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  • 201. Jakszyn, Paula
    et al.
    González, Carlos A
    Luján-Barroso, Leila
    Ros, Martine M
    Bueno-de-Mesquita, H Bas
    Roswall, Nina
    Tjønneland, Anne M
    Büchner, Frederike L
    Egevad, Lars
    Overvad, Kim
    Raaschou-Nielsen, Ole
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Touillaud, Marina S
    Chang-Claude, Jenny
    Allen, Naomi E
    Kiemeney, Lambertus A
    Key, Timothy J
    Kaaks, Rudolf
    Boeing, Heiner
    Weikert, Steffen
    Trichopoulou, Antonia
    Oikonomou, Eleni
    Zylis, Dimosthenis
    Palli, Domenico
    Berrino, Franco
    Vineis, Paolo
    Tumino, Rosario
    Mattiello, Amalia
    Peeters, Petra H M
    Parr, Christine L
    Gram, Inger T
    Skeie, Guri
    Sánchez, Maria-Jose
    Larrañaga, Nerea
    Ardanaz, Eva
    Navarro, Carmen
    Rodríguez, Laudina
    Ulmert, David
    Ehrnström, Roy
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Roddam, Andrew Wilfred
    Bingham, Sheila A
    Khaw, Kay-Tee
    Slimani, Nadia
    Boffetta, Paolo A
    Jenab, Mazda
    Mouw, Traci
    Michaud, Dominique S
    Riboli, Elio
    Red meat, dietary nitrosamines, and heme iron and risk of bladder cancer in the European prospective investigation into cancer and nutrition (EPIC)2011In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 20, no 3, p. 555-559Article in journal (Refereed)
    Abstract [en]

    Our findings do not support an effect of red meat intake, nitrosamines (endogenous or exogenous), or heme iron intake on bladder cancer risk. Cancer Epidemiol Biomarkers Prev; 20(3); 555-9. ©2011 AACR.

  • 202. Jankovic, N.
    et al.
    Geelen, A.
    Kampman, E.
    de Groot, C. P.
    Pikhart, H.
    Huangfu, P.
    Bofetta, P.
    Bueno-de-Mesquita, H. B.
    Kee, F.
    O'Doherty, M.
    Franco, O. H.
    Hooven van den, E. H.
    Rooij van, F.
    Trichopoulou, A.
    Orfanos, P.
    Tjonneland, A.
    Gonzalez, C. A.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Peeters, P. H.
    Park, Y.
    Pajak, A.
    Malyutina, S.
    Kubinova, R.
    Feskens, E. J.
    ASSOCIATION BETWEEN A HEALTHY DIET ACCORDING TO WHO GUIDELINES AND ALL-CAUSE MORTALITY IN EUROPEAN AND AMERICAN ELDERLY, THE CHANCES PROJECT2013In: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 63, no Supplement 1, p. 234-234Article in journal (Other academic)
    Abstract [en]

    Background and objectives: The Healthy Diet Indicator(HDI) measures adherence to the WHO guidelines for preventingdiet related chronic diseases, and can be applied to assessassociations of diet with health across populations. We examinedthe association between the HDI and all-cause mortalityin European and American elderly people aged 60 years andabove.Methods: We analysed data on 395,863 men and womenfrom 11 prospective cohort studies from the Consortium onHealth and Ageing: Network of Cohorts In Europe And TheUnited States (CHANCES). Across cohorts, the follow-upperiods ranged from 10 to 20 yrs. Diet was assessed throughvalidated methods. For the translation of foods to nutrients,country specific food composition tables were used. The continuouslyscored HDI (range mean and SD HDI score 45±9to 54±7 across cohorts) was based on intakes of saturated andpolyunsaturated fatty acids, mono-and disaccharides, protein,cholesterol, dietary fibre and fruits and vegetables. The associationbetween the HDI and all-cause mortality was evaluated ineach cohort separately, by multiple Cox proportional hazardsregression. A pooled hazard ratio (HR) was subsequently estimatedusing a random-effects model.Results: Across all cohorts, 84,863 people died during4,492,298 person-years of follow-up. Adjusted HR of death, fora 10 point increment in HDI score, ranged between 0.81 (95%CI 0.77-0.86) in Denmark and 0.99 (95% CI, 0.84-1.16) in Poland.The pooled adjusted HR estimate showed a significantinverse association of 0.90 (95% CI 0.87-0.93) but there was asignificant heterogeneity between studies (p=0.001, I2=66%).Conclusion: Our results show that higher dietary quality isinversely associated with all- cause mortality but

  • 203. Jankovic, Nicole
    et al.
    Geelen, Anouk
    Streppel, Martinette T
    de Groot, Lisette C P G M
    Orfanos, Philippos
    van den Hooven, Edith H
    Pikhart, Hynek
    Boffetta, Paolo
    Trichopoulou, Antonia
    Bobak, Martin
    Bueno-de-Mesquita, H B
    Kee, Frank
    Franco, Oscar H
    Park, Yikyung
    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.
    Tjønneland, Anne
    May, Anne M
    Pajak, Andrzej
    Malyutina, Sofia
    Kubinova, Růžena
    Amiano, Pilar
    Kampman, Ellen
    Feskens, Edith J
    Adherence to a healthy diet according to the world health organization guidelines and all-cause mortality in elderly adults from Europe and the United States2014In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 180, no 10, p. 978-988Article in journal (Refereed)
    Abstract [en]

    The World Health Organization (WHO) has formulated guidelines for a healthy diet to prevent chronic diseases and postpone death worldwide. Our objective was to investigate the association between the WHO guidelines, measured using the Healthy Diet Indicator (HDI), and all-cause mortality in elderly men and women from Europe and the United States. We analyzed data from 396,391 participants (42% women) in 11 prospective cohort studies who were 60 years of age or older at enrollment (in 1988-2005). HDI scores were based on 6 nutrients and 1 food group and ranged from 0 (least healthy diet) to 70 (healthiest diet). Adjusted cohort-specific hazard ratios were derived by using Cox proportional hazards regression and subsequently pooled using random-effects meta-analysis. During 4,497,957 person-years of follow-up, 84,978 deaths occurred. Median HDI scores ranged from 40 to 54 points across cohorts. For a 10-point increase in HDI score (representing adherence to an additional WHO guideline), the pooled adjusted hazard ratios were 0.90 (95% confidence interval (CI): 0.87, 0.93) for men and women combined, 0.89 (95% CI: 0.85, 0.92) for men, and 0.90 (95% CI: 0.85, 0.95) for women. These estimates translate to an increased life expectancy of 2 years at the age of 60 years. Greater adherence to the WHO guidelines is associated with greater longevity in elderly men and women in Europe and the United States.

  • 204. Jankovic, Nicole
    et al.
    Geelen, Anouk
    Winkels, Renate M
    Mwungura, Blaise
    Fedirko, Veronika
    Jenab, Mazda
    Illner, Anne K
    Brenner, Hermann
    Ordonez-Mena, Jose M
    Kiefte-de Jong, Jessica C
    Franco, Oscar H
    Orfanos, Philippos
    Trichopoulou, Antonia
    Boffetta, Paolo
    Agudo, Antonio
    Peeters, Petra H
    Tjonneland, Anne
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Bueno-de-Mesquita, H Bas
    Park, Yikyung
    Feskens, Edith J
    de Groot, Lisette C
    Kampman, Ellen
    Adherence to the WCRF/AICR Dietary Recommendations for Cancer Prevention and Risk of Cancer in Elderly from Europe and the United States: A Meta-Analysis within the CHANCES Project2017In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 26, no 1, p. 136-144Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: It is unknown if dietary recommendations for cancer prevention are applicable to the elderly. We analyzed WCRF/AICR recommendations in cohorts of European and US adults aged 60 years and above.

    METHODS: Individual participant data meta-analysis including 362,114 participants (43% women), from seven prospective cohort studies, free from cancer at enrollment. The WCRF/AICR diet score was based on: 1) energy-dense foods and sugary drinks, 2) plant foods, 3) red and processed meat 4) alcoholic drinks. Cox proportional hazards regression was used to examine the association between the diet score and cancer risks. Adjusted, cohort-specific hazard ratios (HR) were pooled using random-effects meta-analysis. Risk Advancement Periods (RAP) were calculated to quantify the time period by which the risk of cancer was postponed among those adhering to the recommendations.

    RESULTS: After a median follow-up of 11 to 15 years across cohorts, 69,708 cancer cases were identified. Each one-point increase in the WCRF/AICR diet score [range 0 (no) to 4 (complete adherence)] was significantly associated with a lower risk of total cancer (HR: 0.94, 95% CI: 0.92-0.97), cancers of the colorectum (HR: 0.84, 95% CI: 0.80-0.89), prostate (HR: 0.94, 95% CI: 0.92-0.97), but not breast or lung. Adherence to an additional component of the WCRF/AICR diet score significantly postponed the incidence of cancer at any site by 1.6 years (RAP: -1.6, 95% CI: -4.09 to -2.16).

    CONCLUSION: Adherence to WCRF/AICR dietary recommendations is associated with lower risk of cancer among older adults.

    IMPACT: Dietary recommendations for cancer prevention are applicable to the elderly.

  • 205. Jenab, Mazda
    et al.
    Bueno-de-Mesquita, H Bas
    Ferrari, Pietro
    van Duijnhoven, Franzel J B
    Norat, Teresa
    Pischon, Tobias
    Jansen, Eugène H J M
    Slimani, Nadia
    Byrnes, Graham
    Rinaldi, Sabina
    Tjønneland, Anne
    Olsen, Anja
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Françoise
    Morois, Sophie
    Kaaks, Rudolf
    Linseisen, Jakob
    Boeing, Heiner
    Bergmann, Manuela M
    Trichopoulou, Antonia
    Misirli, Gesthimani
    Trichopoulos, Dimitrios
    Berrino, Franco
    Vineis, Paolo
    Panico, Salvatore
    Palli, Domenico
    Tumino, Rosario
    Ros, Martine M
    van Gils, Carla H
    Peeters, Petra H
    Brustad, Magritt
    Lund, Eiliv
    Tormo, María-José
    Ardanaz, Eva
    Rodríguez, Laudina
    Sánchez, Maria-José
    Dorronsoro, Miren
    Gonzalez, Carlos A
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Roddam, Andrew
    Key, Timothy J
    Khaw, Kay-Tee
    Autier, Philippe
    Hainaut, Pierre
    Riboli, Elio
    Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations: a nested case-control study2010In: BMJ. British Medical Journal (International Ed.), ISSN 0959-8146, E-ISSN 0959-535X, Vol. 340, p. b5500-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine the association between pre-diagnostic circulating vitamin D concentration, dietary intake of vitamin D and calcium, and the risk of colorectal cancer in European populations. DESIGN: Nested case-control study. Setting The study was conducted within the EPIC study, a cohort of more than 520 000 participants from 10 western European countries. PARTICIPANTS: 1248 cases of incident colorectal cancer, which developed after enrolment into the cohort, were matched to 1248 controls MAIN OUTCOME MEASURES: Circulating vitamin D concentration (25-hydroxy-vitamin-D, 25-(OH)D) was measured by enzyme immunoassay. Dietary and lifestyle data were obtained from questionnaires. Incidence rate ratios and 95% confidence intervals for the risk of colorectal cancer by 25-(OH)D concentration and levels of dietary calcium and vitamin D intake were estimated from multivariate conditional logistic regression models, with adjustment for potential dietary and other confounders. RESULTS: 25-(OH)D concentration showed a strong inverse linear dose-response association with risk of colorectal cancer (P for trend <0.001). Compared with a pre-defined mid-level concentration of 25-(OH)D (50.0-75.0 nmol/l), lower levels were associated with higher colorectal cancer risk (<25.0 nmol/l: incidence rate ratio 1.32 (95% confidence interval 0.87 to 2.01); 25.0-49.9 nmol/l: 1.28 (1.05 to 1.56), and higher concentrations associated with lower risk (75.0-99.9 nmol/l: 0.88 (0.68 to 1.13); >or=100.0 nmol/l: 0.77 (0.56 to 1.06)). In analyses by quintile of 25-(OH)D concentration, patients in the highest quintile had a 40% lower risk of colorectal cancer than did those in the lowest quintile (P<0.001). Subgroup analyses showed a strong association for colon but not rectal cancer (P for heterogeneity=0.048). Greater dietary intake of calcium was associated with a lower colorectal cancer risk. Dietary vitamin D was not associated with disease risk. Findings did not vary by sex and were not altered by corrections for season or month of blood donation. CONCLUSIONS: The results of this large observational study indicate a strong inverse association between levels of pre-diagnostic 25-(OH)D concentration and risk of colorectal cancer in western European populations. Further randomised trials are needed to assess whether increases in circulating 25-(OH)D concentration can effectively decrease the risk of colorectal cancer.

  • 206. Jenab, Mazda
    et al.
    McKay, James
    Bueno-de-Mesquita, Hendrik B
    van Duijnhoven, Franzel J B
    Ferrari, Pietro
    Slimani, Nadia
    Jansen, Eugène H J M
    Pischon, Tobias
    Rinaldi, Sabina
    Tjønneland, Anne
    Olsen, Anja
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Françoise
    Engel, Pierre
    Kaaks, Rudolf
    Linseisen, Jakob
    Boeing, Heiner
    Fisher, Eva
    Trichopoulou, Antonia
    Dilis, Vardis
    Oustoglou, Erifili
    Berrino, Franco
    Vineis, Paolo
    Mattiello, Amalia
    Masala, Giovanna
    Tumino, Rosario
    Vrieling, Alina
    van Gils, Carla H
    Peeters, Petra H
    Brustad, Magritt
    Lund, Eiliv
    Chirlaque, María-Dolores
    Barricarte, Aurelio
    Suárez, Laudina Rodríguez
    Molina, Esther
    Dorronsoro, Miren
    Sala, Núria
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Roddam, Andrew
    Key, Timothy J
    Khaw, Kay-Tee
    Bingham, Sheila
    Boffetta, Paolo
    Autier, Philippe
    Byrnes, Graham
    Norat, Teresa
    Riboli, Elio
    Vitamin D receptor and Calcium sensing receptor Polymorphisms and the risk of Colorectal Cancer in European populations2009In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 18, p. 2485-2491Article in journal (Refereed)
    Abstract [en]

    Increased levels of vitamin D and calcium may play a protective role in colorectal cancer (CRC) risk. It has been suggested that these effects may be mediated by genetic variants of the vitamin D receptor (VDR) and the calcium sensing receptor (CASR). However, current epidemiologic evidence from European populations for a role of these genes in CRC risk is scarce. In addition, it is not clear whether these genes may modulate CRC risk independently or by interaction with blood vitamin D concentration and level of dietary calcium intake. A case-control study was conducted nested within the European Prospective Investigation into Cancer and Nutrition. CRC cases (1,248) were identified and matched to 1,248 control subjects. Genotyping for the VDR (BsmI: rs1544410; Fok1: rs2228570) and CASR (rs1801725) genes was done by Taqman, and serum vitamin D (25OHD) concentrations were measured. Conditional logistic regression was used to estimate the incidence rate ratio (RR). Compared with the wild-type bb, the BB genotype of the VDR BsmI polymorphism was associated with a reduced risk of CRC [RR, 0.76; 95% confidence interval (CI), 0.59-0.98). The association was observed for colon cancer (RR, 0.69; 95% CI, 0.45-0.95) but not rectal cancer (RR, 0.97; 95% CI, 0.62-1.49). The Fok1 and CASR genotypes were not associated with CRC risk in this study. No interactions were noted for any of the polymorphisms with serum 25OHD concentration or level of dietary calcium. These results confirm a role for the BsmI polymorphism of the VDR gene in CRC risk, independent of serum 25OHD concentration and dietary calcium intake. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2485-91).

  • 207. Jenab, Mazda
    et al.
    McKay, James D
    Ferrari, Pietro
    Biessy, Carine
    Laing, Stewart
    Munar, Gabriel Maria Capella
    Sala, Núria
    Peña, Salvador
    Crusius, J B A
    Overvad, Kim
    Jensen, Majken K
    Olsen, Anja
    Tjonneland, Anne
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Kaaks, Rudolf
    Linseisen, Jakob
    Boeing, Heiner
    Bergmann, Manuela M
    Trichopoulou, Antonia
    Georgila, Christina
    Psaltopoulou, Theodora
    Mattiello, Amalia
    Vineis, Paolo
    Pala, Valeria
    Palli, Domenico
    Tumino, Rosario
    Numans, Mattijs E
    Peeters, Petra H M
    Bueno-de-Mesquita, H Bas
    Lund, Eiliv
    Ardanaz, Eva
    Sánchez, Maria-Jose
    Dorronsoro, Miren
    Sanchez, Carmen Navarro
    Quirós, José Ramón
    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.
    Manjer, Jonas
    Régner, Sara
    Key, Tim
    Bingham, Sheila
    Khaw, Kay-tee
    Slimani, Nadia
    Rinaldi, Sabina
    Boffetta, Paolo
    Carneiro, Fátima
    Riboli, Elio
    Gonzalez, Carlos
    CDH1 gene polymorphisms, smoking, Helicobacter pylori infection and the risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST).2008In: Eur J Cancer, ISSN 0959-8049, Vol. 44, no 6, p. 774-780Article in journal (Refereed)
  • 208. Jenab, Mazda
    et al.
    Riboli, Elio
    Cleveland, Rebecca J
    Norat, Teresa
    Rinaldi, Sabina
    Nieters, Alexandra
    Biessy, Carine
    Tjønneland, Ann
    Olsen, Anja
    Overvad, Kim
    Grønbaek, Henning
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Linseisen, Jakob
    Boeing, Heiner
    Pischon, Tobias
    Trichopoulos, Dimitrios
    Oikonomou, Eleni
    Trichopoulou, Antonia
    Panico, Salvatore
    Vineis, Paolo
    Berrino, Franco
    Tumino, Rosario
    Masala, Giovanna
    Peters, Petra H
    van Gils, Carla H
    Bueno-de-Mesquita, H Bas
    Ocké, Marga C
    Lund, Eiliv
    Mendez, Michelle A
    Tormo, María José
    Barricarte, Aurelio
    Martínez-García, Carmen
    Dorronsoro, Miren
    Quirós, José Ramón
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Patologi.
    Berglund, Göran
    Manjer, Jonas
    Key, Timothy
    Allen, Naomi E
    Bingham, Sheila
    Khaw, Kay-Tee
    Cust, Anne
    Kaaks, Rudolf
    Serum C-peptide, IGFBP-1 and IGFBP-2 and risk of colon and rectal cancers in the European Prospective Investigation into Cancer and Nutrition.2007In: International Journal of Cancer, ISSN 0020-7136, Vol. 121, no 2, p. 368-76Article in journal (Refereed)
  • 209. Jenab, Mazda
    et al.
    Riboli, Elio
    Ferrari, Pietro
    Sabate, Joan
    Slimani, Nadia
    Norat, Teresa
    Friesen, Marlin
    Tjänneland, Anne
    Olsen, Anja
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Francois
    Touvier, Mathilde
    Boeing, Heiner
    Schulz, Mandy
    Linseisen, Jakob
    Nagel, Gabriele
    Trichopoulou, Antonia
    Naska, Androniki
    Oikonomou, Eleni
    Krogh, Vittorio
    Panico, Salvatore
    Masala, Giovanna
    Sacerdote, Carlotta
    Tumino, Rosario
    Peeters, Petra H
    Numans, Mattijs E
    Bueno-de-Mesquita, Hendrik B
    Büchner, Frederike L
    Lund, Eiliv
    Pera, Guillem
    Sanchez, Carmen Navarro
    Sanchez, Maria-Jose
    Arriola, Larraitz
    Barricarte, Aurelio
    Quiros, José R
    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. Patologi.
    Berglund, Göran
    Bingham, Sheila
    Khaw, Kay-Tee
    Key, Timothy
    Allen, Naomi
    Carneiro, Fatima
    Mahlke, U
    Del Giudice, Guiseppe
    Palli, Domenico
    Kaaks, Rudolf
    Gonzalez, Carlos A
    Plasma and dietary vitamin C levels and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST).2006In: Carcinogenesis, ISSN 0143-3334, Vol. 27, no 11, p. 2250-7Article in journal (Refereed)
  • 210. Jeurnink, SM
    et al.
    Büchner, FL
    Bueno-de-Mesquita, HB
    Siersema, PD
    Boshuizen, HC
    Numans, ME
    Dahm, CC
    Overvad, K
    Tjønneland, A
    Roswall, N
    Clavel-Chapelon, F
    Boutron-Ruault, MC
    Morois, S
    Kaaks, R
    Teucher, B
    Boeing, H
    Buijsse, B
    Trichopoulou, A
    Benetou, V
    Zylis, D
    Palli, D
    Sieri, S
    Vineis, P
    Tumino, R
    Panico, S
    Ocké, MC
    Peeters, PHM
    Skeie, G
    Brustad, M
    Lund, E
    Sánchez-Cantalejo, E
    Navarro, C
    Amiano, P
    Ardanaz, E
    Quirós, J Ramón
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, I
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lindkvist, B
    Regnér, S
    Khaw, KT
    Wareham, N
    Key, TJ
    Slimani, N
    Norat, T
    Vergnaud, AC
    Romaguera, D
    Gonzalez, CA
    Variety in vegetable and fruit consumption and the risk of gastric and esophageal cancer in the European Prospective investigation into cancer and nutrition2012In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 131, no 6, p. E963-E973Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Diets high in vegetables and fruits have been suggested to be inversely associated with risk of gastric cancer. However, the evidence of the effect of variety of consumption is limited. We therefore investigated whether consumption of a variety of vegetables and fruit is associated with gastric and esophageal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

    METHODS: Data on food consumption and follow-up on cancer incidence was available for 452,269 participants from 10 European countries. After a mean follow-up of 8.4 years, 475 cases of gastric and esophageal adenocarcinomas (180 non-cardia, 185 cardia, gastric esophageal junction and esophagus, 110 not specified) and 98 esophageal squamous cell carcinomas were observed. Diet Diversity Scores (DDSs) were used to quantify the variety in vegetable and fruit consumption. We used multivariable Cox proportional hazard models to calculate risk ratios.

    RESULTS: Independent from quantity of consumption, variety in the consumption of vegetables and fruit combined and of fruit consumption alone were statistically significantly inversely associated with the risk of esophageal squamous cell carcinoma (continuous HR per 2 products increment 0.88; 95%CI 0.79-0.97 and 0.76; 95%CI 0.62-0.94, respectively) with the latter particularly seen in ever smokers. Variety in vegetable and/or fruit consumption was not associated with risk of gastric and esophageal adenocarcinomas.

    CONCLUSION: Independent from quantity of consumption, more variety in vegetable and fruit consumption combined and in fruit consumption alone may decrease the risk of esophageal squamous cell carcinoma. However, residual confounding by lifestyle factors can not be excluded. © 2012 Wiley-Liss, Inc.

  • 211. Jin, Qianren
    et al.
    Hemminki, Kari
    Enquist, Kerstin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Onkologi.
    Grzybowska, Ewa
    Klaes, Rüdinger
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Onkologi.
    Chen, Bowang
    Pamula, Jolanta
    Pekala, Wioletta
    Zientek, Helena
    Rogozinska-Szczepka, Jadwiga
    Utracka-Hutka, Beata
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Försti, Asta
    Vascular endothelial growth factor polymorphisms in relation to breast cancer development and prognosis2005In: Clinical Cancer Research, ISSN 1078-0432, Vol. 11, no 10, p. 3647-3653Article in journal (Refereed)
  • 212. Johansen, Dorthe
    et al.
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lindkvist, Björn
    Björge, Tone
    Concin, Hans
    Almquist, Martin
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Engeland, Anders
    Ulmer, Hanno
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Selmer, Randi
    Nagel, Gabriele
    Tretli, Steinar
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Manjer, Jonas
    Metabolic factors and the risk of pancreatic cancer: a prospective analysis of almost 580,000 men and women in the Metabolic Syndrome and Cancer Project2010In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 19, no 9, p. 2307-2317Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim of this study was to investigate the association between factors in metabolic syndrome (MetS; single and combined) and the risk of pancreatic cancer. METHODS: The Metabolic Syndrome and Cancer Project is a pooled cohort containing data on body mass index, blood pressure, and blood levels of glucose, cholesterol, and triglycerides. During follow-up, 862 individuals were diagnosed with pancreatic cancer. Cox proportional hazards analysis was used to calculate relative risks (RR) with 95% confidence intervals using the above-mentioned factors categorized into quintiles and transformed into z-scores. All z-scores were summarized and a second z-transformation creating a composite z-score for MetS was done. All risk estimates were calibrated to correct for a regression dilution bias. RESULTS: The trend over quintiles was positively associated with the risk of pancreatic cancer for mid-blood pressure (mid-BP) and glucose in men and for body mass index, mid-BP, and glucose in women. The z-score for the adjusted mid-BP (RR, 1.10; 1.01-1.20) and the calibrated z-score for glucose (RR, 1.37; 1.14-1.34) were positively associated with pancreatic cancer in men. In women, a positive association was found for calibrated z-scores for mid-BP (RR, 1.34; 1.08-1.66), for the calibrated z-score for glucose (RR, 1.98; 1.41-2.76), and for the composite z-score for MetS (RR, 1.58; 1.34-1.87). CONCLUSION: Our study adds further evidence to a possible link between abnormal glucose metabolism and risk of pancreatic cancer. IMPACT: To our knowledge, this is the first study on MetS and pancreatic cancer using prediagnostic measurements of the examined factors.

  • 213.
    Johansson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Molecular Periodontology.
    Eriksson, Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Åhren, Ann-Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Boman, Kurt
    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.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Prevalence of systemic immunoreactivity to Aggregatibacter actinomycetemcomitans leukotoxin in relation to the incidence of myocardial infarction2011In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 11, no 1, p. 55-Article in journal (Refereed)
    Abstract [en]

    Background: Chronic infections and associated inflammatory markers are suggested risk factors for cardiovascular disease (CVD). The proinflammatory cytokine, interleukin (IL)-1, is suggested to play a role in the regulation of local inflammatory responses in both CVD and periodontitis. The leukotoxin from the periodontal pathogen Aggregatibacter actinomycetemcomitans has recently been shown to cause abundant secretion of IL-1 from macrophages. The aim of the present study was to compare the prevalence of systemic immunoreactivity to A. actinomycetemcomitans leukotoxin in myocardial infarction (MI) cases (n=532) and matched controls (n=1000) in a population-based case and referents study in northern Sweden.

    Methods: Capacity to neutralize A. actinomycetemcomitans leukotoxin was analyzed in a bioassay with leukocytes, purified leukotoxin, and plasma. Plasma samples that inhibited lactate-dehydrogenase release from leukotoxin-lysed cells by 50 % were classified as positive.

    Results: Neutralizing capacity against A. actinomycetemcomitans leukotoxin was detected in 53.3% of the plasma samples. The ability to neutralize leukotoxin correlated to increasing age in men (n=1082) but not in women (n=450). There was no correlation between presence of systemic leukotoxin neutralization capacity and the incidence of MI, except for women (n=146). Women with a low neutralizing capacity had a significantly higher incidence of MI than those who had a high neutralizing capacity.

    Conclusions: Systemic immunoreactivity against A. actinomycetemcomitans leukotoxin was found at a high prevalence in the analyzed population of adults from northern Sweden. The results from the present study do not support the hypothesis that systemic leukotoxin-neutralizing capacity can decrease the risk for MI.

  • 214.
    Johansson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Eriksson, Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Åhrén, Ann-Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Systemic antibodies to the leukotoxin of the oral pathogen Actinobacillus actinomycetemcomitans correlate negatively with stroke in women2005In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 20, no 4, p. 226-232Article in journal (Refereed)
    Abstract [en]

    Background: Chronic infections and associated inflammatory markers are suggested risk factors for cardiovascular diseases (CVD) and stroke. The proinflammatory cytokine interleukin (IL)-1β is suggested to play a role in the regulation of local inflammatory responses in both CVD and periodontitis. The leukotoxin from the periodontal pathogen Actinobacillus actinomycetemcomitans has recently been shown to cause abundant secretion of IL-1β  from macrophages. The aim of the present study was to compare the prevalence of systemic antibodies to A. actinomycetemcomitansleukotoxin in stroke cases (n = 273) and matched controls (n = 546) in an incident case-control study nested within the Northern Sweden MONICA and Västerbotten Intervention cohorts.

    Methods: Antibodies to A. actinomycetemcomitans leukotoxin were analyzed in a bioassay with HL-60 cells (leukocytes), purified A. actinomycetemcomitans leukotoxin, and plasma. Plasma samples which inhibited lactate dehydrogenase release from leukotoxin-lysed cells by ≥50% were classified as antibody positive.

    Results: Antibodies to A. actinomycetemcomitans leukotoxin were detected in 18.8% of the women and 15.2% of the men. Women with those antibodies had a significantly decreased risk for stroke (OR = 0.28, 95% CI: 0.13–0.59), but not men (OR = 0.88, 95% CI: 0.52–1.51).

    Conclusion: The immunoreactivity to A. actinomycetemcomitans leukotoxin correlates negatively with a future stroke in woman, but not in men. Further studies are needed to explain the underlying mechanisms, as well as the biological relevance of this finding.

  • 215. Johansson, G
    et al.
    Wikman, Å
    Åhrén, Ann-Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Underreporting of energy intake in repeated 24-hour recalls related to gender, age, weight status, day of interview, educational level, reported food intake, smoking habits and area of living.2001In: Public Health Nutrition, ISSN 1368-9800, E-ISSN 1475-2727, Vol. 4, no 4, p. 919-927Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aims of the present study were (1) to evaluate the degree to which underreporting of energy intake by repeated 24-hour recalls was related to gender, age, weight status, day of interview, educational level, smoking habits and area of living, and (2) to compare the dietary characteristics of underreporters with those of others. DESIGN: Cross-sectional study. Ten 24-hour recalls were performed during a one-year period. SETTING: The Västerbotten intervention programme of cardiovascular disease and diabetes in Northern Sweden. SUBJECTS: Ninety-four men and 99 women in four age groups: 30, 40, 50 and 60 years. RESULTS: The prevalence of men and women with a food intake level (FIL; reported energy intake divided by estimated basal metabolic rate) below 1.2 was 44% and 47%, respectively. The youngest age group had higher FIL values than the oldest age group for both men (1.5 versus 1.1) and women (1.4 versus 1.1). The prevalence and magnitude of underreporting were directly related to body mass index (BMI; correlation coefficient: -0.47 (men) and -0.55 (women)). Smokers had a lower FIL value (1.1) than non-smokers (1.3). The nutrient density was lower for the group with high FIL values for protein and calcium and higher for fat and sucrose. The upper FIL group often had higher intake frequencies and larger portion sizes than the lower FIL group. CONCLUSIONS: Underreporting of energy intake is prevalent when 24-hour recalls are used, but the prevalence differs between sub-groups in the population. BMI was the main predictor of underreporting but also old age and smoking seem to contribute in this aspect. Socially desirable food items were not underreported to the same extent as socially undesirable food items. The intake frequencies and portion sizes partly explained the differences in FIL.

  • 216.
    Johansson, Ingegerd
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Wikman, Å
    Biessy, C
    Riboli, E
    Kaaks, R
    Validation and calibration of food-frequency questionnaire measurements in the Northern Sweden Health and Disease cohort.2002In: Public Health Nutrition, ISSN 1368-9800, E-ISSN 1475-2727, Vol. 5, no 3, p. 487-96Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To evaluate the reproducibility of, and to compare and calibrate, diet measures by the Northern Sweden 84-item food-frequency questionnaire (FFQ) with measures from 24-hour diet recalls (24-HDR). DESIGN: Randomly selected respondents from the EPIC (diet-cancer) and MONICA (diet-cardiovascular disease) study cohort in Northern Sweden were invited to answer the FFQ twice over a one-year interval (FFQ1 and FFQ2), and to complete ten 24-hour recalls (reference method) in the months between. Plasma beta-carotene concentrations were determined from a subset of 47 participants. SETTING: Västerbotten and Norrbotten, Northern Sweden. PARTICIPANTS: Ninety-six men and 99 women, who completed the study. RESULTS: The reproducibility of the FFQ was high in terms of both mean energy and nutrient intakes and relative ranking of participants by intake levels (median Pearson correlation of 0.68). Moderately higher food intake frequencies were recorded by FFQ1 compared with 24-hour recalls for dairy products, bread/cereals, vegetables, fruits and potato/rice/pasta, whereas meat, fish, sweet snacks and alcoholic beverage intakes were lower. The median Spearman coefficient of correlation between FFQ1 and the average of ten 24-HDR measurements was 0.50. Daily energy and nutrient intakes were similar for FFQ1 and 24-HDR measurements, except for fibre, vitamin C, beta-carotene and retinol (FFQ1>24-HDR) and sucrose and cholesterol Pearson coefficients of correlation between FFQ1 and 24-HDR corrected for attenuation due to residual day-to-day variation in the 24-HDR measurements ranged from 0.36 to 0.79 (median 0.54). Adjustment for energy had only very moderate effects on the correlation estimates. Calibration coefficients estimated by linear regression of the 24-HDR on the FFQ1 measurements varied between 0.30 and 0.59 for all nutrients except alcohol, which had calibration coefficients close to 1.0. These low calibration coefficients indicate that relative risk estimates corresponding to an absolute difference in dietary intake levels measured by the FFQ will generally be biased towards 1.0. Plasma beta-carotene levels had a Pearson coefficient of correlation of 0.47 with the 24-HDR measurements, and of 0.23 with FFQ1 measurements. CONCLUSIONS: The Northern Sweden FFQ measurements have good reproducibility and an estimated level of validity similar to that of FFQ measurements in other prospective cohort studies. The results from this study will form the basis for the correction of attenuation and regression dilution biases in relative risk estimates, in future studies relating FFQ measurements to disease outcomes.

  • 217.
    Johansson, Ingegerd
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Stegmayr, Birgitta
    The National Board of Welfare, Stockholm, Sweden .
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Medicine, Skellefteå County Hospital, Skellefteå, Sweden.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Winkvist, Anna
    Associations among 25-year trends in diet, cholesterol and BMI from 140,000 observations in men and women in Northern Sweden2012In: Nutrition Journal, ISSN 1475-2891, E-ISSN 1475-2891, Vol. 11, article id 40Article in journal (Refereed)
    Abstract [en]

    Background: In the 1970s, men in northern Sweden had among the highest prevalences of cardiovascular diseases (CVD) worldwide. An intervention program combining population- and individual-oriented activities was initiated in 1985. Concurrently, collection of information on medical risk factors, lifestyle and anthropometry started. Today, these data make up one of the largest databases in the world on diet intake in a population- based sample, both in terms of sample size and follow-up period. The study examines trends in food and nutrient intake, serum cholesterol and body mass index (BMI) from 1986 to 2010 in northern Sweden.

    Methods: Cross-sectional information on self-reported food and nutrient intake and measured body weight, height, and serum cholesterol were compiled for over 140,000 observations. Trends and trend breaks over the 25-year period were evaluated for energy-providing nutrients, foods contributing to fat intake, serum cholesterol and BMI.

    Results: Reported intake of fat exhibited two significant trend breaks in both sexes: a decrease between 1986 and 1992 and an increase from 2002 (women) or 2004 (men). A reverse trend was noted for carbohydrates, whereas protein intake remained unchanged during the 25-year period. Significant trend breaks in intake of foods contributing to total fat intake were seen. Reported intake of wine increased sharply for both sexes (more so for women) and export beer increased for men. BMI increased continuously for both sexes, whereas serum cholesterol levels decreased during 1986 - 2004, remained unchanged until 2007 and then began to rise. The increase in serum cholesterol coincided with the increase in fat intake, especially with intake of saturated fat and fats for spreading on bread and cooking.

    Conclusions: Men and women in northern Sweden decreased their reported fat intake in the first 7 years (19861992) of an intervention program. After 2004 fat intake increased sharply for both genders, which coincided with introduction of a positive media support for low carbohydrate-high-fat (LCHF) diet. The decrease and following increase in cholesterol levels occurred simultaneously with the time trends in food selection, whereas a constant increase in BMI remained unaltered. These changes in risk factors may have important effects on primary and secondary prevention of cardiovascular disease (CVD).

  • 218.
    Johansson, Ingegerd
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Tidehag, P
    Lundberg, V
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Dental status, diet and cardiovascular risk factors in middle-aged people in northern Sweden.1994In: Community Dentistry and Oral Epidemiology, ISSN 0301-5661, E-ISSN 1600-0528, Vol. 22, no 6, p. 431-436Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to compare the dietary intake and the levels of traditional cardiovascular (CVD) risk factors in edentulous middle-aged individuals and individuals of the same age and sex who still had natural teeth. The study was performed within the framework of the MONICA-project. Population registers were used to sample randomly 1287 men and 1330 women aged 25-64 yr. Data were collected from a mailed questionnaire, blood analyses, registrations of blood pressure and anthropometric measures. The estimated daily energy intake did not differ between the two groups, but edentulous men and women ate more sweet snacks compared to those who still had teeth. Edentulous men also ate less fruits, vegetables and fibre and edentulous women ate more fat than dentates. Edentulous men and women were more obese and had lower serum HDL-cholesterol concentrations than those with remaining teeth. Edentulous women also had significantly higher concentrations of total cholesterol and triglycerides in serum than dentate women. Edentulous men and women were more often regular smokers, but not snuff users, than dentates of the same age and sex. Thus, the presence of two or more cardiovascular risk factors was more common in edentulous individuals than in those who still had natural teeth. In summary, these results support the hypothesis that edentulous middle-aged individuals have a more unfavourable risk factor profile for CVD. Counselling on balanced dietary habits and non-smoking given by dental personnel to orally diseased patients--recommendations given to improve resistance to dental caries or periodontitis--might therefore improve general health and possibly also improve risk factors for CVD.

  • 219.
    Johansson, Ingegerd
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Johansson, M
    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.
    Validity of food frequency questionnaire estimated intakes of folate and other B vitamins in a region without folic acid fortification.2010In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 64, no 8, p. 905-913Article in journal (Refereed)
    Abstract [en]

    Background/Objectives: 

    B vitamins have been implicated in major chronic diseases but results have been inconsistent. This study evaluated the accuracy of dietary intakes of folate, vitamin B12, riboflavin and vitamin B6 as measured by the Northern Sweden Food Frequency Questionnaire (FFQ) against repeated 24-h recalls (24HR) and plasma levels, taking into consideration the MTHFR 677C>T polymorphism.

    Subjects/Methods: 

    B vitamin intakes assessed by a semi-quantitative FFQ designed to measure the intake over the previous year were compared with those from 10 24HR, as well as to plasma levels of folate and vitamin B12, in randomly selected men (n=96) and women (n=99) aged 30–60 years. FFQ-based B-vitamin intakes were also compared with plasma levels of B-vitamins and with MTHFR 677C4T genotype in 878 men, aged 40–61 years.

    Results: 

    Intakes of vitamins B12 and riboflavin were similar, whereas folate and B6 intakes were 16–27% higher, as estimated by FFQ versus 24HR. Spearman correlation coefficients between the two methods ranged from 0.31 to 0.63 (all P0.002), and were lowest for vitamin B12. Intakes estimated by FFQ were correlated with plasma levels, but coefficients were lower (range: 0.13–0.33), particularly for vitamin B12 in men (0.15–0.18). Folate intake was not correlated with plasma levels in subjects with the MTHFR 677 T/T genotype.

    Conclusions: 

    The validity of the Northern Sweden FFQ for assessing B vitamin intake is similar to that of many other FFQs used in large-scale studies. The FFQ is suitable for ranking individuals by intake of folate, riboflavin, vitamin B6 and to a lesser extent vitamin B12.

  • 220.
    Johansson, Lars
    et al.
    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.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Torbjörn K
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hemostatic factors as risk markers for intracerebral hemorrhage: a prospective incident case-referent study.2004In: Stroke, ISSN 1524-4628, Vol. 35, no 4, p. 826-30Article in journal (Refereed)
  • 221.
    Johansson, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology. Reumatologi.
    Ärlestig, Lisbeth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology. Reumatologi.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology. Reumatologi.
    PTPN22 polymorphism and anti-cyclic citrullinated peptide antibodies in combination strongly predicts future onset of rheumatoid arthritis and has a specificity of 100% for the disease2006In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 8, no 1, p. R19-Article in journal (Refereed)
  • 222.
    Johansson, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Appleby, Paul N
    Allen, Naomi E
    Travis, Ruth C
    Roddam, Andrew W
    Egevad, Lars
    Jenab, Mazda
    Rinaldi, Sabina
    Kiemeney, Lambertus A
    Bueno-de-Mesquita, H Bas
    Vollset, Stein Emil
    Ueland, Per M
    Sánchez, Maria-José
    Quirós, J Ramón
    González, Carlos A
    Larrañaga, Nerea
    Chirlaque, María Dolores
    Ardanaz, Eva
    Sieri, Sabina
    Palli, Domenico
    Vineis, Paolo
    Tumino, Rosario
    Linseisen, Jakob
    Kaaks, Rudolf
    Boeing, Heiner
    Pischon, Tobias
    Psaltopoulou, Theodora
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Khaw, Kay-Tee
    Bingham, Sheila
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Riboli, Elio
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Urologi och andrologi.
    Key, Timothy J
    Circulating concentrations of folate and vitamin B12 in relation to prostate cancer risk: results from the European prospective investigation into cancer and nutrition study2008In: Cancer Epidemiol Biomarkers Prev, ISSN 1055-9965, Vol. 17, no 2, p. 279-285Article in journal (Refereed)
    Abstract [en]

    Background: Determinants of one-carbon metabolism, such as folate and vitamin B12, have been implicated in cancer development. Previous studies have not provided conclusive evidence for the importance of circulating concentrations of folate and vitamin B12 in prostate cancer etiology. The aim of the present study was to investigate the relationship between prostate cancer risk and circulating concentrations of folate and vitamin B12 in a large prospective cohort. Methods: We analyzed circulating concentrations of folate and vitamin B12 in 869 cases and 1,174 controls, individually matched on center, age, and date of recruitment, nested within the European Prospective Investigation into Cancer and Nutrition cohort. Relative risks (RR) for prostate cancer were estimated using conditional logistic regression models. Results: Overall, no significant associations were observed for circulating concentrations of folate (Ptrend = 0.62) or vitamin B12 (Ptrend = 0.21) with prostate cancer risk. RRs for a doubling in folate and vitamin B12 concentrations were 1.03 [95% confidence interval (95% CI), 0.92-1.16] and 1.12 (95% CI, 0.94-1.35), respectively. In the subgroup of cases diagnosed with advanced stage prostate cancer, elevated concentrations of vitamin B12 were associated with increased risk (RR for a doubling in concentration, 1.69; 95% CI, 1.05-2.72, Ptrend = 0.03). No other subgroup analyses resulted in a statistically significant association. Conclusion: This study does not provide strong support for an association between prostate cancer risk and circulating concentrations of folate or vitamin B12. Elevated concentrations of vitamin B12 may be associated with an increased risk for advanced stage prostate cancer, but this association requires examination in other large prospective studies. (Cancer Epidemiol Biomarkers Prev 2007;17(2):279–85)

  • 223.
    Johansson, Mattias
    et al.
    International Agency for Research on Cancer, Lyon, France.
    Fanidi, Anouar
    Muller, David C.
    Bassett, Julie K.
    Midttun, Oivind
    Vollset, Stein Emil
    Travis, Ruth C.
    Palli, Domenico
    Mattiello, Amalia
    Sieri, Sabina
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    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.
    Weiderpass, Elisabete
    Skeie, Guri
    Gonzalez, Carlos A.
    Dorronsoro, Miren
    Peeters, Petra H.
    Bueno-de-Mesquita, H. B(as).
    Ros, Martine M.
    Ruault, Marie-Christine Boutron
    Fagherazzi, Guy
    Clavel, Francoise
    Sanchez, Maria-Jose
    Barricarte Gurrea, Aurelio
    Navarro, Carmen
    Ramon Quiros, J.
    Overvad, Kim
    Tjonneland, Anne
    Aleksandrova, Krassimira
    Vineis, Paolo
    Gunter, Marc J.
    Kaaks, Rudolf
    Giles, Graham
    Relton, Caroline
    Riboli, Elio
    Boeing, Heiner
    Ueland, Per Magne
    Severi, Gianluca
    Brennan, Paul
    Circulating Biomarkers of One-Carbon Metabolism in Relation to Renal Cell Carcinoma Incidence and Survival2014In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 106, no 12, article id dju327Article in journal (Refereed)
    Abstract [en]

    Background: The etiology of renal cell carcinoma (RCC) is only partially understood, but a metabolic component appears likely. We investigated biomarkers of one-carbon metabolism and RCC onset and survival. Methods: The European Prospective Investigation into Cancer and Nutrition (EPIC) recruited 385 747 participants with blood samples between 1992 and 2000, and this analysis included 556 RCC case-control pairs. A subsequent replication study included 144 case-control pairs nested within the Melbourne Collaborative Cohort Study (MCCS). Plasma concentrations of vitamin B2, vitamin B6, folate, vitamin B12, methionine and homocysteine were measured in prediagnostic samples and evaluated with respect to RCC risk using conditional and unconditional logistic regression models, and to all-cause mortality in RCC cases using Cox regression models. All statistical tests were two-sided. Results: EPIC participants with higher plasma concentrations of vitamin B6 had lower risk of RCC, the odds ratio comparing the 4th and 1st quartiles (OR4vs1) being 0.40 95% confidence interval [CI] = 0.28 to 0.57, P-trend < .001. We found similar results after adjusting for potential confounders (adjusted P-trend < .001). In survival analysis, the hazard ratio for all-cause mortality in RCC cases when comparing the 4th and 1st quartiles (HR4vs1) of vitamin B6 was 0.57 (95% CI = 0.37 to 0.87, P-trend < .001). Subsequent replication of these associations within the MCCS yielded very similar results for both RCC risk (OR4vs1 = 0.47, 95% CI = 0.23 to 0.99, P-trend = .07) and all-cause mortality (HR4vs1 = 0.56, 95% CI = 0.27 to 1.17, P-trend = .02). No association was evident for the other measured biomarkers. Conclusion: Study participants with higher circulating concentrations of vitamin B6 had lower risk of RCC and improved survival following diagnosis in two independent cohorts.

  • 224.
    Johansson, Mattias
    et al.
    International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Holmström, Benny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Hinchliffe, Sally R
    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.
    Wiklund, Fredrik
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Combining 33 genetic variants with prostate-specific antigen for prediction of prostate cancer: longitudinal study2012In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 130, no 1, p. 129-137Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate if a genetic risk score including 33 common genetic variants improves prediction of prostate cancer when added to measures of prostate-specific antigen (PSA). We conducted a case-control study nested within the Northern Sweden Health and Disease Cohort (NSHDC), a prospective cohort in northern Sweden. A total of 520 cases and 988 controls matched for age, and date of blood draw were identified by linkage between the regional cancer register and the NSHDC. Receiver operating characteristic curves with area under curve (AUC) estimates were used as measures of prostate cancer prediction. The AUC for the genetic risk score was 64.3% [95% confidence interval (CI) = 61.4-67.2], and the AUC for total PSA and the ratio of free to total PSA was 86.2% (95% CI = 84.4-88.1). A model including the genetic risk score, total PSA and the ratio of free to total PSA increased the AUC to 87.2% (95% CI = 85.4-89.0, p difference = 0.002). The addition of a genetic risk score to PSA resulted in a marginal improvement in prostate cancer prediction that would not seem useful for clinical risk assessment.

  • 225.
    Johansson, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. International Agency for Research on Cancer (IARC), Lyon, France.
    McKay, James D
    Wiklund, Fredrik
    Rinaldi, Sabina
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Bälter, Katarina
    Adami, Hans-Olov
    Grönberg, Henrik
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Kaaks, Rudolf
    Genetic variation in the SST gene and its receptors in relation to circulating levels of insulin-like growth factor-I, IGFBP3, and prostate cancer risk2009In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 18, no 5, p. 1644-1650Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Somatostatin (SST) and its receptors (SSTR1-5) may have a role in prostate cancer by influencing the IGFI hormone axis or through direct effects on prostate epithelia. We have investigated if genetic variation in the SST and SSTR1-5 genes influences prostate cancer risk and/or circulating IGFI and IGFBP3 hormone levels. MATERIALS AND METHODS: We analyzed 28 haplotype tagging single nucleotide polymorphisms in the SST and SSTR1-5 genes in a case-control/genetic association study to investigate the association between genetic variation and prostate cancer risk. The study included 2863 cases and 1737 controls from the Cancer Prostate in Sweden (CAPS) study. To investigate the genetic influence on circulating hormone levels, plasma concentrations of IGFI and IGFBP3 were analyzed in 874 controls of the CAPS study and 550 male subjects from the Northern Sweden Health and Disease Cohort (NSHDC). RESULTS: No clear association between prostate cancer risk and genetic variation of the SST and SSTR1-5 genes was identified. The SSTR5 missense single nucleotide polymorphism rs4988483 was associated with circulating IGFI (P = 0.002) and IGFBP3 (P = 0.0003) hormone levels in CAPS controls, with a per allele decrease of approximately 11%. This decrease was replicated in NSHDC for circulating IGFBP3 (P = 0.01) but not for IGFI (P = 0.09). Combining CAPS and NSHDC subjects indicated evidence of association between rs4988483 and both IGFBP3 (P = 2 x 10(-5)) and IGFI (P = 0.0004) hormone levels. CONCLUSIONS: Our results suggest that genetic variation in the SSTR5 gene and, particularly, the rs4988483 single nucleotide polymorphism influence circulating IGFI and IGFBP3 hormone levels with no measurable effect on prostate cancer risk. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1644-50).

  • 226. Johansson, Mattias
    et al.
    Relton, Caroline
    Ueland, Per Magne
    Vollset, Stein Emil
    Midttun, Øivind
    Nygård, Ottar
    Slimani, Nadia
    Boffetta, Paolo
    Jenab, Mazda
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Fagherazzi, Guy
    Kaaks, Rudolf
    Rohrmann, Sabine
    Boeing, Heiner
    Weikert, Cornelia
    Bueno-de-Mesquita, H Bas
    Ros, Martine M
    van Gils, Carla H
    Peeters, Petra H M
    Agudo, Antonio
    Barricarte, Aurelio
    Navarro, Carmen
    Rodríguez, Laudina
    Sánchez, Maria-José
    Larrañaga, Nerea
    Khaw, Kay-Tee
    Wareham, Nick
    Allen, Naomi E
    Crowe, Francesca
    Gallo, Valentina
    Norat, Teresa
    Krogh, Vittorio
    Masala, Giovanna
    Panico, Salvatore
    Sacerdote, Carlotta
    Tumino, Rosario
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Rasmuson, Torgny
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Riboli, Elio
    Vineis, Paolo
    Brennan, Paul
    Serum B vitamin levels and risk of lung cancer2010In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 303, no 23, p. 2377-2385Article in journal (Refereed)
    Abstract [en]

    CONTEXT: B vitamins and factors related to 1-carbon metabolism help to maintain DNA integrity and regulate gene expression and may affect cancer risk. OBJECTIVE: To investigate if 1-carbon metabolism factors are associated with onset of lung cancer. DESIGN, SETTING, AND PARTICIPANTS: The European Prospective Investigation into Cancer and Nutrition (EPIC) recruited 519,978 participants from 10 countries between 1992 and 2000, of whom 385,747 donated blood. By 2006, 899 lung cancer cases were identified and 1770 control participants were individually matched by country, sex, date of birth, and date of blood collection. Serum levels were measured for 6 factors of 1-carbon metabolism and cotinine. MAIN OUTCOME MEASURE: Odds ratios (ORs) of lung cancer by serum levels of 4 B vitamins (B(2), B(6), folate [B(9)], and B(12)), methionine, and homocysteine. RESULTS: Within the entire EPIC cohort, the age-standardized incidence rates of lung cancer (standardized to the world population, aged 35-79 years) were 6.6, 44.9, and 156.1 per 100,000 person-years among never, former, and current smokers for men, respectively. The corresponding incidence rates for women were 7.1, 23.9, and 100.9 per 100,000 person-years, respectively. After accounting for smoking, a lower risk for lung cancer was seen for elevated serum levels of B(6) (fourth vs first quartile OR, 0.44; 95% confidence interval [CI], 0.33-0.60; P for trend <.000001), as well as for serum methionine (fourth vs first quartile OR, 0.52; 95% CI, 0.39-0.69; P for trend <.000001). Similar and consistent decreases in risk were observed in never, former, and current smokers, indicating that results were not due to confounding by smoking. The magnitude of risk was also constant with increasing length of follow-up, indicating that the associations were not explained by preclinical disease. A lower risk was also seen for serum folate (fourth vs first quartile OR, 0.68; 95% CI, 0.51-0.90; P for trend = .001), although this was apparent only for former and current smokers. When participants were classified by median levels of serum methionine and B(6), having above-median levels of both was associated with a lower lung cancer risk overall (OR, 0.41; 95% CI, 0.31-0.54), as well as separately among never (OR, 0.36; 95% CI, 0.18-0.72), former (OR, 0.51; 95% CI, 0.34-0.76), and current smokers (OR, 0.42; 95% CI, 0.27-0.65). CONCLUSION: Serum levels of vitamin B(6) and methionine were inversely associated with risk of lung cancer.

  • 227.
    Johansson, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Vollset, Stein Emil
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Key, Tim
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Ueland, Per M
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Prospective investigation of one-carbon metabolism in relation to prostate cancer risk: results from the NSHDC studyManuscript (Other academic)
  • 228.
    Johansson, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Vollset, Stein Emil
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Key, Tim
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Midttun, Øivind
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Ueland, Per M
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    One-carbon metabolism and prostate cancer risk: prospective investigation of seven circulating B vitamins and metabolites2009In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 18, no 5, p. 1538-1543Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Components of one-carbon metabolism are believed to influence cancer development with suggested mechanisms, including DNA methylation and DNA repair mechanisms. However, few prospective studies have investigated one-carbon metabolism in relation to prostate cancer risk, and the results have been conflicting. The aim of this study was to do a comprehensive investigation of the components of one-carbon metabolism in relation to prostate cancer risk. A panel of seven circulating B vitamins and related metabolites was selected, most of which have not been studied before. MATERIALS AND METHODS: We analyzed plasma concentrations of betaine, choline, cysteine, methionine, methylmalonic acid (MMA), vitamin B2, and vitamin B6 in 561 cases and 1,034 controls matched for age and recruitment date, nested within the population-based Northern Sweden Health and Disease Cohort. Relative risks of prostate cancer were estimated by conditional logistic regression. RESULTS: Positive associations with prostate cancer risk were observed for choline and vitamin B2, and an inverse association was observed for MMA. The relative risks for a doubling in concentrations were 1.46 [95% confidence interval (95% CI), 1.04-2.05; P(trend) = 0.03] for choline, 1.11 (95% CI, 1.00-1.23; P(trend) = 0.04) for vitamin B2, and 0.78 (95% CI, 0.63-0.97; P(trend) = 0.03) for MMA. Concentrations of betaine, cysteine, methionine, and vitamin B6 were not associated with prostate cancer risk. CONCLUSION: The results of this large prospective study suggest that elevated plasma concentrations of choline and vitamin B2 may be associated with an increased risk of prostate cancer. These novel findings support a role of one-carbon metabolism in prostate cancer etiology and warrant further investigation. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1538-43).

  • 229. Jonsson, Karin
    et al.
    Andersson, Roger
    Knudsen, Knud Erik Bach
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hanhineva, Kati
    Katina, Kati
    Kolehmainen, Marjukka
    Kyrø, Cecilie
    Langton, Maud
    Nordlund, Emilia
    Lærke, Helle Nygaard
    Olsen, Anja
    Poutanen, Kajsa
    Tjønneland, Anne
    Landberg, Rikard
    Rye and health - Where do we stand and where do we go?2018In: Trends in Food Science & Technology, ISSN 0924-2244, E-ISSN 1879-3053, Vol. 79, p. 78-87Article, review/survey (Refereed)
    Abstract [en]

    Background: High whole grain intake has consistently been associated with lowered risk of developing a number of chronic diseases. Among cereals, rye has highest content of dietary fiber, together with a wide variety of bioactive compounds. There is accumulating evidence from intervention studies of physiological effects of rye foods with potential health benefits.

    Scope and approach: This review summarizes the state of the art of rye and health and identifies future directions for research and innovation, based partly on findings presented at the international conference "The Power of Rye", angstrom land, Finland, 7-8 June 2017.

    Key findings and conclusions: Rye foods have well-established beneficial effects on insulin metabolism compared with wheat bread under isocaloric conditions and at standardized amounts of available carbohydrates, which may have positive implications for diabetes prevention. Recent findings suggest that alterations in blood glucose flux partly explain these effects. Moreover, several studies have shown beneficial effects of rye-based foods on satiety, which is one plausible mechanism behind recently demonstrated beneficial effects on weight management. Emerging results indicate beneficial effects of rye intake on inflammation and blood lipids. More research is needed to uncover underlying mechanisms for other demonstrated effects and the long-term implications for health. A challenge with rye-based foods is making them palatable and widely acceptable to consumers. Development of innovative and tasty rye products and targeted communication strategies is crucial in increasing awareness and consumption of rye foods. Novel results in this regard are presented in this review.

  • 230. Justice, Anne E
    et al.
    Winkler, Thomas W
    Feitosa, Mary F
    Graff, Misa
    Fisher, Virginia A
    Young, Kristin
    Barata, Llilda
    Deng, Xuan
    Czajkowski, Jacek
    Hadley, David
    Ngwa, Julius S
    Ahluwalia, Tarunveer S
    Chu, Audrey Y
    Heard-Costa, Nancy L
    Lim, Elise
    Perez, Jeremiah
    Eicher, John D
    Kutalik, Zoltan
    Xue, Luting
    Mahajan, Anubha
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, SE-205 02 Malmö, Sweden.
    Wu, Joseph
    Qi, Qibin
    Ahmad, Shafqat
    Alfred, Tamuno
    Amin, Najaf
    Bielak, Lawrence F
    Bonnefond, Amelie
    Bragg, Jennifer
    Cadby, Gemma
    Chittani, Martina
    Coggeshall, Scott
    Corre, Tanguy
    Direk, Nese
    Eriksson, Joel
    Fischer, Krista
    Gorski, Mathias
    Neergaard Harder, Marie
    Horikoshi, Momoko
    Huang, Tao
    Huffman, Jennifer E
    Jackson, Anne U
    Justesen, Johanne Marie
    Kanoni, Stavroula
    Kinnunen, Leena
    Kleber, Marcus E
    Komulainen, Pirjo
    Kumari, Meena
    Lim, Unhee
    Luan, Jian'an
    Lyytikainen, Leo-Pekka
    Mangino, Massimo
    Manichaikul, Ani
    Marten, Jonathan
    Middelberg, Rita P S
    Muller-Nurasyid, Martina
    Navarro, Pau
    Perusse, Louis
    Pervjakova, Natalia
    Sarti, Cinzia
    Smith, Albert Vernon
    Smith, Jennifer A
    Stancakova, Alena
    Strawbridge, Rona J
    Stringham, Heather M
    Sung, Yun Ju
    Tanaka, Toshiko
    Teumer, Alexander
    Trompet, Stella
    van der Laan, Sander W
    van der Most, Peter J
    Van Vliet-Ostaptchouk, Jana V
    Vedantam, Sailaja L
    Verweij, Niek
    Vink, Jacqueline M
    Vitart, Veronique
    Wu, Ying
    Yengo, Loic
    Zhang, Weihua
    Hua Zhao, Jing
    Zimmermann, Martina E
    Zubair, Niha
    Abecasis, Goncalo R
    Adair, Linda S
    Afaq, Saima
    Afzal, Uzma
    Bakker, Stephan J L
    Bartz, Traci M
    Beilby, John
    Bergman, Richard N
    Bergmann, Sven
    Biffar, Reiner
    Blangero, John
    Boerwinkle, Eric
    Bonnycastle, Lori L
    Bottinger, Erwin
    Braga, Daniele
    Buckley, Brendan M
    Buyske, Steve
    Campbell, Harry
    Chambers, John C
    Collins, Francis S
    Curran, Joanne E
    de Borst, Gert J
    de Craen, Anton J M
    de Geus, Eco J C
    Dedoussis, George
    Delgado, Graciela E
    den Ruijter, Hester M
    Eiriksdottir, Gudny
    Eriksson, Anna L
    Esko, Tonu
    Faul, Jessica D
    Ford, Ian
    Forrester, Terrence
    Gertow, Karl
    Gigante, Bruna
    Glorioso, Nicola
    Gong, Jian
    Grallert, Harald
    Grammer, Tanja B
    Grarup, Niels
    Haitjema, Saskia
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hamsten, Anders
    Hansen, Torben
    Harris, Tamara B
    Hartman, Catharina A
    Hassinen, Maija
    Hastie, Nicholas D
    Heath, Andrew C
    Hernandez, Dena
    Hindorff, Lucia
    Hocking, Lynne J
    Hollensted, Mette
    Holmen, Oddgeir L
    Homuth, Georg
    Jan Hottenga, Jouke
    Huang, Jie
    Hung, Joseph
    Hutri-Kahonen, Nina
    Ingelsson, Erik
    James, Alan L
    Jansson, John-Olov
    Jarvelin, Marjo-Riitta
    Jhun, Min A
    Jorgensen, Marit E
    Juonala, Markus
    Kahonen, Mika
    Karlsson, Magnus
    Koistinen, Heikki A
    Kolcic, Ivana
    Kolovou, Genovefa
    Kooperberg, Charles
    Kramer, Bernhard K
    Kuusisto, Johanna
    Kvaloy, Kirsti
    Lakka, Timo A
    Langenberg, Claudia
    Launer, Lenore J
    Leander, Karin
    Lee, Nanette R
    Lind, Lars
    Lindgren, Cecilia M
    Linneberg, Allan
    Lobbens, Stephane
    Loh, Marie
    Lorentzon, Mattias
    Luben, Robert
    Lubke, Gitta
    Ludolph-Donislawski, Anja
    Lupoli, Sara
    Madden, Pamela A F
    Mannikko, Reija
    Marques-Vidal, Pedro
    Martin, Nicholas G
    McKenzie, Colin A
    McKnight, Barbara
    Mellstrom, Dan
    Menni, Cristina
    Montgomery, Grant W
    Musk, Aw Bill
    Narisu, Narisu
    Nauck, Matthias
    Nolte, Ilja M
    Oldehinkel, Albertine J
    Olden, Matthias
    Ong, Ken K
    Padmanabhan, Sandosh
    Peyser, Patricia A
    Pisinger, Charlotta
    Porteous, David J
    Raitakari, Olli T
    Rankinen, Tuomo
    Rao, D C
    Rasmussen-Torvik, Laura J
    Rawal, Rajesh
    Rice, Treva
    Ridker, Paul M
    Rose, Lynda M
    Bien, Stephanie A
    Rudan, Igor
    Sanna, Serena
    Sarzynski, Mark A
    Sattar, Naveed
    Savonen, Kai
    Schlessinger, David
    Scholtens, Salome
    Schurmann, Claudia
    Scott, Robert A
    Sennblad, Bengt
    Siemelink, Marten A
    Silbernagel, Gunther
    Slagboom, P Eline
    Snieder, Harold
    Staessen, Jan A
    Stott, David J
    Swertz, Morris A
    Swift, Amy J
    Taylor, Kent D
    Tayo, Bamidele O
    Thorand, Barbara
    Thuillier, Dorothee
    Tuomilehto, Jaakko
    Uitterlinden, Andre G
    Vandenput, Liesbeth
    Vohl, Marie-Claude
    Volzke, Henry
    Vonk, Judith M
    Waeber, Gerard
    Waldenberger, Melanie
    Westendorp, R G J
    Wild, Sarah
    Willemsen, Gonneke
    Wolffenbuttel, Bruce H R
    Wong, Andrew
    Wright, Alan F
    Zhao, Wei
    Zillikens, M Carola
    Baldassarre, Damiano
    Balkau, Beverley
    Bandinelli, Stefania
    Boger, Carsten A
    Boomsma, Dorret I
    Bouchard, Claude
    Bruinenberg, Marcel
    Chasman, Daniel I
    Chen, Yii-DerIda
    Chines, Peter S
    Cooper, Richard S
    Cucca, Francesco
    Cusi, Daniele
    Faire, Ulf de
    Ferrucci, Luigi
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, SE-205 02 Malmö, Sweden; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.
    Froguel, Philippe
    Gordon-Larsen, Penny
    Grabe, Hans-Jorgen
    Gudnason, Vilmundur
    Haiman, Christopher A
    Hayward, Caroline
    Hveem, Kristian
    Johnson, Andrew D
    Wouter Jukema, J
    Kardia, Sharon L R
    Kivimaki, Mika
    Kooner, Jaspal S
    Kuh, Diana
    Laakso, Markku
    Lehtimaki, Terho
    Marchand, Loic Le
    Marz, Winfried
    McCarthy, Mark I
    Metspalu, Andres
    Morris, Andrew P
    Ohlsson, Claes
    Palmer, Lyle J
    Pasterkamp, Gerard
    Pedersen, Oluf
    Peters, Annette
    Peters, Ulrike
    Polasek, Ozren
    Psaty, Bruce M
    Qi, Lu
    Rauramaa, Rainer
    Smith, Blair H
    Sorensen, Thorkild I A
    Strauch, Konstantin
    Tiemeier, Henning
    Tremoli, Elena
    van der Harst, Pim
    Vestergaard, Henrik
    Vollenweider, Peter
    Wareham, Nicholas J
    Weir, David R
    Whitfield, John B
    Wilson, James F
    Tyrrell, Jessica
    Frayling, Timothy M
    Barroso, Ines
    Boehnke, Michael
    Deloukas, Panagiotis
    Fox, Caroline S
    Hirschhorn, Joel N
    Hunter, David J
    Spector, Tim D
    Strachan, David P
    van Duijn, Cornelia M
    Heid, Iris M
    Mohlke, Karen L
    Marchini, Jonathan
    Loos, Ruth J F
    Kilpelainen, Tuomas O
    Liu, Ching-Ti
    Borecki, Ingrid B
    North, Kari E
    Cupples, L Adrienne
    Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits2017In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, p. 14977-14977Article in journal (Refereed)
    Abstract [en]

    Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.

  • 231. Kaaks, Rudolf
    et al.
    Sookthai, Disorn
    Hemminki, Kari
    Kraemer, Alwin
    Boeing, Heiner
    Wirfalt, Elisabet
    Weiderpass, Elisabete
    Overvad, Kim
    Tjonneland, Anne
    Olsen, Anja
    Peeters, Petra H.
    Bueno-de-Mesquita, H. B. (As)
    Panico, Salvatore
    Pala, Valeria
    Vineis, Paolo
    Ramon Quiros, J.
    Ardanaz, Eva
    Sanchez, Maria-Jose
    Chirlaque, Maria-Dolores
    Larranaga, Nerea
    Brennan, Paul
    Trichopoulos, Dimitrios
    Trichopoulou, Antonia
    Lagiou, Pagona
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Khaw, Kay-Tee
    Key, Timothy J.
    Riboli, Elio
    Canzian, Federico
    Risk factors for cancers of unknown primary site: Results from the prospective EPIC cohort2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 135, no 10, p. 2475-2481Article in journal (Refereed)
    Abstract [en]

    Cancer of unknown primary site (CUP) may be called an orphan disease, as it is diagnosed when metastases are detected while the primary tumor typically remains undetected, and because little research has been done on its primary causes. So far, few epidemiological studies, if any, have addressed possible risk factors for CUP. We analyzed data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (N=476,940). During prospective follow-up, a total of 651 cases of incident cases of CUP were detected (ICD-O-2 code C809). Proportional hazards models were conducted to examine the associations of lifetime history of smoking habits, alcohol consumption, levels of education and anthropometric indices of adiposity with risk of being diagnosed with CUP. Risk of being diagnosed with CUP was strongly related to smoking, with a relative risk of 3.66 [95% C.I., 2.24-5.97] for current, heavy smokers (26+ cigarettes/day) compared to never smokers (adjusted for alcohol consumption, body mass index, waist circumference and level of education) and a relative risk of 5.12 [3.09-8.47] for cases with CUP who died within 12 months. For alcohol consumption and level of education, weaker associations were observed but attenuated and no longer statistically significant after adjusting for smoking and indices of obesity. Finally, risk of CUP was increased by approximately 30 per cent for subjects in the highest versus lowest quartiles of waist circumference. Our analyses provide further documentation, in addition to autopsy studies, that a substantial proportion of cancers of unknown primary site may have their origin in smoking-related tumors, in particular. What's new? When cancer appears as metastatic disease but no primary tumor can be observed, it's called cancer of unknown primary site. Little is known about the risk factors for this type of cancer. This study analyzed data from a European cohort and discovered a strong association between smoking and these cancers. Other risk factors they identified were drinking alcohol and being fat. This is the first epidemiological study of these type of cancers, and it strengthens the observations from autopsy studies that many of these cancers of unknown primary site stem from smoking-related tumors.

  • 232. Kaaks, Rudolf
    et al.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Villar, Stéphanie
    Poetsch, Anna R
    Dossus, Laure
    Nieters, Alexandra
    Riboli, Elio
    Palmqvist, Richard
    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.
    Plass, Christoph
    Friesen, Marlin D
    Insulin-like Growth Factor-II Methylation Status in Lymphocyte DNA and Colon Cancer Risk in the Northern Sweden Health and Disease Cohort2009In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 69, no 13, p. 5400-5405Article in journal (Refereed)
    Abstract [en]

    Loss of imprinting (LOI) of the insulin-like growth factor II (IGFII) gene is a frequent phenomenon in colorectal tumor tissues. Previous reports indicated that subjects with colorectal neoplasias show LOI of IGFII in circulating lymphocytes. Furthermore, LOI of IGFII is strongly related to the methylation of a differentially methylated region (DMR) in intron 2 of IGFII, suggesting that the methylation status could serve as a biomarker for early detection. Thus, hypermethylation of this DMR, even at a systemic level, e.g., in lymphocyte DNA, could be used for screening for colon cancer. To validate this, we performed a case-control study of 97 colon cancer cases and 190 age-matched and gender-matched controls, nested within the prospective Northern Sweden Health and Disease Study cohort. Methylation levels of the IGFII-DMR in lymphocyte DNA were measured at two specific CpG sites of the IGFII-DMR using a mass-spectrometric method called short oligonucleotide mass analysis, the measurements of which showed high reproducibility between replicate measurements for the two CpG sites combined and showed almost perfect validity when performed on variable mixtures of methylated and unmethylated standards. Mean fractions of CpG methylation, for the two CpG sites combined, were identical for cases and controls (0.47 and 0.46, respectively; Pdifference = 0.75), and logistic regression analyses showed no relationship between colon cancer risk and quartile levels of CpG methylation. The results from this study population do not support the hypothesis that colon cancer can be predicted from the different degrees of methylation of DMR in the IGFII gene from lymphocyte DNA. [Cancer Res 2009;69(13):5400-5].

  • 233. Kanoni, Stavroula
    et al.
    Nettleton, Jennifer A
    Hivert, Marie-France
    Ye, Zheng
    van Rooij, Frank JA
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Odontology. Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Sonestedt, Emily
    Ngwa, Julius S
    Wojczynski, Mary K
    Lemaitre, Rozenn N
    Gustafsson, Stefan
    Anderson, Jennifer S
    Tanaka, Toshiko
    Hindy, George
    Saylor, Georgia
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts.
    Bennett, Amanda J
    van Duijn, Cornelia M
    Florez, Jose C
    Fox, Caroline S
    Hofman, Albert
    Hoogeveen, Ron C
    Houston, Denise K
    Hu, Frank B
    Jacques, Paul F
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lind, Lars
    Liu, Yongmei
    McKeown, Nicola
    Ordovas, Jose
    Pankow, James S
    Sijbrands, Eric JG
    Syvänen, Ann-Christine
    Uitterlinden, André G
    Yannakoulia, Mary
    Zillikens, M Carola
    Wareham, Nick J
    Prokopenko, Inga
    Bandinelli, Stefania
    Forouhi, Nita G
    Cupples, L Adrienne
    Loos, Ruth J
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Dupuis, Josée
    Langenberg, Claudia
    Ferrucci, Luigi
    Kritchevsky, Stephen B
    McCarthy, Mark I
    Ingelsson, Erik
    Borecki, Ingrid B
    Witteman, Jacqueline CM
    Orho-Melander, Marju
    Siscovick, David S
    Meigs, James B
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts.
    Dedoussis, George V
    Total zinc intake may modify the glucose-raising effect of a zinc transporter (SLC30A8) variant: a 14-cohort meta-analysis2011In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 60, no 9, p. 2407-2416Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE Many genetic variants have been associated with glucose homeostasis and type 2 diabetes in genome-wide association studies. Zinc is an essential micronutrient that is important for β-cell function and glucose homeostasis. We tested the hypothesis that zinc intake could influence the glucose-raising effect of specific variants.

    RESEARCH DESIGN AND METHODS We conducted a 14-cohort meta-analysis to assess the interaction of 20 genetic variants known to be related to glycemic traits and zinc metabolism with dietary zinc intake (food sources) and a 5-cohort meta-analysis to assess the interaction with total zinc intake (food sources and supplements) on fasting glucose levels among individuals of European ancestry without diabetes.

    RESULTS We observed a significant association of total zinc intake with lower fasting glucose levels (β-coefficient ± SE per 1 mg/day of zinc intake: -0.0012 ± 0.0003 mmol/L, summary P value = 0.0003), while the association of dietary zinc intake was not significant. We identified a nominally significant interaction between total zinc intake and the SLC30A8 rs11558471 variant on fasting glucose levels (β-coefficient ± SE per A allele for 1 mg/day of greater total zinc intake: -0.0017 ± 0.0006 mmol/L, summary interaction P value = 0.005); this result suggests a stronger inverse association between total zinc intake and fasting glucose in individuals carrying the glucose-raising A allele compared with individuals who do not carry it. None of the other interaction tests were statistically significant.

    CONCLUSIONS Our results suggest that higher total zinc intake may attenuate the glucose-raising effect of the rs11558471 SLC30A8 (zinc transporter) variant. Our findings also support evidence for the association of higher total zinc intake with lower fasting glucose levels.

  • 234. Key, T J
    et al.
    Appleby, P N
    Reeves, G K
    Roddam, A W
    Helzlsouer, K J
    Alberg, A J
    Rollison, D E
    Dorgan, J F
    Brinton, L A
    Overvad, K
    Kaaks, R
    Trichopoulou, A
    Clavel-Chapelon, F
    Panico, S
    Duell, E J
    Peeters, P H M
    Rinaldi, S
    Fentiman, I S
    Dowsett, M
    Manjer, J
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Baglietto, L
    English, D R
    Giles, G G
    Hopper, J L
    Severi, G
    Morris, H A
    Hankinson, S E
    Tworoger, S S
    Koenig, K
    Zeleniuch-Jacquotte, A
    Arslan, A A
    Toniolo, P
    Shore, R E
    Krogh, V
    Micheli, A
    Berrino, F
    Barrett-Connor, E
    Laughlin, G A
    Kabuto, M
    Akiba, S
    Stevens, R G
    Neriishi, K
    Land, C E
    Cauley, J A
    Lui, Li Yung
    Cummings, Steven R
    Gunter, M J
    Rohan, T E
    Strickler, H D
    Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies.2011In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 105, no 5, p. 709-722Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood.

    METHODS: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies.

    RESULTS: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer.

    CONCLUSION: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk.

  • 235. Key, Timothy J
    et al.
    Allen, Naomi
    Appleby, Paul
    Overvad, Kim
    Tjönneland, Anne
    Miller, Anthony
    Boeing, Heiner
    Karalis, Dimitrios
    Psaltopoulou, Theodora
    Berrino, Franco
    Palli, Domenico
    Panico, Salvatore
    Tumino, Rosario
    Vineis, Paolo
    Bueno-De-Mesquita, H B
    Kiemeney, Lambertus
    Peeters, Petra H M
    Martinez, Carmen
    Dorronsoro, Miren
    Gonzalez, Carlos A
    Chirlaque, M D
    Quiros, J Ramon
    Ardanaz, Eva
    Berglund, Göran
    Egevad, Lars
    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. Urologi och andrologi.
    Bingham, Sheila
    Day, Nicholas
    Gann, Peter
    Kaaks, Rudolf
    Ferrari, Pietro
    Riboli, Elio
    Fruits and vegetables and prostate cancer: no association among 1104 cases in a prospective study of 130544 men in the European Prospective Investigation into Cancer and Nutrition (EPIC).2004In: International Journal of Cancer, ISSN 0020-7136, Vol. 109, no 1, p. 119-24Article in journal (Refereed)
  • 236. Key, Timothy J
    et al.
    Appleby, Paul N
    Allen, Naomi E
    Travis, Ruth C
    Roddam, Andrew W
    Jenab, Mazda
    Egevad, Lars
    Tjønneland, Anne
    Johnsen, Nina F
    Overvad, Kim
    Linseisen, Jakob
    Rohrmann, Sabine
    Boeing, Heiner
    Pischon, Tobias
    Psaltopoulou, Theodora
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Palli, Domenico
    Vineis, Paolo
    Tumino, Rosario
    Berrino, Franco
    Kiemeney, Lambertus
    Bueno-de-Mesquita, H Bas
    Quirós, J Ramón
    González, Carlos A
    Martinez, Carmen
    Larrañaga, Nerea
    Chirlaque, María Dolores
    Ardanaz, Eva
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Urologi och andrologi.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Khaw, Kay-Tee
    Bingham, Sheila
    Slimani, Nadia
    Ferrari, Pietro
    Rinaldi, Sabina
    Riboli, Elio
    Plasma carotenoids, retinol, and tocopherols and the risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition study.2007In: American Journal of Clinical Nutrition, ISSN 0002-9165, Vol. 86, no 3, p. 672-81Article in journal (Refereed)
  • 237. Khan, Aneire E
    et al.
    Gallo, Valentina
    Linseisen, Jakob
    Kaaks, Rudolf
    Rohrmann, Sabine
    Raaschou-Nielsen, Ole
    Tjønneland, Anne
    Johnsen, Hans E
    Overvad, Kim
    Bergmann, Manuela M
    Boeing, Heiner
    Benetou, Vasiliki
    Psaltopoulou, Theodora
    Trichopoulou, Antonia
    Masala, Giovanna
    Mattiello, Amalia
    Grioni, Sara
    Tumino, Rosario
    Vermeulen, Roel C H
    Peeters, Petra H M
    Bueno-de-Mesquita, H Bas
    Ros, Martine M
    Lund, Eiliv
    Ardanaz, Eva
    Chirlaque, María-Dolores
    Jakszyn, Paula
    Larrañaga, Nerea
    Losada, Adamina
    Becker, Nikolaus
    Nieters, Alexandra
    Martínez-García, Carmen
    Ågren, Åsa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Berglund, Göran
    Manjer, Jonas
    Allen, Naomi E
    Key, Timothy J
    Bingham, Sheila
    Khaw, Kay Tee
    Slimani, Nadia
    Ferrari, Pietro
    Boffetta, Paolo
    Norat, Teresa
    Vineis, Paolo
    Riboli, Elio
    Diabetes and the risk of non-Hodgkin's lymphoma and multiple myeloma in the European prospective investigation into Cancer and nutrition2008In: Haematologica (online), ISSN 0390-6078, E-ISSN 1592-8721, Vol. 93, no 6, p. 842-850Article in journal (Refereed)
  • 238. Kilpeläinen, Tuomas O
    et al.
    Qi, Lu
    Brage, Soren
    Sharp, Stephen J
    Sonestedt, Emily
    Demerath, Ellen
    Ahmad, Tariq
    Mora, Samia
    Kaakinen, Marika
    Sandholt, Camilla Helene
    Holzapfel, Christina
    Autenrieth, Christine S
    Hyppönen, Elina
    Cauchi, Stéphane
    He, Meian
    Kutalik, Zoltan
    Kumari, Meena
    Stančáková, Alena
    Meidtner, Karina
    Balkau, Beverley
    Tan, Jonathan T
    Mangino, Massimo
    Timpson, Nicholas J
    Song, Yiqing
    Zillikens, M Carola
    Jablonski, Kathleen A
    Garcia, Melissa E
    Johansson, Stefan
    Bragg-Gresham, Jennifer L
    Wu, Ying
    van Vliet-Ostaptchouk, Jana V
    Onland-Moret, N Charlotte
    Zimmermann, Esther
    Rivera, Natalia V
    Tanaka, Toshiko
    Stringham, Heather M
    Silbernagel, Günther
    Kanoni, Stavroula
    Feitosa, Mary F
    Snitker, Soren
    Ruiz, Jonatan R
    Metter, Jeffery
    Larrad, Maria Teresa Martinez
    Atalay, Mustafa
    Hakanen, Maarit
    Amin, Najaf
    Cavalcanti-Proença, Christine
    Grøntved, Anders
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Jansson, John-Olov
    Kuusisto, Johanna
    Kähönen, Mika
    Lutsey, Pamela L
    Nolan, John J
    Palla, Luigi
    Pedersen, Oluf
    Pérusse, Louis
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Scott, Robert A
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sovio, Ulla
    Tammelin, Tuija H
    Rönnemaa, Tapani
    Lakka, Timo A
    Uusitupa, Matti
    Rios, Manuel Serrano
    Ferrucci, Luigi
    Bouchard, Claude
    Meirhaeghe, Aline
    Fu, Mao
    Walker, Mark
    Borecki, Ingrid B
    Dedoussis, George V
    Fritsche, Andreas
    Ohlsson, Claes
    Boehnke, Michael
    Bandinelli, Stefania
    van Duijn, Cornelia M
    Ebrahim, Shah
    Lawlor, Debbie A
    Gudnason, Vilmundur
    Harris, Tamara B
    Sørensen, Thorkild I A
    Mohlke, Karen L
    Hofman, Albert
    Uitterlinden, André G
    Tuomilehto, Jaakko
    Lehtimäki, Terho
    Raitakari, Olli
    Isomaa, Bo
    Njølstad, Pål R
    Florez, Jose C
    Liu, Simin
    Ness, Andy
    Spector, Timothy D
    Tai, E Shyong
    Froguel, Philippe
    Boeing, Heiner
    Laakso, Markku
    Marmot, Michael
    Bergmann, Sven
    Power, Chris
    Khaw, Kay-Tee
    Chasman, Daniel
    Ridker, Paul
    Hansen, Torben
    Monda, Keri L
    Illig, Thomas
    Järvelin, Marjo-Riitta
    Wareham, Nicholas J
    Hu, Frank B
    Groop, Leif C
    Orho-Melander, Marju
    Ekelund, Ulf
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Loos, Ruth J F
    Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children2011In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 8, no 11, p. e1001116-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268).

    METHODS AND FINDINGS: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction)  = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio  = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio  = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents.

    CONCLUSIONS: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.

  • 239. Kitahara, Cari M
    et al.
    Wang, Sophia S
    Melin, Beatrice S
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wang, Zhaoming
    Braganza, Melissa
    Inskip, Peter D
    Albanes, Demetrius
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Beane Freeman, Laura E
    Buring, Julie E
    Carreón, Tania
    Feychting, Maria
    Gapstur, Susan M
    Gaziano, J Michael
    Giles, Graham G
    Hallmans, Goran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hankinson, Susan E
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hsing, Ann W
    Johansen, Christoffer
    Linet, Martha S
    McKean-Cowdin, Roberta
    Michaud, Dominique S
    Peters, Ulrike
    Purdue, Mark P
    Rothman, Nathaniel
    Ruder, Avima M
    Sesso, Howard D
    Severi, Gianluca
    Shu, Xiao-Ou
    Stevens, Victoria L
    Visvanathan, Kala
    Waters, Martha A
    White, Emily
    Wolk, Alicja
    Zeleniuch-Jacquotte, Anne
    Zheng, Wei
    Hoover, Robert
    Fraumeni, Joseph F
    Chatterjee, Nilanjan
    Yeager, Meredith
    Chanock, Stephen J
    Hartge, Patricia
    Rajaraman, Preetha
    Association between adult height, genetic susceptibility and risk of glioma.2012In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 41, no 4, p. 1075-1085Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Some, but not all, observational studies have suggested that taller stature is associated with a significant increased risk of glioma. In a pooled analysis of observational studies, we investigated the strength and consistency of this association, overall and for major sub-types, and investigated effect modification by genetic susceptibility to the disease. METHODS: We standardized and combined individual-level data on 1354 cases and 4734 control subjects from 13 prospective and 2 case-control studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for glioma and glioma sub-types were estimated using logistic regression models stratified by sex and adjusted for birth cohort and study. Pooled ORs were additionally estimated after stratifying the models according to seven recently identified glioma-related genetic variants. RESULTS: Among men, we found a positive association between height and glioma risk (≥190 vs 170-174 cm, pooled OR = 1.70, 95% CI: 1.11-2.61; P-trend = 0.01), which was slightly stronger after restricting to cases with glioblastoma (pooled OR = 1.99, 95% CI: 1.17-3.38; P-trend = 0.02). Among women, these associations were less clear (≥175 vs 160-164 cm, pooled OR for glioma = 1.06, 95% CI: 0.70-1.62; P-trend = 0.22; pooled OR for glioblastoma = 1.36, 95% CI: 0.77-2.39; P-trend = 0.04). In general, we did not observe evidence of effect modification by glioma-related genotypes on the association between height and glioma risk. CONCLUSION: An association of taller adult stature with glioma, particularly for men and stronger for glioblastoma, should be investigated further to clarify the role of environmental and genetic determinants of height in the etiology of this disease.

  • 240. Klein, Alison P.
    et al.
    Lindström, Sara
    Mendelsohn, Julie B.
    Steplowski, Emily
    Arslan, Alan A.
    Bueno-de-Mesquita, H. Bas
    Fuchs, Charles S.
    Gallinger, Steven
    Gross, Myron
    Helzlsouer, Kathy
    Holly, Elizabeth A.
    Jacobs, Eric J.
    Lacroix, Andrea
    Li, Donghui
    Mandelson, Margaret T.
    Olson, Sara H.
    Petersen, Gloria M.
    Risch, Harvey A.
    Stolzenberg-Solomon, Rachael Z.
    Zheng, Wei
    Amundadottir, Laufey
    Albanes, Demetrius
    Allen, Naomi E.
    Bamlet, William R.
    Boutron-Ruault, Marie-Christine
    Buring, Julie E.
    Bracci, Paige M.
    Canzian, Federico
    Clipp, Sandra
    Cotterchio, Michelle
    Duell, Eric J.
    Elena, Joanne
    Gaziano, J. Michael
    Giovannucci, Edward L.
    Goggins, Michael
    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.
    Hassan, Manal
    Hutchinson, Amy
    Hunter, David J.
    Kooperberg, Charles
    Kurtz, Robert C.
    Liu, Simin
    Overvad, Kim
    Palli, Domenico
    Patel, Alpa V.
    Rabe, Kari G.
    Shu, Xiao-Ou
    Slimani, Nadia
    Tobias, Geoffrey S.
    Trichopoulos, Dimitrios
    Van Den Eeden, Stephen K.
    Vineis, Paolo
    Virtamo, Jarmo
    Wactawski-Wende, Jean
    Wolpin, Brian M.
    Yu, Herbert
    Yu, Kai
    Zeleniuch-Jacquotte, Anne
    Chanock, Stephen J.
    Hoover, Robert N.
    Hartge, Patricia
    Kraft, Peter
    An absolute risk model to identify individuals at elevated risk for pancreatic cancer in the general population.2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 9, article id e72311Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We developed an absolute risk model to identify individuals in the general population at elevated risk of pancreatic cancer.

    PATIENTS AND METHODS: Using data on 3,349 cases and 3,654 controls from the PanScan Consortium, we developed a relative risk model for men and women of European ancestry based on non-genetic and genetic risk factors for pancreatic cancer. We estimated absolute risks based on these relative risks and population incidence rates.

    RESULTS: Our risk model included current smoking (multivariable adjusted odds ratio (OR) and 95% confidence interval: 2.20 [1.84-2.62]), heavy alcohol use (>3 drinks/day) (OR: 1.45 [1.19-1.76]), obesity (body mass index >30 kg/m(2)) (OR: 1.26 [1.09-1.45]), diabetes >3 years (nested case-control OR: 1.57 [1.13-2.18], case-control OR: 1.80 [1.40-2.32]), family history of pancreatic cancer (OR: 1.60 [1.20-2.12]), non-O ABO genotype (AO vs. OO genotype) (OR: 1.23 [1.10-1.37]) to (BB vs. OO genotype) (OR 1.58 [0.97-2.59]), rs3790844(chr1q32.1) (OR: 1.29 [1.19-1.40]), rs401681(5p15.33) (OR: 1.18 [1.10-1.26]) and rs9543325(13q22.1) (OR: 1.27 [1.18-1.36]). The areas under the ROC curve for risk models including only non-genetic factors, only genetic factors, and both non-genetic and genetic factors were 58%, 57% and 61%, respectively. We estimate that fewer than 3/1,000 U.S. non-Hispanic whites have more than a 5% predicted lifetime absolute risk.

    CONCLUSION: Although absolute risk modeling using established risk factors may help to identify a group of individuals at higher than average risk of pancreatic cancer, the immediate clinical utility of our model is limited. However, a risk model can increase awareness of the various risk factors for pancreatic cancer, including modifiable behaviors.

  • 241. Klingberg, Sofia
    et al.
    Ellegård, Lars
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    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 Public Health Sciences.
    Andersson, Henrik
    Winkvist, Anna
    Inverse relation between dietary intake of naturally occurring plant sterols and serum cholesterol in northern Sweden2008In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 87, no 4, p. 993-1001Article in journal (Refereed)
    Abstract [en]

    Background: Plant sterols are bioactive compounds, found in all vegetable foods, which inhibit cholesterol absorption. Little is known about the effect of habitual natural dietary intake of plant sterols.

    Objective: We investigated the relation between plant sterol density (in mg/MJ) and serum concentrations of cholesterol in men and women in northern Sweden.

    Design: The analysis included 37 150 men and 40 502 women aged 29–61 y, all participants in the Västerbotten Intervention Program.

    Results: Higher plant sterol density was associated with lower serum total cholesterol in both sexes and with lower LDL cholesterol in women. After adjustment for age, body mass index (in kg/m2), and (in women) menopausal status, men with high plant sterol density (quintile 5) had 0.15 mmol/L (2.6%) lower total serum cholesterol (P for trend = 0.001) and 0.13 mmol/L (3.1%) lower LDL cholesterol (P = 0.062) than did men with low plant sterol density (quintile 1). The corresponding figures for women were 0.20 mmol/L (3.5%) lower total serum cholesterol (P for trend < 0.001) and 0.13 mmol/L (3.2%) lower LDL cholesterol (Pfor trend = 0.001).

    Conclusions: The present study is the second epidemiologic study to show a significant inverse relation between naturally occurring dietary plant sterols and serum cholesterol. To the extent that the associations found truly mirror plant sterol intake and not merely a diet high in vegetable fat and fiber, it highlights the importance of considering the plant sterol content of foods both in primary prevention of cardiovascular disease and in the dietary advice incorporated into nutritional treatment of patients with hyperlipidemia.

  • 242.
    Klingberg, Sofia
    et al.
    Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg.
    Ellegård, Lars
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology. 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.
    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.
    Winkvist, Anna
    Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg.
    Dietary intake of naturally occurring plant sterols is related to a lower risk of a first myocardial infarction in men but not in women in northern sweden2013In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 143, no 10, p. 1630-1635Article in journal (Refereed)
    Abstract [en]

    Dietary intake of naturally occurring plant sterols is inversely related to serum cholesterol concentrations. Elevated serum cholesterol increases the risk of myocardial infarction (MI), but it is unknown if this can be reduced by dietary intake of naturally occurring plant sterols. Our aim was to investigate if a high intake of naturally occurring plant sterols is related to a lower risk of contracting a first MI. The analysis included 1005 prospective cases (219 women, 786 men) and 3148 matched referents (723 women, 2425 men), aged 29-73 y at baseline, from the population-based Northern Sweden Health and Disease Study. A food frequency questionnaire (FFQ) was completed at baseline. Absolute plant sterol intake was inversely related to the risk of a first MI in men (OR highest vs. lowest quartile = 0.70; 95% CI: 0.53, 0.85; P-trend = 0.006) but not in women. After adjustment for confounders, the estimated risk was somewhat attenuated (OR highest vs. lowest quartile = 0.71; 95% CI: 0.55, 0.92; P-trend = 0.067), suggesting that increasing sterol intake from 150 to 340 mg/d reduces the risk of a first MI by 29%. Energy-adjusted plant sterol intake was not related to the risk of a first MI in either men or women. In conclusion, the findings of this observational study show that a high absolute intake of naturally occurring plant sterols is significantly related to a lower risk of a first MI in men in northern Sweden, whereas no significant relation was seen for energy-adjusted plant sterol intake. In women, no significant associations were found. The results from this study show that intake of plant sterols may be important in prevention of MI.

  • 243. Klingberg, Sofia
    et al.
    Winkvist, Anna
    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.
    Evaluation of plant sterol intake estimated with the Northern Sweden FFQ2013In: Public Health Nutrition, ISSN 1368-9800, E-ISSN 1475-2727, Vol. 16, no 3, p. 460-467Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate plant sterol intake estimated with the eighty-four-item Northern Sweden FFQ against repeated 24 h dietary recalls (24-HDR) as the reference method. Design: Randomly recruited participants from the Vasterbotten Intervention Programme (VIP) responded to an FFQ (FFQ1). Over the subsequent 12 months, ten repeated 24-HDR were carried out. After this, a second FFQ (FFQ2) was completed. Setting: Vasterbotten county, northern Sweden. Subjects: Ninety-six men and ninety-nine women. Results: The Pearson correlation coefficient for absolute total plant sterol intake estimated with FFQ1 and 24-HDR was 0.58 and 0.55 for the men and women, respectively. Cross-classification of participants into quartiles of absolute plant sterol intake estimated with FFQ1 and 24-HDR showed that 90% of the men and 83% of the women were classified into the same or an adjacent quartile. For energy-adjusted plant sterol intake, 71% of the men and 74% of the women were classified into the same or an adjacent quartile. The agreement for cross-classification of participants into quartiles between FFQ1 and FFQ2 was good for both absolute and energy-adjusted plant sterol intake. Conclusions: The FFQ is able to capture absolute plant sterol intake to the same extent as other nutrients, and to rank individuals according to both their absolute and energy-adjusted plant sterol intake. The reproducibility of the FFQ was good, suggesting that the method is reliable. This makes it possible to use plant sterol data from the FFQ in large-scale studies of the association between plant sterol intake and disease.

  • 244. Knekt, Paul
    et al.
    Ritz, John
    Pereira, Mark A
    O'Reilly, Eilis J
    Augustsson, Katarina
    Fraser, Gary E
    Goldbourt, Uri
    Heitmann, Berit L
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Liu, Simin
    Pietinen, Pirjo
    Spiegelman, Donna
    Stevens, June
    Virtamo, Jarmo
    Willett, Walter C
    Rimm, Eric B
    Ascherio, Alberto
    Antioxidant vitamins and coronary heart disease risk: a pooled analysis of 9 cohorts.2004In: American Journal of Clinical Nutrition, ISSN 0002-9165, Vol. 80, no 6, p. 1508-20Article in journal (Refereed)
  • 245. Koivula, R. W.
    et al.
    Grontved, A.
    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.
    Ostergaard, L.
    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.
    Renstrom, Frida
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Bicycling to work and primordial prevention of cardiovascular and type 2 diabetes risk: a cohort study from Northern Sweden2016In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, p. S150-S150, article id 298Article in journal (Refereed)
  • 246.
    Kokkonen, Heidi
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Mullazehi, Mohammed
    Division of Clinical Immunology, Uppsala University, 751 85 Uppsala, Sweden.
    Berglin, Ewa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    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.
    Rönnelid, Johan
    Division of Clinical Immunology, Uppsala University, 751 85 Uppsala, Sweden.
    Rantapää Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Antibodies of IgG, IgA and IgM isotypes against cyclic citrullinated peptide precede the development of rheumatoid arthritis2011In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 13, no 1, p. R13-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: We and others have previously shown that antibodies against cyclic citrullinated proteins (anti-CCP) precede the development of rheumatoid arthritis (RA) and in a more recent study we reported that individuals who subsequently developed RA had increased concentrations of several cytokines and chemokines years before the onset of symptoms of joint disease. Here we aimed to evaluate the prevalence and predictive values of anti-CCP antibodies of IgG, IgM and IgA isotype in individuals who subsequently developed RA and also to relate these to cytokines and chemokines, smoking, genetic factors and radiographic score.

    METHODS: A case-control study (1:4 ratio) was nested within the Medical Biobank and the Maternity cohorts of Northern Sweden. Patients with RA were identified from blood donors predating the onset of disease by years. Matched controls were selected randomly from the same registers. IgG, IgA and IgM anti-CCP2 antibodies were determined using EliA anti-CCP assay on ImmunoCAP 250 (Phadia AB, Uppsala, Sweden).

    RESULTS: Of 86 patients with RA identified as blood donors prior to the onset of symptoms, samples were available from 71 for analyses. The median (Q1 to Q3) predating time was 2.5 years (1.1 to 5.9 years). The sensitivity of anti-CCP antibodies in the pre-patient samples was 35.2% for IgG, 23.9% for IgA, and 11.8% for IgM. The presence of IgG and IgA anti-CCP antibodies was highly significant compared with controls. IgG and IgA anti-CCP2 predicted RA significantly in conditional logistic regression models odds ratio (OR) = 94.1, 95% confidence interval (CI) 12.7 to 695.4 and OR = 11.1, 95% CI 4.4 to 28.1, respectively, the IgM anti-CCP showed borderline significance OR = 2.5 95% CI 0.9 to 6.3. Concentrations of all anti-CCP isotypes increased the closer to the onset of symptoms the samples were collected with an earlier and higher increase for IgG and IgA compared with IgM anti-CCP. IgA and IgG anti-CCP positive individuals had different patterns of up-regulated chemokines and also, smoking brought forward the appearance of IgA anti-CCP antibodies in pre-RA individuals.

    CONCLUSIONS: Anti-CCP2 antibodies of both the IgG and IgA isotypes pre-dated the onset of RA by years; also, both IgG and IgA anti-CCP2 antibodies predicted the development of RA, with the highest predictive value for IgG anti-CCP2 antibodies.

  • 247.
    Kokkonen, Heidi
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Söderström, Ingegerd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lejon, Kristina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Rantapää Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Up-regulation of cytokines and chemokines predates the onset of rheumatoid arthritis2010In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 62, no 2, p. 383-391Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To identify whether cytokines, cytokine-related factors, and chemokines are up-regulated prior to the development of rheumatoid arthritis (RA).

    METHODS: A nested case-control study was performed in 86 individuals who had donated blood samples before experiencing any symptoms of disease (pre-patients) and 256 matched control subjects (1:3 ratio). In 69 of the pre-patients, blood samples were also obtained at the time of the diagnosis of RA. The plasma levels of 30 cytokines, related factors, and chemokines were measured using a multiplex system.

    RESULTS: The levels of several of the cytokines, cytokine receptors, and chemokines were significantly increased in individuals before disease onset compared with the levels in control subjects; i.e., those representing signs of general immune activation (interleukin-1beta [IL-1beta], IL-2, IL-6, IL-1 receptor antagonist, and tumor necrosis factor), activation of Th1 cells (interferon-gamma, IL-12), Th2 cells (IL-4, eotaxin), Treg cells (IL-10), bone marrow-derived factors (IL-7, granulocyte-macrophage colony-stimulating factor, and granulocyte colony-stimulating factor), as well as chemokines (monocyte chemotactic protein 1 and macrophage inflammatory protein 1alpha). The levels were particularly increased in anti-cyclic citrullinated peptide antibody- and rheumatoid factor-positive individuals, and the concentration of most of these increased further after disease onset. The concentration of IL-17 in individuals before disease onset was significantly higher than that in patients after disease onset. Individuals in whom RA subsequently developed were discriminated from control subjects mainly by the presence of Th1 cells, Th2 cells, and Treg cell-related cytokines, while chemokines, stromal cell-derived cytokines, and angiogenic-related markers separated patients after the development of RA from individuals before the onset of RA.

    CONCLUSION: Individuals in whom RA later developed had significantly increased levels of several cytokines, cytokine-related factors, and chemokines representing the adaptive immune system (Th1, Th2, and Treg cell-related factors); after disease onset, the involvement and activation of the immune system was more general and widespread.

  • 248. Korodi, Zoltan
    et al.
    Dillner, Joakim
    Jellum, Egil
    Lumme, Sonja
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Thoresen, Steinar
    Hakulinen, Timo
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Urologi och andrologi.
    Luostarinen, Tapio
    Lehtinen, Matti
    Hakama, Matti
    Human papillomavirus 16, 18, and 33 infections and risk of prostate cancer: a Nordic nested case-control study.2005In: Cancer Epidemiology Biomarkers & Prevention, ISSN 1055-9965, Vol. 14, no 12, p. 2952-5Article in journal (Refereed)
  • 249.
    Krachler, Benno
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Trends in food intakes in Swedish adults 1986-1999: findings from the Northern Sweden MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) Study.2005In: Public Health Nutrition, ISSN 1368-9800, E-ISSN 1475-2727, Vol. 8, no 6, p. 628-635Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To determine changes in reported food frequency in adults between 1986 and 1999. DESIGN: Four consecutive cross-sectional surveys. SETTING: Counties of Norrbotten and Västerbotten, Northern Sweden. SUBJECTS: The Northern Sweden MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) population, four independent cross-sectional surveys in 1986, 1990, 1994 and 1999. Randomly selected age-stratified samples of the population aged 25-64 years. Analysis is based on 2982 males and 3087 females who completed an 84-item food-frequency questionnaire. RESULTS: Between 1986 and 1999, average reported consumption of 3%-fat milk decreased from 42 to 7 intakes month(-1) in men and from 28 to 4 intakes month(-1) in women. Reported use of 1.5%-fat milk increased from 6 to 27 intakes month(-1) in men and from 6 to 24 in women. Monthly intakes of potatoes and root vegetables decreased from 38 to 27 in men and from 39 to 32 in women. Consumption of pasta increased from 4 to 7 intakes month(-1) in both sexes. Intakes of solid fats with 80% fat content dropped from 92 to 62 per month in men and from 78 to 52 per month in women, whereas use of 40%-fat spread increased from 12 to 22 intakes month(-1) in men and from 5 to 26 in women. Monthly intakes of vegetable oil increased from 3 to 12 in men and from 3 to 15 in women. The percentage of overweight or obese individuals (body mass index >25 kg m(-2)) increased from 52 to 65% in men and from 41 to 52% in women (P for linear trend in all these changes, <0.001). CONCLUSIONS: Our data indicate reduced consumption of foods with a high content of saturated fats. In spite of that, there is an unbroken trend towards increased obesity.

  • 250.
    Krachler, Benno
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Population-wide changes in reported lifestyle are associated with redistribution of adipose tissue.2009In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 37, no 5, p. 545-553Article in journal (Refereed)
2345678 201 - 250 of 510
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