TY - JOUR A1 - Zheng, Ju-Sheng A1 - Luan, Jian'an A1 - Sofianopoulou, Eleni A1 - Imamura, Fumiaki A1 - Stewart, Isobel D. A1 - Day, Felix R. A1 - Pietzner, Maik A1 - Wheeler, Eleanor A1 - Lotta, Luca A. A1 - Gundersen, Thomas E. A1 - Amiano, Pilar A1 - Ardanaz, Eva A1 - Chirlaque, Maria-Dolores A1 - Fagherazzi, Guy A1 - Franks, Paul W. A1 - Kaaks, Rudolf A1 - Laouali, Nasser A1 - Mancini, Francesca Romana A1 - Nilsson, Peter M. A1 - Onland-Moret, N. Charlotte A1 - Olsen, Anja A1 - Overvad, Kim A1 - Panico, Salvatore A1 - Palli, Domenico A1 - Ricceri, Fulvio A1 - Rolandsson, Olov A1 - Spijkerman, Annemieke M. W. A1 - Sanchez, Maria-Jose A1 - Schulze, Matthias Bernd A1 - Sala, Nuria A1 - Sieri, Sabina A1 - Tjonneland, Anne A1 - Tumino, Rosario A1 - van der Schouw, Yvonne T. A1 - Weiderpass, Elisabete A1 - Riboli, Elio A1 - Danesh, John A1 - Butterworth, Adam S. A1 - Sharp, Stephen J. A1 - Langenberg, Claudia A1 - Forouhi, Nita G. A1 - Wareham, Nicholas J. T1 - Plasma vitamin C and type 2 diabetes BT - genome-wide association study and Mendelian randomization analysis in European populations JF - Diabetes care N2 - OBJECTIVE: Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants. RESULTS: We identified 11 genomic regions associated with plasma vitamin C (P < 5 x 10(-8)), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF, GSTA5, RGS14, AKT1, and FADS1. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding FADS1 variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10). CONCLUSIONS: These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention. Y1 - 2020 U6 - https://doi.org/10.2337/dc20-1328 SN - 0149-5992 SN - 1935-5548 VL - 44 IS - 1 SP - 98 EP - 106 PB - American Diabetes Association CY - Alexandria ER - TY - JOUR A1 - Kroeger, Janine A1 - Meidtner, Karina A1 - Stefan, Norbert A1 - Guevara, Marcela A1 - Kerrison, Nicola D. A1 - Ardanaz, Eva A1 - Aune, Dagfinn A1 - Boeing, Heiner A1 - Dorronsoro, Miren A1 - Dow, Courtney A1 - Fagherazzi, Guy A1 - Franks, Paul W. A1 - Freisling, Heinz A1 - Gunter, Marc J. A1 - Maria Huerta, Jose A1 - Kaaks, Rudolf A1 - Key, Timothy J. A1 - Khaw, Kay Tee A1 - Krogh, Vittorio A1 - Kuehn, Tilman A1 - Mancini, Francesca Romana A1 - Mattiello, Amalia A1 - Nilsson, Peter M. A1 - Olsen, Anja A1 - Overvad, Kim A1 - Palli, Domenico A1 - Ramon Quiros, J. A1 - Rolandsson, Olov A1 - Sacerdote, Carlotta A1 - Sala, Nuria A1 - Salamanca-Fernandez, Elena A1 - Sluijs, Ivonne A1 - Spijkerman, Annemieke M. W. A1 - Tjonneland, Anne A1 - Tsilidis, Konstantinos K. A1 - Tumino, Rosario A1 - van der Schouw, Yvonne T. A1 - Forouhi, Nita G. A1 - Sharp, Stephen J. A1 - Langenberg, Claudia A1 - Riboli, Elio A1 - Schulze, Matthias Bernd A1 - Wareham, Nicholas J. T1 - Circulating Fetuin-A and Risk of Type 2 Diabetes BT - a mendelian randomization analysis JF - Diabetes : a journal of the American Diabetes Association N2 - Fetuin-A, a hepatic-origin protein, is strongly positively associated with risk of type 2 diabetes in human observational studies, but it is unknown whether this association is causal. Weaimed to study the potential causal relation of circulating fetuin-A to risk of type 2 diabetes in a Mendelian randomization study with single nucleotide polymorphisms located in the fetuin-A-encoding AHSG gene. We used data from eight European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study including 10,020 incident cases. Plasma fetuin-A concentration was measured in a subset of 965 subcohort participants and 654 case subjects. A genetic score of the AHSG single nucleotide polymorphisms was strongly associated with fetuin-A (28% explained variation). Using the genetic score as instrumental variable of fetuin-A, we observed no significant association of a 50 mu g/mL higher fetuin-A concentration with diabetes risk (hazard ratio 1.02 [95% CI 0.97, 1.07]). Combining our results with those from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (12,171 case subjects) also did not suggest a clear significant relation of fetuin-A with diabetes risk. In conclusion, although there is mechanistic evidence for an effect of fetuin-A on insulin sensitivity and secretion, this study does not support a strong, relevant relationship between circulating fetuin-A and diabetes risk in the general population. Y1 - 2018 U6 - https://doi.org/10.2337/db17-1268 SN - 0012-1797 SN - 1939-327X VL - 67 IS - 6 SP - 1200 EP - 1205 PB - American Diabetes Association CY - Alexandria ER - TY - JOUR A1 - Christakoudi, Sofia A1 - Pagoni, Panagiota A1 - Ferrari, Pietro A1 - Cross, Amanda J. A1 - Tzoulaki, Ioanna A1 - Muller, David C. A1 - Weiderpass, Elisabete A1 - Freisling, Heinz A1 - Murphy, Neil A1 - Dossus, Laure A1 - Turzanski Fortner, Renee A1 - Agudo, Antonio A1 - Overvad, Kim A1 - Perez-Cornago, Aurora A1 - Key, Timothy J. A1 - Brennan, Paul A1 - Johansson, Mattias A1 - Tjonneland, Anne A1 - Halkjaer, Jytte A1 - Boutron-Ruault, Marie-Christine A1 - Artaud, Fanny A1 - Severi, Gianluca A1 - Kaaks, Rudolf A1 - Schulze, Matthias Bernd A1 - Bergmann, Manuela M. A1 - Masala, Giovanna A1 - Grioni, Sara A1 - Simeon, Vittorio A1 - Tumino, Rosario A1 - Sacerdote, Carlotta A1 - Skeie, Guri A1 - Rylander, Charlotta A1 - Borch, Kristin Benjaminsen A1 - Quiros, J. Ramon A1 - Rodriguez-Barranco, Miguel A1 - Chirlaque, Maria-Dolores A1 - Ardanaz, Eva A1 - Amiano, Pilar A1 - Drake, Isabel A1 - Stocks, Tanja A1 - Häggström, Christel A1 - Harlid, Sophia A1 - Ellingjord-Dale, Merete A1 - Riboli, Elio A1 - Tsilidis, Konstantinos K. T1 - Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort JF - International journal of cancer N2 - Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (+/- 0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood. KW - BMI change KW - cancer KW - middle adulthood KW - weight gain KW - weight loss Y1 - 2020 U6 - https://doi.org/10.1002/ijc.33339 SN - 0020-7136 SN - 1097-0215 VL - 148 IS - 7 SP - 1637 EP - 1651 PB - Wiley CY - Hoboken ER - TY - GEN A1 - Christakoudi, Sofia A1 - Pagoni, Panagiota A1 - Ferrari, Pietro A1 - Cross, Amanda J. A1 - Tzoulaki, Ioanna A1 - Muller, David C. A1 - Weiderpass, Elisabete A1 - Freisling, Heinz A1 - Murphy, Neil A1 - Dossus, Laure A1 - Turzanski Fortner, Renee A1 - Agudo, Antonio A1 - Overvad, Kim A1 - Perez-Cornago, Aurora A1 - Key, Timothy J. A1 - Brennan, Paul A1 - Johansson, Mattias A1 - Tjonneland, Anne A1 - Halkjaer, Jytte A1 - Boutron-Ruault, Marie-Christine A1 - Artaud, Fanny A1 - Severi, Gianluca A1 - Kaaks, Rudolf A1 - Schulze, Matthias Bernd A1 - Bergmann, Manuela M. A1 - Masala, Giovanna A1 - Grioni, Sara A1 - Simeon, Vittorio A1 - Tumino, Rosario A1 - Sacerdote, Carlotta A1 - Skeie, Guri A1 - Rylander, Charlotta A1 - Borch, Kristin Benjaminsen A1 - Quiros, J. Ramon A1 - Rodriguez-Barranco, Miguel A1 - Chirlaque, Maria-Dolores A1 - Ardanaz, Eva A1 - Amiano, Pilar A1 - Drake, Isabel A1 - Stocks, Tanja A1 - Haggstrom, Christel A1 - Harlid, Sophia A1 - Ellingjord-Dale, Merete A1 - Riboli, Elio A1 - Tsilidis, Konstantinos K. T1 - Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (+/- 0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1373 KW - BMI change KW - cancer KW - middle adulthood KW - weight gain KW - weight loss Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-573609 SN - 1866-8372 IS - 7 ER -