort: evaluation of risk factors and their interactions.2003In: Scandinavian Journal of Public Health. Supplement Links, ISSN 1403-4956, Vol. 61, p. 18-24Article in journal (Refereed)
    Abstract [en]

    The purpose of this paper is, first, to describe the organization, sampling procedures, availability of samples/database, ethical considerations, and quality control program of the Northern Sweden Health and Disease Study Cohort. Secondly, some examples are given of studies on cardiovascular disease and diabetes with a focus on the biomarker programme. The cohort has been positioned as a national and international resource for scientific research.

  • 219.
    Hallmans, Göran
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Vaught, Jimmie B
    Best practices for establishing a biobank2011In: Methods in Molecular Biology, ISSN 1064-3745, E-ISSN 1940-6029, Vol. 675, p. 241-260Article in journal (Refereed)
    Abstract [en]

    A biobank may be defined as the long-term storage of biological samples for research or clinical purposes. In addition to storage facilities, a biobank may comprise a complete organization with biological samples, data, personnel, policies, and procedures for handling specimens and performing other services, such as the management of the database and the planning of scientific studies. This combination of facilities, policies, and processes may also be called a biological resource center (BRC) ( www.iarc.fr ). Research using specimens from biobanks is regulated by European Union (EU) recommendations (Recommendations on Research on Human Biological Materials. The draft recommendation on research on human biological materials was approved by CDBI at its plenary meeting on 20 October 2005) and by voluntary best practices from the U.S. National Cancer Institute (NCI) ( http://biospecimens.cancer.gov ) and other organizations. Best practices for the management of research biobanks vary according to the institution and differing international regulations and standards. However, there are many areas of agreement that have resulted in best practices that should be followed in order to establish a biobank for the custodianship of high-quality specimens and data.

  • 220.
    Hallmans, Göran
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Nutritional Research.
    Zhang, Jie-Xian
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Nutritional Research.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Stattin, P
    Johansson, Anders
    Umeå University, Faculty of Medicine, Odontology, Periodontology.
    Johansson, I
    Hultén, K
    Winkvist, A
    Aman, P
    Lenner, P
    Adlercreutz, H
    Rye, lignans and human health2003In: Proceedings of the Nutrition Society, ISSN 0029-6651, E-ISSN 1475-2719, Vol. 62, no 1, p. 193-9Article in journal (Refereed)
    Abstract [en]

    Rye bran contains a high content not only of dietary fibre, but also of plant lignans and other bioactive compounds in the so-called dietary fibre complex. Blood concentrations of lignans such as enterolactone have been used as biomarkers of intake of lignan-rich plant food. At present,evidence from studies in human subjects does not warrant the conclusion that rye, whole grains orphyto-oestrogens protect against cancer. Some studies, however, have pointed in that direction,especially in relation to cancers of the upper digestive tract. A number of prospective epidemiological studies have clearly shown a protective effect of wholegrain cereals against myocardial infarctions. A corresponding protective effect against diabetes and ischaemic stroke(brain infarct) has also been demonstrated. It seems reasonable to assume that these protective effects are associated with one or more factors in the dietary fibre complex.

  • 221. Hampe, C S
    et al.
    Hall, T R
    Ågren, Åsa
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Nutritional Research.
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Family Medicine. Allmänmedicin.
    Longitudinal changes in epitope recognition of autoantibodies against glutamate decarboxylase 65 (GAD65Ab) in prediabetic adults developing diabetes.2007In: Clin Exp Immunol, ISSN 0009-9104, Vol. 148, no 1, p. 72-8Article in journal (Refereed)
  • 222. Handberg, A
    et al.
    Norberg, Margareta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Hallmans, G
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Attermann, J
    Eriksson, J W
    Soluble CD36 (sCD36) Clusters with Markers of Insulin Resistance, and High sCD36 Is Associated with Increased Type 2 Diabetes Risk.2010In: The Journal of clinical endocrinology and metabolism, ISSN 1945-7197Article in journal (Refereed)
    Abstract [en]

    Context and Objective: Soluble CD36 (sCD36) may be an early marker of insulin resistance and atherosclerosis. The objective of this prospective study was to evaluate sCD36 as a predictor of type 2 diabetes and to study its relationship with components of the metabolic syndrome (MetSy). Design, Setting, Participants, and Outcome Measures: We conducted a case-referent study nested within a population-based health survey. Baseline variables included sCD36, body mass index, blood pressure, blood lipids, adipokines, inflammatory markers, and beta-cell function. A total of 173 initially nondiabetic cohort members who developed type 2 diabetes during 10 yr of follow-up were matched (1:2) with referents. Exploratory factor analysis was applied to hypothesize affiliation of sCD36 to the MetSy components. Results: Doubling of baseline sCD36 increases the odds ratio for diabetes development by 1.24 in the general study population and by 1.45 in the female population (P < 0.025). Comparing upper sCD36 quartiles with lower, odds ratio for diabetes was 4.6 in women (P = 0.001), 3.15 in men (P = 0.011), and 2.6 in obese individuals (P < 0.025). Multivariate analysis shows that sCD36 does not predict diabetes independent of fasting plasma glucose and insulin. Factor analysis of 15 variables generates a six-factor model explaining 66-69% of total variance, where sCD36, body mass index, insulin, proinsulin, and leptin were assigned to the obesity/insulin resistance cluster. Conclusions: Upper quartile sCD36 is associated with elevated diabetes risk independent of age, gender, and obesity. Baseline sCD36 does not, however, predict diabetes independent of fasting glucose and insulin. sCD36 clusters with important markers of insulin resistance and MetSy that are key predictors of type 2 diabetes.

  • 223. Hansen, RD
    et al.
    Larsen, R
    Borre, M
    Friis, S
    Åman, P
    Steingrimsdottir, L
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Overgaard, K
    Tjonneland, A
    Nordic lifestyle intervention trial on prostate cancer progression (NILS)2012In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 48, no S5, p. S286-S286Article in journal (Other academic)
  • 224. Hansson, Ida
    et al.
    Lynch, Kristian F
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lernmark, Åke
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    High-titer GAD65 autoantibodies detected in adult diabetes patients using a high efficiency expression vector and cold GAD65 displacement.2011In: Autoimmunity, ISSN 0891-6934, E-ISSN 1607-842X, Vol. 44, no 2, p. 129-136Article in journal (Refereed)
    Abstract [en]

    Adult type 2 diabetes patients with GAD65 autoantibodies (GADA) are known as latent autoimmune diabetes in adults (LADA). It has been suggested that GADA in LADA patients preferentially bind to the N-terminal end of GAD65. Using the N-terminal end extension of ³⁵S-GAD65 generated by the pEx9 plasmid, we tested the hypothesis that GADA in LADA patients preferentially react with ³⁵S-GAD65 from the pEx9 plasmid compared to the normal length pThGAD65 plasmid. Healthy control subjects (n = 250) were compared with type 1 (n = 23), type 2 (n = 290), and unspecified (n = 57) diabetes patients. In addition, radio-binding assays for GADA with ³⁵S-GAD65 generated from both the pEx9 and pThGAD65 plasmids were used in displacement assays with an excess of recombinant human GAD65 (2 μg/mL) to correct for non-specific binding. ³⁵S-GAD65 produced by either pEx9 or pThGAD65 did not differ in binding among the healthy controls and among the type 1 diabetes patients. Among the type 2 and unspecified patients, there were 4/290 and 3/57 patients, respectively, with binding to the pEx9 but not to the pThGAD65 generated ³⁵S-GAD65. In the displacement assay, we discovered 14 patients with very high-titer GADA among the type 1 (n = 3, 12,272-29,915 U/mL), type 2 (n = 7; 12,398-334,288 U/mL), and unspecified (n = 4; 20,773-4,053,580 U/mL) patients. All samples were fully displaced following appropriate dilution. We conclude that pThGAD65 is preferred for the coupled in vitro transcription translation of ³⁵S-GAD65 and that displacement with recombinant GAD65 may detect very high-titer GADA with possible clinical relevance.

  • 225. Hart, Andrew R
    et al.
    Luben, Robert
    Olsen, Anja
    Tjonneland, Anne
    Linseisen, Jakob
    Nagel, Gabriele
    Berglund, Goran
    Lindgren, Stefan
    Grip, Olof
    Key, Timothy
    Appleby, Paul
    Bergmann, Manuela M
    Boeing, Heiner
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Danielsson, Ake
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Sjodin, Hubert
    Hagglund, Gun
    Overvad, Kim
    Palli, Domenico
    Masala, Giovanna
    Riboli, Elio
    Kennedy, Hugh
    Welch, Ailsa
    Khaw, Kay-Tee
    Day, Nicholas
    Bingham, Sheila
    Diet in the Aetiology of Ulcerative Colitis: A European Prospective Cohort Study.2008In: Digestion, ISSN 1421-9867, Vol. 77, no 1, p. 57-64Article in journal (Refereed)
  • 226. Hebels, Dennie G. A. J.
    et al.
    Georgiadis, Panagiotis
    Keun, Hector C.
    Athersuch, Toby J.
    Vineis, Paolo
    Vermeulen, Roel
    Portengen, Lützen
    Bergdahl, Ingvar A.
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Palli, Domenico
    Bendinelli, Benedetta
    Krogh, Vittorio
    Tumino, Rosario
    Sacerdote, Carlotta
    Panico, Salvatore
    Kleinjans, Jos C. S.
    de Kok, Theo M. C. M.
    Smith, Martyn T.
    Kyrtopoulos, Soterios A.
    Performance in omics analyses of blood samples in long-term storage: opportunities for the exploitation of existing biobanks in environmental health research2013In: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 121, no 4, p. 480-487Article in journal (Refereed)
    Abstract [en]

    Background: The suitability for omic analysis of biosamples collected in previous decades and currently stored in biobanks is unknown.

    Objectives: We evaluated the influence of handling and storage conditions of blood-derived biosamples on transcriptomic, epigenomic (CpG methylation), plasma metabolomic [UPLC-ToFMS (ultra performance liquid chromatography-time-of-flight mass spectrometry)], and wide-target proteomic profiles.

    Methods: We collected fresh blood samples without RNA preservative in heparin, EDTA, or citrate and held them at room temperature for ≤ 24 hr before fractionating them into buffy coat, erythrocytes, and plasma and freezing the fractions at -80oC or in liquid nitrogen. We developed methodology for isolating RNA from the buffy coats and conducted omic analyses. Finally, we analyzed analogous samples from the EPIC-Italy and Northern Sweden Health and Disease Study biobanks.

    Results: Microarray-quality RNA could be isolated from buffy coats (including most biobank samples) that had been frozen within 8 hr of blood collection by thawing the samples in RNA preservative. Different anticoagulants influenced the metabolomic, proteomic, and to a lesser extent transcriptomic profiles. Transcriptomic profiles were most affected by the delay (as little as 2 hr) before blood fractionation, whereas storage temperature had minimal impact. Effects on metabolomic and proteomic profiles were noted in samples processed ≥ 8 hr after collection, but no effects were due to storage temperature. None of the variables examined significantly influenced the epigenomic profiles. No systematic influence of time-in-storage was observed in samples stored over a period of 13-17 years.

    Conclusions: Most samples currently stored in biobanks are amenable to meaningful omics analysis, provided that they satisfy collection and storage criteria defined in this study.

  • 227. Hemminki, Kari
    et al.
    Chen, Bowang
    Melander, Olle
    Manjer, Jonas
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hemminki, Akseli
    Smoking and body mass index as risk factors for subtypes of cancer of unknown primary2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 136, no 1, p. 246-247Article in journal (Refereed)
  • 228. Hermann, Silke
    et al.
    Rohrmann, Sabine
    Linseisen, Jakob
    Nieters, Alexandra
    Khan, Aneire
    Gallo, Valentina
    Overvad, Kim
    Tjønneland, Anne
    Raaschou-Nielsen, Ole
    Bergmann, Manuela
    Boeing, Heiner
    Becker, Nikolaus
    Kaaks, Rudolf
    Bas Bueno-de-Mesquita, H
    May, Anne
    Vermeulen, Roel
    Bingham, Sheila
    Khaw, Kay-Tee
    Key, Timothy
    Travis, Ruth
    Trichopoulou, Antonia
    Georgila, Christina
    Triantafylou, Dimitra
    Celentano, Egidio
    Krogh, Vittorio
    Masala, Giovanna
    Tumino, Rosario
    Agudo, Antonio
    Altzibar, Jone
    Ardanaz, Eva
    Martínez-García, Carmen
    Suárez, Marcial
    Tormo, Maria
    Braaten, Tonje
    Lund, Eiliv
    Manjer, Jonas
    Zackrisson, Sophia
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Malmer, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Boffetta, Paolo
    Brennan, Paul
    Slimani, Nadia
    Vineis, Paolo
    Riboli, Elio
    Level of education and the risk of lymphoma in the European prospective investigation into cancer and nutrition2010In: Journal of cancer research and clinical oncology, ISSN 1432-1335, Vol. 136, p. 71-77Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Lymphomas belong to the few cancer sites with increasing incidence over past decades, and only a few risk factors have been established. We explored the association between education and the incidence of lymphoma in the prospective EPIC study. MATERIALS AND METHODS: Within 3,567,410 person-years of follow-up, 1,319 lymphoma cases [1,253 non-Hodgkin lymphomas (NHL) and 66 Hodgkin lymphomas (HL)] were identified. Cox proportional hazard regression was used to examine the association between highest educational level (primary school or less, technical/professional school, secondary school, university) and lymphoma risk. RESULTS: Overall, no consistent associations between educational level and lymphoma risk were observed; however, associations were found for sub-groups of the cohort. We observed a higher risk of B-NHL (HR = 1.31, 95% CI = 1.02-1.68; n = 583) in women with the highest education level (university) but not in men. Concerning sub-classes of B-NHL, a positive association between education and risk of B cell chronic lymphatic leukaemia (BCLL) was observed only in women. In both genders, the risk of diffuse large B cell lymphoma (DLBCL) was significantly lower for subjects with university degree (HR = 0.46, 95% CI = 0.27-0.79) versus lowest educational level. No association was found for HL. CONCLUSION: We could not confirm an overall consistent association of education and risk of HL or NHL in this large prospective study; although, education was positively related to the incidence of BCLL and B-NHL (in women) but inversely to incidence of DLBCL. Due to limited number of cases in sub-classes and the large number of comparisons, the possibility of chance findings can not be excluded.

  • 229.
    Hoeft, Birgit
    et al.
    German Cancer Research Center, Heidelberg, Germany .
    Linseisen, Jakob
    German Cancer Research Center, Heidelberg, Germany .
    Beckmann, Lars
    German Cancer Research Center, Heidelberg, Germany .
    Müller-Decker, Karin
    German Cancer Research Center, Heidelberg, Germany .
    Canzian, Federico
    German Cancer Research Center, Heidelberg, Germany.
    Hüsing, Anika
    German Cancer Research Center, Heidelberg, Germany.
    Kaaks, Rudolf
    German Cancer Research Center, Heidelberg, Germany.
    Vogel, Ulla
    National Food Institute, Technical University of Denmark, Soborg, Denmark.
    Jakobsen, Marianne Uhre
    Department of Clinical Epidemiology, Aarhus University Hospital, Aalborg, Denmark.
    Overvad, Kim
    Department of Clinical Epidemiology, Aarhus University Hospital, Aalborg, Denmark.
    Hansen, Rikke Dalgaard
    Danish Cancer Society, Copenhagen, Denmark.
    Knüppel, Sven
    Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany.
    Boeing, Heiner
    Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany.
    Trichopoulou, Antonia
    Department of Hygiene and Epidemiology, University of Athens Medical School, Athens, Greece .
    Yvoni, Koumantaki
    Department of Hygiene and Epidemiology, University of Athens Medical School, Athens, Greece.
    Trichopoulos, Dimitrios
    Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA .
    Berrino, Franco
    Etiological Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy .
    Palli, Domenico
    Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy .
    Panico, Salvatore
    Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy .
    Tumino, Rosario
    Cancer Registry and Histopathology Unit, Department of Oncology , “Civile - M.P.Arezzo” Hospital, Ragusa, Italy .
    Bueno-de-Mesquita, H Bas
    National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands .
    van Duijnhoven, Fränzel J B
    National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands .
    van Gils, Carla H
    Julius Center, University Medical Center Utrecht, Utrecht, The Netherlands .
    Peeters, Petra H
    Julius Center, University Medical Center Utrecht, Utrecht, The Netherlands .
    Dumeaux, Vanessa
    Institute of Community Medicine, University of Tromsø, Norway .
    Lund, Eiliv
    Institute of Community Medicine, University of Tromsø, Norway .
    Huerta Castaño, José M
    CIBER Epidemiología y Salud Pública, CIBERESP, Spain .
    Muñoz, Xavier
    Research Laboratory and Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain .
    Rodriguez, Laudina
    Public Health and Participation Directorate, Health and Health Care Services Council, Asturias, Spain .
    Barricarte, Aurelio
    CIBER Epidemiología y Salud Pública, CIBERESP, Spain .
    Manjer, Jonas
    Department of Surgery, Malmö University Hospital, Malmö, Sweden .
    Jirström, Karin
    Center for Molecular Pathology, Department of Laboratory Medicine, Malmö University Hospital, Lund University, Malmö Sweden .
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Spencer, Elizabeth A
    Cancer Epidemiology Unit, University of Oxford, Oxford, UK .
    Crowe, Francesca L
    Cancer Epidemiology Unit, University of Oxford, Oxford, UK .
    Khaw, Kay-Tee
    Department of Public Health and Primary Care, University of Cambridge .
    Wareham, Nick
    Medical Research Council (MRC) Epidemiology Unit, Cambridge, UK .
    Morois, Sophie
    Inserm, (Institut National de la Santé et de la Recherche Médicale), and Institut Gustave Roussy, Villejuif, France .
    Boutron-Ruault, Marie-Christine
    Inserm, (Institut National de la Santé et de la Recherche Médicale), and Institut Gustave Roussy, Villejuif, France .
    Clavel-Chapelon, Françoise
    Inserm, (Institut National de la Santé et de la Recherche Médicale), and Institut Gustave Roussy, Villejuif, France .
    Chajes, Veronique
    International Agency for Research on Cancer (IARC), Lyon, France .
    Jenab, Mazda
    International Agency for Research on Cancer (IARC), Lyon, France .
    Boffetta, Paolo
    International Agency for Research on Cancer (IARC), Lyon, France .
    Vineis, Paolo
    Cancer Epidemiology Department, University of Turin, Turin, Italy .
    Mouw, Traci
    Division of Epidemiology, Public Health and Primary Care, Imperial College London, London, UK .
    Norat, Teresa
    Division of Epidemiology, Public Health and Primary Care, Imperial College London, London, UK .
    Riboli, Elio
    Division of Epidemiology, Public Health and Primary Care, Imperial College London, London, UK .
    Nieters, Alexandra
    German Cancer Research Center, Heidelberg, Germany .
    Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk.2010In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 31, no 3, p. 466-472Article in journal (Refereed)
    Abstract [en]

    Colorectal cancer is the third most common malignant tumor and the fourth-leading cause of cancer death worldwide. The crucial role of fatty acids for a number of important biological processes suggests a more in depth analysis of inter-individual differences in fatty acid metabolizing genes as contributing factor to colon carcinogenesis. We examined the association between genetic variability in 43 fatty acid metabolism-related genes and colorectal risk in 1225 CRC cases and 2032 controls participating in the European Prospective Investigation into Cancer and Nutrition study. 392 single nucleotide polymorphisms were selected using pairwise tagging with an r(2) cutoff of 0.8 and a minor allele frequency of >5%. Conditional logistic regression models were used to estimate odds ratios and corresponding 95% confidence intervals. Haplotype analysis was performed using a generalized linear model framework. On the genotype level, HPGD, PLA2G6, and TRPV3 were associated with higher risk for colorectal cancer, while PTGER2 was associated with lower colorectal cancer risk. A significant inverse association (p < 0.006) was found for PTGER2 GGG haplotype while HPGD AGGAG and PLA2G3 CT haplotypes were significantly (p < 0.001 and p = 0.003, respectively) associated with higher risk of colorectal cancer. Based on these data we present for the first time the association of HPGD variants with colorectal cancer risk. Our results support the key role of prostanoid signaling in colon carcinogenesis and suggest a relevance of genetic variation in fatty acid metabolism-related genes and colorectal cancer risk.

  • 230. Holl, Katsiaryna
    et al.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Kaasila, Marjo
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Afanasyeva, Yelena
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lehtinen, Matti
    Pukkala, Eero
    Surcel, Helja-Marja
    Toniolo, Paolo
    Zeleniuch-Jacquotte, Anne
    Koskela, Pentti
    Lukanova, Annekatrin
    Effect of long-term storage on hormone measurements in samples from pregnant women: the experience of the Finnish Maternity Cohort2008In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 47, no 3, p. 406-412Article in journal (Refereed)
    Abstract [en]

    Validity of biobank studies on hormone associated cancers depend on the extent the sample preservation is affecting the hormone measurements. We investigated the effect of long-term storage (up to 22 years) on immunoassay measurements of three groups of hormones and associated proteins: sex-steroids [estradiol, progesterone, testosterone, dihydroepiandrosterone sulphate (DHEAS), sex hormone-binding globulin (SHBG)], pregnancy-specific hormones [human chorionic gonadotropin (hCG), placental growth hormone (pGH), alpha-fetoprotein (AFP)], and insulin-like growth factor (IGF) family hormones exploiting the world largest serum bank, the Finnish Maternity Cohort (FMC). Hormones of interest were analyzed in a random sample of 154 Finnish women in the median age (29.5 years, range 25 to 34 years) of their first pregnancy with serum samples drawn during the first trimester. All hormone measurements were performed using commercial enzyme-linked- or radio-immunoassays. Storage time did not correlate with serum levels of testosterone, DHEAS, hCG, pGH and total IGFBP-1. It had a weak or moderate negative correlation with serum levels of progesterone (Spearman's ranked correlation coefficient (rs)=− 0.36), IGF-I (rs=−0.23) and IGF binding protein (BP)-3 (rs=−0.38), and weak positive correlation with estradiol (rs=0.23), SHBG (rs=0.16), AFP (rs=0.20) and non-phosphorylated IGF binding protein (BP)-1 (rs=0.27). The variation of all hormone levels studied followed the kinetics reported for early pregnancy. Bench-lag time (the time between sample collection and freezing for storage) did not materially affect the serum hormone levels. In conclusion, the stored FMC serum samples can be used to study hormone-disease associations, but close matching for storage time and gestational day are necessary design components of all related biobank studies.

  • 231. Holl, Katsiaryna
    et al.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Surcel, Heljä-Marja
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Koskela, Pentti
    Dillner, Joakim
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Olafsdottir, Gudridur H
    Ogmundsdottir, Helga M
    Pukkala, Eero
    Lehtinen, Matti
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Lukanova, Annekatrin
    Endogenous steroid hormone levels in early pregnancy and risk of testicular cancer in the offspring: A nested case-referent study.2009In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 124, no 12, p. 2923-2928Article in journal (Refereed)
    Abstract [en]

    According to the leading hypothesis on testicular cancer (TC) etiology exposure to a specific pattern of steroid hormones in utero, in particular, to high levels of estrogens and low levels of androgens is the major determinant of TC risk in the offspring. We performed a case-referent study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of maternal endogenous steroid hormones with regard to the risk of TC. TC cases and referents were aged between 0 and 25 years. For each case-index mother pair, three or four matched referent-referent mother pairs were identified using national population registries. First trimester or early second trimester sera were retrieved from the index mothers of 73 TC cases and 286 matched referent mothers, and were tested for dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, estradiol, estrone, and sex hormone binding globulin (SHBG). Offspring of mothers with high DHEAS levels had a significantly decreased risk of TC (OR for highest vs. lowest DHEAS quartile, 0.18 (95% CI 0.06-0.58). In contrast, offspring of mothers with high androstenedione levels had an increased risk of TC (OR 4.1; 95% CI 1.2-12.0). High maternal total estradiol level also tended to be associated with an increased risk of TC in the offspring (OR 32; 95% CI 0.98-1,090). We report the first direct evidence that interplay of maternal steroid hormones in the early pregnancy is important in the etiology of TC in the offspring. (c) 2009 UICC.

  • 232. Holl, Katsiaryna
    et al.
    Surcel, Helja-Marja
    Koskela, Pentti
    Dillner, Joakim
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Kaasila, Marjo
    Olafsdottir, Gudridur H
    Ogmundsdottir, Helga M
    Pukkala, Eero
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Lehtinen, Matti
    Maternal Epstein-Barr virus and cytomegalovirus infections and risk of testicular cancer in the offspring: a nested case-control study2008In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 116, no 9, p. 816-822Article in journal (Refereed)
    Abstract [en]

    During recent decades the incidence of testicular cancer (TC) has increased rapidly around the world. Associated exogenous etiological factors might therefore be identifiable. We performed a case-control study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of congenital or neonatal infections with Epstein-Barr virus (EBV) and cytomegalovirus (CMV) as risk factors of TC in the offspring. For each case-index mother pair, three or four matched control-control mother pairs were identified using national population registries. First trimester sera were retrieved from the index mothers of 66 TC cases and 258 matched control mothers, and were tested for antibodies to EBV and CMV. High level of maternal EBV IgG antibodies was associated with significantly increased risk of TC in the offspring (odds ratio (OR), 2.50; 95% confidence interval (CI), 1.15, 5.40), especially with risk of non-seminoma TC (OR, 2.73; 950% CI, 1.25, 5.99) and non-seminoma TC diagnosed under 8 years of age (OR, 2.72; 95% CI, 1.05, 7.04). In contrast, offspring of CMV IgG-seropositive mothers had a decreased risk of TC diagnosed under 8 years of age (OR, 0.35; 95% CI, 0.14, 0.89). Our results suggest that EBV and CMV infections may be associated with TC.

  • 233.
    Holmström, Benny
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Johansson, Mattias
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. International Agency for Research on Cancer (IARC), Lyon, France.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Stenman, Ulf-Håkan
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Prostate specific antigen for early detection of prostate cancer: longitudinal study2009In: BMJ (Clinical research ed.), ISSN 1468-5833, Vol. 339, p. b3537-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate if prostate specific antigen test attains validity standards required for screening in view of recent prostate cancer screening trial results.

    DESIGN: Case-control study nested in longitudinal cohort.

    SETTING: Västerbotten Intervention Project cohort, Umeå, Sweden.

    PARTICIPANTS: 540 cases and 1034 controls matched for age and date of blood draw.

    MAIN OUTCOME MEASURE: Validity of prostate specific antigen for prediction of subsequent prostate cancer diagnosis by record linkage to cancer registry.

    RESULTS: Blood samples were drawn on average 7.1 (SD 3.7) years before diagnosis. The area under the curve for prostate specific antigen was 0.84 (95% confidence interval 0.82 to 0.86). At prostate specific antigen cut-off values of 3, 4, and 5 ng/ml, sensitivity estimates were 59%, 44%, and 33%, and specificity estimates were 87%, 92%, and 95%. The positive likelihood ratio commonly considered to "rule in disease" is 10; in this study the positive likelihood ratios were 4.5, 5.5, and 6.4 for prostate specific antigen cut-off values of 3, 4, and 5 ng/ml. The negative likelihood ratio commonly considered to "rule out disease" is 0.1; in this study the negative likelihood ratios were 0.47, 0.61, and 0.70 for prostate specific antigen cut-off values of 3, 4, and 5 ng/ml. For a cut-off of 1.0 ng/ml, the negative likelihood ratio was 0.08.

    CONCLUSIONS: No single cut-off value for prostate specific antigen concentration attained likelihood ratios formally required for a screening test. Prostate specific antigen concentrations below 1.0 ng/ml virtually ruled out a prostate cancer diagnosis during the follow-up. Additional biomarkers for early detection of prostate cancer are needed before population based screening for prostate cancer should be introduced.

  • 234. Hruby, Adela
    et al.
    Ngwa, Julius S.
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wojczynski, Mary K.
    Ganna, Andrea
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Houston, Denise K.
    Jacques, Paul F.
    Kanoni, Stavroula
    Lehtimaki, Terho
    Lemaitre, Rozenn N.
    Manichaikul, Ani
    North, Kari E.
    Ntalla, Ioanna
    Sonestedt, Emily
    Tanaka, Toshiko
    van Rooij, Frank J. A.
    Bandinelli, Stefania
    Djousse, Luc
    Grigoriou, Efi.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Lohman, Kurt K.
    Pankow, James S.
    Raitakari, Olli T.
    Riserus, Ulf
    Yannakoulia, Mary
    Zillikens, M. Carola
    Hassanali, Neelam
    Liu, Yongmei
    Mozaffarian, Dariush
    Papoutsakis, Constantina
    Syvanen, Ann-Christine
    Uitterlinden, Andre G.
    Viikari, Jorma
    Groves, Christopher J.
    Hofman, Albert
    Lind, Lars
    McCarthy, Mark I.
    Mikkila, Vera
    Mukamal, Kenneth
    Franco, Oscar H.
    Borecki, Ingrid B.
    Cupples, L. Adrienne
    Dedoussis, George V.
    Ferrucci, Luigi
    Hu, Frank B.
    Ingelsson, Erik
    Kahonen, Mika
    Kao, W. H. Linda
    Kritchevsky, Stephen B.
    Orho-Melander, Marju
    Prokopenko, Inga
    Rotter, Jerome I.
    Siscovick, David S.
    Witteman, Jacqueline C. M.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Meigs, James B.
    McKeown, Nicola M.
    Nettleton, Jennifer A.
    Higher Magnesium Intake Is Associated with Lower Fasting Glucose and Insulin, with No Evidence of Interaction with Select Genetic Loci, in a Meta-Analysis of 15 CHARGE Consortium Studies2013In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 143, no 3, p. 345-353Article in journal (Refereed)
    Abstract [en]

    Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesium intake and fasting glucose and insulin. Fifteen studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (In-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [beta = -0.009 mmol/L (95% CI: -0.013, -0.005), P< 0.0001] and insulin (-0.020 In-pmo/L (95% CI: -0.024, -0.017), P< 0.0001]. No magnesium-related SNP or interaction between any SNP and magnesium reached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P= 0.03) with glucose, and rs11558471 in SLC30A8and rs3740393 near CNNM2showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted. J. Nutr. 143: 345-353, 2013.

  • 235. Hughes, David J
    et al.
    Fedirko, Veronika
    Jenab, Mazda
    Schomburg, Lutz
    Méplan, Catherine
    Freisling, Heinz
    Bueno-de-Mesquita, H B As
    Hybsier, Sandra
    Becker, Niels-Peter
    Czuban, Magdalena
    Tjønneland, Anne
    Outzen, Malene
    Boutron-Ruault, Marie-Christine
    Racine, Antoine
    Bastide, Nadia
    Kühn, Tilman
    Kaaks, Rudolf
    Trichopoulos, Dimitrios
    Trichopoulou, Antonia
    Lagiou, Pagona
    Panico, Salvatore
    Peeters, Petra H
    Weiderpass, Elisabete
    Skeie, Guri
    Dagrun, Engeset
    Chirlaque, Maria-Dolores
    Sánchez, Maria-Jose
    Ardanaz, Eva
    Ljuslinder, Ingrid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Bradbury, Kathryn E
    Vineis, Paolo
    Naccarati, Alessio
    Palli, Domenico
    Boeing, Heiner
    Overvad, Kim
    Dorronsoro, Miren
    Jakszyn, Paula
    Cross, Amanda J
    Quirós, Jose Ramón
    Stepien, Magdalena
    Kong, So Yeon
    Duarte-Salles, Talita
    Riboli, Elio
    Hesketh, John E
    Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort.2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 136, no 5, p. 1149-1161Article in journal (Refereed)
    Abstract [en]

    Suboptimal intakes of the micronutrient selenium (Se) are found in many parts of Europe. Low Se status may contribute to colorectal cancer (CRC) development. We assessed Se status by measuring serum levels of Se and Selenoprotein P (SePP) and examined the association with CRC risk in a nested case-control design (966 CRC cases; 966 matched controls) within the European Prospective Investigation into Cancer and Nutrition. Se was measured by total reflection X-ray fluorescence and SePP by immunoluminometric sandwich assay. Multivariable incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Respective mean Se and SePP levels were 84.0 μg/L and 4.3 mg/L in cases and 85.6 μg/L and 4.4 mg/L in controls. Higher Se concentrations were associated with a non-significant lower CRC risk (IRR = 0.92, 95% CI: 0.82-1.03 per 25 μg/L increase). However, sub-group analyses by sex showed a statistically significant association for women (ptrend  = 0.032; per 25 μg/L Se increase, IRR = 0.83, 95% CI: 0.70-0.97) but not for men. Higher SePP concentrations were inversely associated with CRC risk (ptrend  = 0.009; per 0.806 mg/L increase, IRR = 0.89, 95% CI: 0.82-0.98) with the association more apparent in women (ptrend  = 0.004; IRR = 0.82, 95% CI: 0.72-0.94 per 0.806 mg/L increase) than men (ptrend  = 0.485; IRR = 0.98, 95% CI: 0.86-1.12 per 0.806 mg/L increase). The findings indicate that Se status is suboptimal in many Europeans and suggest an inverse association between CRC risk and higher serum Se status, which is more evident in women.

  • 236.
    Hultdin, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Thøgersen, Ann Margreth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, T K
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Elevated plasma homocysteine: cause or consequence of myocardial infarction?2004In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 256, no 6, p. 491-498Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To determine whether a first myocardial infarction leads to increased plasma homocysteine concentrations and whether the association between homocysteine and myocardial infarction was greater at follow-up compared with baseline. DESIGN: A population-based, prospective, nested case-referent study. SETTING: Screening took place at the nearest health survey centre in northern Sweden. SUBJECTS: Of more than 36,000 persons screened, 78 developed a first myocardial infarction (average 18 months after sampling). Fifty of these had participated in a follow-up health survey (average 8(1/2) years between surveys) and were sex- and age-matched with 56 referents. MAIN OUTCOME MEASURES: Comparison of plasma homocysteine levels in case and referent subjects before and after development of a first myocardial infarction. RESULTS: No statistically significant difference was found between cases and referents regarding homocysteine at baseline or follow-up. Plasma homocysteine and plasma creatinine increased significantly, and plasma albumin decreased significantly over time. Conditional univariate logistic regression indicated that high homocysteine at follow-up but not baseline was associated with first myocardial infarction (OR 2.49; 95% CI: 1.03-6.02), but the relation disappeared in multivariate analyses including plasma creatinine and plasma albumin. High plasma creatinine remained associated with first myocardial infarction at both baseline (OR 2.94; 95% CI: 1.05-8.21) and follow-up (OR 3.38; 95% CI: 1.21-9.48). CONCLUSION: In this study, first myocardial infarction did not cause increased plasma homocysteine concentration.

  • 237.
    Hultdin, Johan
    et al.
    Umeå University, Faculty of Medicine, Medical Biosciences, Clinical chemistry.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Nutritional Research.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology.
    Plasma folate, vitamin B12, and homocysteine and prostate cancer risk: a prospective study.2005In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 113, no 5, p. 819-824Article in journal (Refereed)
    Abstract [en]

    The role of folate metabolism in cancer development is a topic of much current interest, with maintenance of adequate folate status tending to show a protective effect. Aberrant methylation, primarily hypermethylation of certain genes including tumor suppressors, has been implicated in prostate cancer development. Folate, vitamin B12 and homocysteine are essential for methyl group metabolism and thus also for DNA methylation. We related plasma levels of these factors to prostate cancer risk in a prospective study of 254 case subjects and 514 matched control subjects. Increasing plasma levels of folate and vitamin B12 were statistically significantly associated with increased prostate cancer risk, with an odds ratio of 1.60 (95% CI = 1.03-2.49; p(trend) = 0.02) for folate and 2.63 (95% CI = 1.61-4.29; p(trend) < 0.001) for vitamin B12 for highest vs. lowest quartile. Increasing plasma homocysteine levels were associated with a reduced risk of borderline significance (OR = 0.67; 95% CI = 0.43-1.04; p(trend) = 0.08). After adjustment for the other 2 plasma variables, body mass index and smoking, a statistically significant increased risk remained only for vitamin B12 (OR = 2.96; 95% CI = 1.58-5.55; p(trend) = 0.001). Adjusted OR for folate and homocysteine were 1.30 (95% CI = 0.74-2.24; p(trend) = 0.17) and 0.91 (95% CI = 0.51-1.58; p(trend) = 0.60), respectively. Our results suggest that factors contributing to folate status are not protective against prostate cancer. On the contrary, vitamin B12, associated with an up to 3-fold increase in risk, and possibly also folate, may even stimulate prostate cancer development. These findings are novel and should be explored further in future studies. (c) 2004 Wiley-Liss, Inc.

  • 238.
    Hultdin, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Winkvist, Anna
    Department of Clinical Nutrition, Göteborg University, Gothenburg, Sweden.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Torbjörn K.
    Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Prospective study of first stroke in relation to plasma homocysteine and MTHFR 677C > T and 1298A > C genotypes and haplotypes: evidence for an association with hemorrhagic stroke2011In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 49, no 9, p. 1555-1562Article in journal (Refereed)
    Abstract [en]

    Background: Abnormalities in homocysteine metabolism have been suggested as risk factors for stroke. The aim of this prospective study was to examine whether total plasma homocysteine concentration (tHcy) and its main genetic determinant, methylene tetrahydrofolate reductase (MTHFR) polymorphisms, were associated with first ischemic or hemorrhagic stroke.

    Methods: This was a nested case-referent study of 321 ischemic and 60 hemorrhagic stroke cases, defined by WHO MONICA criteria and each matched with two event-free referents for sex, age, cohort, recruitment date and geographical area. All subjects were from the population-based Northern Sweden Health and Disease Study cohorts. Odds ratios were determined by conditional logistic regression.

    Results: The mean follow-up time was 4.2 years. Both tHcy and MTHFR were independent predictors of hemorrhagic stroke in multivariate models including body mass index, hypertension and, for MTHFR, tHcy [OR for the highest vs. lowest tHcy quartile 8.13 (95% CI 1.83-36.1), p(trend)=0.002; OR for MTHFR 677TT vs. 677CC genotype 3.62 (95% CI 0.77-17.0), p(trend)=0.040]. Haplotype analyses confirmed that the MTHFR 677T-1298A haplotype was positively associated with hemorrhagic stroke [OR 1.81 (95% CI 1.09-3.00), p=0.022], whereas the MTHFR 677C-1298C haplotype was not significantly related to either hemorrhagic or ischemic stroke. Neither tHcy nor the MTHFR polymorphisms were significant predictors of ischemic stroke.

    Conclusion: Both elevated plasma homocysteine levels and the MTHFR 677T allele are indicators of increased risk of hemorrhagic stroke in the northern Swedish population.

  • 239. Hunt, Kelly J
    et al.
    Lukanova, Annekatrin
    Rinaldi, Sabina
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Norat, Teresa
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Riboli, Elio
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Kaaks, Rudolf
    A potential inverse association between insulin-like growth factor I and hypertension in a cross-sectional study.2006In: Annals of Epidemiology, ISSN 1047-2797, E-ISSN 1873-2585, Vol. 16, no 7, p. 563-571Article in journal (Refereed)
  • 240. Huseinovic, E.
    et al.
    Winkvist, A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Department of Internal Medicine and Clinical Nutrition, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Slimani, N.
    Park, M. K.
    Freisling, H.
    Boeing, H.
    Buckland, G.
    Schwingshackl, L.
    Weiderpass, E.
    Rostgaard-Hansen, A. L.
    Tjønneland, A.
    Affret, A.
    Boutron-Ruault, M. C.
    Fagherazzi, G.
    Katzke, V.
    Kühn, T.
    Naska, A.
    Orfanos, P.
    Trichopoulou, A.
    Pala, V.
    Palli, D.
    Ricceri, F.
    Santucci de Magistris, M.
    Tumino, R.
    Engeset, D.
    Enget, T.
    Skeie, G.
    Barricarte, A.
    Bonet, C. B.
    Chirlaque, M. D.
    Amiano, P.
    Quirós, J. R.
    Sánchez, M. J.
    Dias, J. A.
    Drake, I.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Boer, J. M. A.
    Ocké, M. C.
    Verschuren, W. M. M.
    Lassale, C.
    Perez-Cornago, A.
    Riboli, E.
    Ward, H.
    Bertéus Forslund, H.
    Meal patterns across ten European countries: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study2016In: Public Health Nutrition, ISSN 1368-9800, E-ISSN 1475-2727, Vol. 19, no 15, p. 2769-2780Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To characterize meal patterns across ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study.

    DESIGN: Cross-sectional study utilizing dietary data collected through a standardized 24 h diet recall during 1995-2000. Eleven predefined intake occasions across a 24 h period were assessed during the interview. In the present descriptive report, meal patterns were analysed in terms of daily number of intake occasions, the proportion reporting each intake occasion and the energy contributions from each intake occasion.

    SETTING: Twenty-seven centres across ten European countries.

    SUBJECTS: Women (64 %) and men (36 %) aged 35-74 years (n 36 020).

    RESULTS: Pronounced differences in meal patterns emerged both across centres within the same country and across different countries, with a trend for fewer intake occasions per day in Mediterranean countries compared with central and northern Europe. Differences were also found for daily energy intake provided by lunch, with 38-43 % for women and 41-45 % for men within Mediterranean countries compared with 16-27 % for women and 20-26 % for men in central and northern European countries. Likewise, a south-north gradient was found for daily energy intake from snacks, with 13-20 % (women) and 10-17 % (men) in Mediterranean countries compared with 24-34 % (women) and 23-35 % (men) in central/northern Europe.

    CONCLUSIONS: We found distinct differences in meal patterns with marked diversity for intake frequency and lunch and snack consumption between Mediterranean and central/northern European countries. Monitoring of meal patterns across various cultures and populations could provide critical context to the research efforts to characterize relationships between dietary intake and health.

  • 241. Huseinovic, Ena
    et al.
    Winkvist, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Department of Internal Medicine and Clinical Nutrition, The Sahlgrenska Academy, University of Gothenburg, Box 459, SE-405 30, Gothenburg, Sweden.
    Freisling, Heinz
    Slimani, Nadia
    Boeing, Heiner
    Buckland, Genevieve
    Schwingshackl, Lukas
    Olsen, Anja
    Tjønneland, Anne
    Stepien, Magdalena
    Boutron-Ruault, Marie-Christine
    Mancini, Francesca
    Artaud, Fanny
    Kühn, Tilman
    Katzke, Verena
    Trichopoulou, Antonia
    Naska, Androniki
    Orfanos, Philippos
    Tumino, Rosario
    Masala, Giovanna
    Krogh, Vittorio
    Santucci de Magistris, Maria
    Ocké, Marga C
    Brustad, Magritt
    Jensen, Torill Enget
    Skeie, Guri
    Rodríguez-Barranco, Miguel
    Huerta, José María
    Ardanaz, Eva
    Quirós, José Ramón
    Jakszyn, Paula
    Sonestedt, Emily
    Ericson, Ulrika
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Key, Timothy J
    Aune, Dagfinn
    Riboli, Elio
    Weiderpass, Elisabete
    Bertéus Forslund, Heléne
    Timing of eating across ten European countries: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study2019In: Public Health Nutrition, ISSN 1368-9800, E-ISSN 1475-2727, Vol. 22, no 2, p. 324-335Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine timing of eating across ten European countries.

    DESIGN: Cross-sectional analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study using standardized 24 h diet recalls collected during 1995-2000. Eleven predefined food consumption occasions were assessed during the recall interview. We present time of consumption of meals and snacks as well as the later:earlier energy intake ratio, with earlier and later intakes defined as 06.00-14.00 and 15.00-24.00 hours, respectively. Type III tests were used to examine associations of sociodemographic, lifestyle and health variables with timing of energy intake.

    SETTING: Ten Western European countries.

    SUBJECTS: In total, 22 985 women and 13 035 men aged 35-74 years (n 36 020).

    RESULTS: A south-north gradient was observed for timing of eating, with later consumption of meals and snacks in Mediterranean countries compared with Central and Northern European countries. However, the energy load was reversed, with the later:earlier energy intake ratio ranging from 0·68 (France) to 1·39 (Norway) among women, and from 0·71 (Greece) to 1·35 (the Netherlands) among men. Among women, country, age, education, marital status, smoking, day of recall and season were all independently associated with timing of energy intake (all P<0·05). Among men, the corresponding variables were country, age, education, smoking, physical activity, BMI and day of recall (all P<0·05).

    CONCLUSIONS: We found pronounced differences in timing of eating across Europe, with later meal timetables but greater energy load earlier during the day in Mediterranean countries compared with Central and Northern European countries.

  • 242. Hvidtfeldt, Ulla A
    et al.
    Tolstrup, Janne S
    Jakobsen, Marianne U
    Heitmann, Berit L
    Grønbaek, Morten
    O'Reilly, Eilis
    Bälter, Katarina
    Goldbourt, Uri
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Knekt, Paul
    Liu, Simin
    Pereira, Mark
    Pietinen, Pirjo
    Spiegelman, Donna
    Stevens, June
    Virtamo, Jarmo
    Willett, Walter C
    Rimm, Eric B
    Ascherio, Alberto
    Alcohol intake and risk of coronary heart disease in younger, middle-aged, and older adults2010In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 121, no 14, p. 1589-1597Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Light to moderate alcohol consumption is associated with a reduced risk of coronary heart disease. This protective effect of alcohol, however, may be confined to middle-aged or older individuals. Coronary heart disease incidence is low in men <40 years of age and in women <50 years of age; for this reason, study cohorts rarely have the power to investigate the effects of alcohol on coronary heart disease risk in younger adults. This study examined whether the beneficial effect of alcohol on coronary heart disease depends on age. METHODS AND RESULTS: In this pooled analysis of 8 prospective studies from North America and Europe including 192,067 women and 74,919 men free of cardiovascular diseases, diabetes, and cancers at baseline, average daily alcohol intake was assessed at baseline with a food frequency or diet history questionnaire. An inverse association between alcohol and risk of coronary heart disease was observed in all age groups; hazard ratios among moderately drinking men (5.0 to 29.9 g/d) 39 to 50, 50 to 59, and >or=60 years of age were 0.58 (95% confidence interval [CI], 0.36 to 0.93), 0.72 (95% CI, 0.60 to 0.86), and 0.85 (95% CI, 0.75 to 0.97) compared with abstainers. However, the analyses indicated a smaller incidence rate difference between abstainers and moderate consumers in younger adults (incidence rate difference, 45 per 100,000; 90% CI, 8 to 84) than in middle-aged (incidence rate difference, 64 per 100,000; 90% CI, 24 to 102) and older (incidence rate difference, 89 per 100,000; 90% CI, 44 to 140) adults. Similar results were observed in women. CONCLUSIONS: Alcohol is also associated with a decreased risk of coronary heart disease in younger adults; however, the absolute risk was small compared with middle-aged and older adults.

  • 243.
    Häggstrom, Christel
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Ulmert, David
    Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Malmö, Sweden.
    Bjørge, Tone
    Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
    Ulmer, Hanno
    nnsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, Innsbruck, Austria.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Manjer, Jonas
    Lund Univ, Dept Plast Surg, Skåne Univ Hosp, Malmö, Sweden.
    Engeland, Anders
    Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
    Nagel, Gabriele
    Univ Ulm, Inst Epidemiol & Med Biometry, Ulm, Germany.
    Almqvist, Martin
    Lund Univ, Skåne Univ Hosp, Dept Surg, Malmö, Sweden.
    Selmer, Randi
    Norwegian Inst Publ Hlth, Oslo, Norway.
    Concin, Hans
    Agcy Prevent & Social Med, Bregenz, Austria.
    Tretli, Steinar
    Canc Registry Norway, Inst Populat Based Canc Res, Oslo, Norway.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Prospective study on metabolic factors and risk of prostate cancer2012In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 118, no 24, p. 6199-6206Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There are inconsistent data regarding the association between metabolic factors, separately and combined, and the risk of prostate cancer and death from prostate cancer.

    METHODS: In the Metabolic Syndrome and Cancer Project (Me-Can), data on body mass index (BMI); blood pressure; and blood levels of glucose, cholesterol, and triglycerides were collected for 289,866 men. Cox proportional hazard models were used to calculate relative risks (RRs) by exposures in quintiles as well as for z scores (with a mean of 0 and a standard deviation of 1) together with a composite sum of scores to assess the combined effect of metabolic factors. RRs were corrected for random errors in measurement.

    RESULTS: During a mean follow-up of 12 years, 6673 men were diagnosed with prostate cancer and 961 died of the disease. Men with high levels of glucose and triglycerides were found to have a decreased risk of prostate cancer: top versus bottom quintile of glucose: RR, 0.82 (95% confidence interval [95% CI], 0.62-1.08; P value for trend = .03) and top versus bottom quintile of triglycerides: RR, 0.88 (95% CI, 0.74-1.04; P value for trend = .001). High BMI, elevated blood pressure, and a high composite z score were found to be associated with an increased risk of death from prostate cancer: top versus bottom quintile of BMI: RR, 1.36 (95% CI, 1.08-1.71); systolic blood pressure: RR, 1.62 (95% CI, 1.07-2.45); and per 1-unit increase of the composite z score: RR, 1.13 (95% CI, 1.03-1.25).

    CONCLUSIONS: The authors found no evidence of an association between high levels of metabolic factors and the risk of prostate cancer, but high BMI, elevated blood pressure, and a composite score of all metabolic factors were associated with an increased risk of death from prostate cancer. 

  • 244.
    Häggström, Christel
    et al.
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden..
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bjørge, Tone
    Nagel, Gabriele
    Manjer, Jonas
    Ulmer, Hanno
    Drake, Isabel
    Ghaderi, Sara
    Lang, Alois
    Engeland, Anders
    Stattin, Pär
    Stocks, Tanja
    Linear age-course effects on the associations between body mass index, triglycerides, and female breast and male liver cancer risk: An internal replication study of 800,000 individuals2020In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 146, no 1, p. 58-67Article in journal (Refereed)
    Abstract [en]

    Apart from the consistently observed differential association between obesity and breast cancer risk by menopausal status, the associations between obesity and other metabolic imbalances with risks of cancers have not been systematically investigated across the age‐course. We created two random 50–50% cohorts from six European cohorts comprising 813,927 individuals. In the “discovery cohort”, we used Cox regression with attained age as time‐scale and tested interactions between body mass index (BMI), blood pressure, plasma glucose, triglycerides and cholesterol, and attained age in relation to cancer risk. Results with a p‐value below 0.05 were additionally tested in the “replication cohort” where a replicated result was considered evidence of a linear interaction with attained age. These findings were investigated by flexible parametric survival models for any age‐plateaus in their shape of associations with cancer risk across age. Consistent with other studies, BMI was negatively related to breast cancer risk (n cases = 11,723) among younger (premenopausal) women. However, the association remained negative for several years after menopause and, although gradually weakening over age, the association became positive only at 62 years of age. This linear and positive age‐interaction was also found for triglycerides and breast cancer, and for BMI and triglycerides in relation to liver cancer among men (n cases = 444). These findings are unlikely to be due to chance owing to the replication. The linear age‐interactions in breast cancer may suggest an influence by other age‐related factors than menopause; however, further investigation of age‐related effect modifiers in both breast and liver cancer is needed.

  • 245.
    Häggström, Christel
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Rapp, Kilian
    Univ Ulm, Inst Epidemiol & Med Biometry, D-89069 Ulm, Germany.
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Manjer, Jonas
    Lund Univ, Skåne Univ Hosp, Dept Surg, Malmö, Sweden.
    Bjørge, Tone
    Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
    Ulmer, Hanno
    Med Univ Innsbruck, Dept Med Stat Informat & Hlth Econ, A-6020 Innsbruck, Austria.
    Engeland, Anders
    Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
    Almqvist, Martin
    Lund Univ, Skåne Univ Hosp, Dept Surg, Malmö, Sweden.
    Concin, Hans
    Agcy Prevent & Social Med, Bregenz, Australia.
    Selmer, Randi
    Norwegian Inst Publ Hlth, Oslo, Norway.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Tretli, Steinar
    Canc Registry Norway, Inst Populat Based Canc Res, Oslo, Norway.
    Nagel, Gabriele
    Univ Ulm, Inst Epidemiol & Med Biometry, D-89069 Ulm, Germany.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Metabolic factors associated with risk of renal cell carcinoma2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 2, p. e57475-Article in journal (Refereed)
    Abstract [en]

    Previous studies have shown that obesity and hypertension are associated with increased risk of renal cell carcinoma (RCC), but less is known about the association to other metabolic factors. In the Metabolic Syndrome and Cancer project (Me-Can) data on body mass index (BMI, kg/m2), blood pressure, and circulating levels of glucose, cholesterol, and triglycerides were collected from 560,388 men and women in cohorts from Norway, Austria, and Sweden. By use of Cox proportional hazard models, hazard ratios (HR) were calculated for separate and composite metabolic exposures. During a median follow-up of 10 years, 592 men and 263 women were diagnosed with RCC. Among men, we found an increased risk of RCC for BMI, highest vs. lowest quintile, (HR = 1.51, 95% CI 1.13-2.03), systolic blood pressure, (HR = 3.40, 95% CI 1.91-6.06), diastolic blood pressure, (HR = 3.33, 95% CI 1.85-5.99), glucose, (HR = 3.75, 95% CI 1.46-9.68), triglycerides, (HR = 1.79, 95% CI 1.00-3.21) and a composite score of these metabolic factors, (HR = 2.68, 95% CI 1.75-4.11). Among women we found an increased risk of RCC for BMI, highest vs. lowest quintile, (HR = 2.21, 95% CI 1.32-3.70) and the composite score, (HR = 2.29, 95% CI 1.12-4.68). High levels of the composite score were also associated with risk of death from RCC among both men and women. No multiplicative statistical or biological interactions between metabolic factors on risk of RCC were found. High levels of BMI, blood pressure, glucose and triglycerides among men and high BMI among women were associated with increased risk of RCC.

  • 246.
    Häggström, Christel
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Nagel, Gabriele
    Manjer, Jonas
    Bjørge, Tone
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Engeland, Anders
    Ulmer, Hanno
    Lindkvist, Bjorn
    Selmer, Randi
    Concin, Hans
    Tretli, Steinar
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Prostate Cancer, Prostate Cancer Death, and Death from Other Causes, Among Men with Metabolic Aberrations2014In: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 25, no 6, p. 823-828Article in journal (Refereed)
    Abstract [en]

    Background: Few previous studies of metabolic aberrations and prostate cancer risk have taken into account the fact that men with metabolic aberrations have an increased risk of death from causes other than prostate cancer. The aim of this study was to calculate, in a real-life scenario, the risk of prostate cancer diagnosis, prostate cancer death, and death from other causes.

    Methods: In the Metabolic Syndrome and Cancer Project, prospective data on body mass index, blood pressure, glucose, cholesterol, and triglycerides were collected from 285,040 men. Risks of prostate cancer diagnosis, prostate cancer death, and death from other causes were calculated by use of competing risk analysis for men with normal (bottom 84%) and high (top 16%) levels of each factor, and a composite score.

    Results: During a mean follow-up period of 12 years, 5,893 men were diagnosed with prostate cancer, 1,013 died of prostate cancer, and 26,328 died of other causes. After 1996, when prostate-specific antigen testing was introduced, men up to age 80 years with normal metabolic levels had 13% risk of prostate cancer, 2% risk of prostate cancer death, and 30% risk of death from other causes, whereas men with metabolic aberrations had corresponding risks of 11%, 2%, and 44%.

    Conclusions: In contrast to recent studies using conventional survival analysis, in a real-world scenario taking risk of competing events into account, men with metabolic aberrations had lower risk of prostate cancer diagnosis, similar risk of prostate cancer death, and substantially higher risk of death from other causes compared with men who had normal metabolic levels.

  • 247.
    Häggström, Christel
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. null.
    Rapp, Kilian
    Univ Ulm, Inst Epidemiol, Ulm, Germany.
    Bjørge, Tone
    Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
    Lindkvist, Björn
    Univ Gothenburg, Sahlgrenska Acad, Dept Med, Gothenburg, Sweden.
    Concin, Hans
    Agcy Prevent & Social Med, Bregenz, Austria.
    Engeland, Anders
    Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
    Manjer, Jonas
    Malmö Univ Hosp, Dept Surg, Malmö, Sweden.
    Ulmer, Hanno
    Innsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, Innsbruck, Austria.
    Selmer, Randi
    Norwegian Inst Publ Hlth, Oslo, Norway.
    Tretli, Steinar
    Canc Registry Norway, Inst Populat Based Canc Res, Oslo, Norway.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research. null.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. null.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. null.
    Metabolic syndrome and risk of bladder cancer: prospective cohort study in the metabolic syndrome and cancer project (Me-Can)2011In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 128, no 8, p. 1890-1898Article in journal (Refereed)
    Abstract [en]

    There are little data on the putative association between factors in the metabolic syndrome (MetS) and risk of bladder cancer. In the Metabolic Syndrome and Cancer project (Me-Can), measurements of height, weight, blood pressure and circulating levels of glucose, cholesterol, and triglycerides had been collected from 578,700 subjects in cohorts in Norway, Austria, and Sweden. We used Cox proportional hazard models to calculate relative risks (RRs) of bladder cancer by exposures divided into quintiles, in categories according to the World Health Organisation (WHO) and as a continuous standardized variable (z-score with mean = 0 and standard deviation = 1) for each separate component and its standardized sum, a composite MetS score. RRs were corrected for random error in measurements. During a mean follow-up of 11.7 years (SD = 7.6), 1,587 men and 327 women were diagnosed with bladder cancer. Significant associations with risk were found among men per one unit increment of z-score for blood pressure, RR = 1.13 (95% CI 1.03-1.25), and the composite MetS score, RR = 1.10 (95% CI 1.01-1.18). Among women, glucose was nonsignificantly associated with risk, RR = 1.41 (95% CI 0.97-2.06). No statistically significant interactions were found between the components in the MetS in relation to bladder cancer risk. Hypertension and a composite MetS score were significantly but modestly associated with an increased risk of bladder cancer among men and elevated glucose was associated with a nonsignificant increase in risk among women.

  • 248.
    Hörnell, Agneta
    et al.
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Winkvist, Anna
    Department of Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg .
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Mis-reporting, previous health status and health status of family may seriously bias the association between food patterns and disease2010In: Nutrition Journal, ISSN 1475-2891, E-ISSN 1475-2891, Vol. 9, no 48Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Food pattern analyses are popular tools in the study of associations between diet and health. However, there is a need for further evaluation of this methodology. The aim of the present cross-sectional study was to evaluate the relationship between food pattern groups (FPG) and existing health, and to identify factors influencing this relationship.

    METHODS: The inhabitants of Västerbotten County in northern Sweden are invited to health check-ups when they turn 30, 40, 50, and 60 years of age. The present study includes data collected from almost 60,000 individuals between 1992 and 2005. Associations between FPG (established using K-means cluster analyses) and health were analyzed separately in men and women.

    RESULTS: The health status of the participants and their close family and reporting accuracy differed significantly between men and women and among FPG. Crude regression analyses, with the high fat FPG as reference, showed increased risks for several health outcomes for all other FPGs in both sexes. However, when limiting analysis to individuals without previous ill-health and with adequate energy intake reports, most of the risks instead showed a trend towards protective effects.

    CONCLUSIONS: Food pattern classifications reflect both eating habits and other own and family health related factors, a finding important to remember and to adjust for before singling out the diet as a primary cause for present and future health problems. Appropriate exclusions are suggested to avoid biases and attenuated associations in nutrition epidemiology.

  • 249.
    Idahl, Annika
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Jurstrand, Margaretha
    Clinical Research Centre, Örebro University Hospital.
    Kumlin, Urban
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Ohlson, Nina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Ottander, Ulrika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Chlamydia trachomatis and Mycoplasma genitalium plasma antibodies in relation to epithelial ovarian tumors2011In: Infectious diseases in obstetrics and gynecology, ISSN 1064-7449, E-ISSN 1098-0997, Vol. 2011, p. 824627-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To assess associations of Chlamydia trachomatis and Mycoplasma genitalium antibodies with epithelial ovarian tumors.

    METHODS: Plasma samples from 291 women, undergoing surgery due to suspected ovarian pathology, were analyzed with respect to C. trachomatis IgG and IgA, chlamydial Heat Shock Protein 60-1 (cHSP60-1) IgG and M. genitalium IgG antibodies. Women with borderline tumors (n=12), ovarian carcinoma (n=45), or other pelvic malignancies (n=11) were matched to four healthy controls each.

    RESULTS: Overall, there were no associations of antibodies with EOC. However, chlamydial HSP60-1 IgG antibodies were associated with type II ovarian cancer (P=.002) in women with plasma samples obtained >1 year prior to diagnosis (n=7). M. genitalium IgG antibodies were associated with borderline ovarian tumors (P=.01).

    CONCLUSION: Chlamydial HSP60-1 IgG and M. genitalium IgG antibodies are in this study associated with epithelial ovarian tumors in some subsets, which support the hypothesis linking upper-genital tract infections and ovarian tumor development.

  • 250. Isaksson, Hanna
    et al.
    Landberg, Rikard
    Sundberg, Birgitta
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Zhang, Jie-Xian
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Tidehag, Per
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Knudsen, Knud Erik Bach
    Moazzami, Ali A.
    Åman, Per
    High-fiber rye diet increases ileal excretion of energy and macronutrients compared with low-fiber wheat diet independent of meal frequency in ileostomy subjects2013In: Food & Nutrition Research, ISSN 1654-6628, E-ISSN 1654-661X, Vol. 57, p. 18519-Article in journal (Refereed)
    Abstract [en]

    Background: Whole-grain foods and cereal dietary fiber intake is associated with lower body weight. This may partly result from lower energy utilization of high-fiber diets. Objective: In the present study, the impact on ileal excretion of energy and macronutrients in response to a rye bread high-fiber diet compared to a refined wheat low-fiber diet was investigated. Furthermore, the effect of meal frequency on apparent absorption of nutrients was studied for the first time. Design: Ten participants that had undergone ileostomy consumed standardized iso-caloric diets, including low-fiber wheat bread (20 g dietary fiber per day) for 2 weeks followed by high-fiber rye bread (52 g dietary fiber per day) for 2 weeks. The diets were consumed in an ordinary (three meals per day) and a nibbling (seven meals per day) meal frequency in a cross-over design. Ileal effluents were collected during 24 h at the third day of each of the four dietary periods and analyzed for gross energy and nutrient contents. Results: The results showed that intake of rye bread high-fiber diet compared to the refined wheat low-fiber diet caused an increase in ileal excretion of energy and macronutrients. The effect was independent of meal frequency. This suggests that a high intake of rye may result in lower availability of macronutrients for small intestinal digestion and absorption. A regular intake of rye may therefore have implications for weight management.

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