PURPOSE: The evidence of a relation between folate intake and one-carbon metabolism (OCM) with pancreatic cancer (PanCa) is inconsistent. In this study, the association between genes and single-nucleotide polymorphisms (SNPs) related to OCM and PanCa was assessed. METHODS: Using biochemical knowledge of the OCM pathway, we identified thirty-seven genes and 834 SNPs to examine in association with PanCa. Our study included 1,408 cases and 1,463 controls nested within twelve cohorts (PanScan). The ten SNPs and five genes with lowest p values (<0.02) were followed up in 2,323 cases and 2,340 controls from eight case-control studies (PanC4) that participated in PanScan2. The correlation of SNPs with metabolite levels was assessed for 649 controls from the European Prospective Investigation into Cancer and Nutrition. RESULTS: When both stages were combined, we observed suggestive associations with PanCa for rs10887710 (MAT1A) (OR 1.13, 95 %CI 1.04-1.23), rs1552462 (SYT9) (OR 1.27, 95 %CI 1.02-1.59), and rs7074891 (CUBN) (OR 1.91, 95 %CI 1.12-3.26). After correcting for multiple comparisons, no significant associations were observed in either the first or second stage. The three suggested SNPs showed no correlations with one-carbon biomarkers. CONCLUSIONS: This is the largest genetic study to date to examine the relation between germline variations in OCM-related genes polymorphisms and the risk of PanCa. Suggestive evidence for an association between polymorphisms and PanCa was observed among the cohort-nested studies, but this did not replicate in the case-control studies. Our results do not strongly support the hypothesis that genes related to OCM play a role in pancreatic carcinogenesis.
PURPOSE: The evidence of a relation between folate intake and one-carbon metabolism (OCM) with pancreatic cancer (PanCa) is inconsistent. In this study, the association between genes and single-nucleotide polymorphisms (SNPs) related to OCM and PanCa was assessed. METHODS: Using biochemical knowledge of the OCM pathway, we identified thirty-seven genes and 834 SNPs to examine in association with PanCa. Our study included 1,408 cases and 1,463 controls nested within twelve cohorts (PanScan). The ten SNPs and five genes with lowest p values (<0.02) were followed up in 2,323 cases and 2,340 controls from eight case-control studies (PanC4) that participated in PanScan2. The correlation of SNPs with metabolite levels was assessed for 649 controls from the European Prospective Investigation into Cancer and Nutrition. RESULTS: When both stages were combined, we observed suggestive associations with PanCa for rs10887710 (MAT1A) (OR 1.13, 95 %CI 1.04-1.23), rs1552462 (SYT9) (OR 1.27, 95 %CI 1.02-1.59), and rs7074891 (CUBN) (OR 1.91, 95 %CI 1.12-3.26). After correcting for multiple comparisons, no significant associations were observed in either the first or second stage. The three suggested SNPs showed no correlations with one-carbon biomarkers. CONCLUSIONS: This is the largest genetic study to date to examine the relation between germline variations in OCM-related genes polymorphisms and the risk of PanCa. Suggestive evidence for an association between polymorphisms and PanCa was observed among the cohort-nested studies, but this did not replicate in the case-control studies. Our results do not strongly support the hypothesis that genes related to OCM play a role in pancreatic carcinogenesis.
Authors: Brenda Diergaarde; Randall Brand; Janette Lamb; Soo Yeon Cheong; Kim Stello; M Michael Barmada; Eleanor Feingold; David C Whitcomb Journal: Pancreatology Date: 2010-05-17 Impact factor: 3.996
Authors: R Z Stolzenberg-Solomon; P Pietinen; M J Barrett; P R Taylor; J Virtamo; D Albanes Journal: Am J Epidemiol Date: 2001-04-01 Impact factor: 4.897
Authors: D T Silverman; C A Swanson; G Gridley; S Wacholder; R S Greenberg; L M Brown; R B Hayes; G M Swanson; J B Schoenberg; L M Pottern; A G Schwartz; J F Fraumeni; R N Hoover Journal: J Natl Cancer Inst Date: 1998-11-18 Impact factor: 13.506
Authors: Laufey Amundadottir; Peter Kraft; Rachael Z Stolzenberg-Solomon; Charles S Fuchs; Gloria M Petersen; Alan A Arslan; H Bas Bueno-de-Mesquita; Myron Gross; Kathy Helzlsouer; Eric J Jacobs; Andrea LaCroix; Wei Zheng; Demetrius Albanes; William Bamlet; Christine D Berg; Franco Berrino; Sheila Bingham; Julie E Buring; Paige M Bracci; Federico Canzian; Françoise Clavel-Chapelon; Sandra Clipp; Michelle Cotterchio; Mariza de Andrade; Eric J Duell; John W Fox; Steven Gallinger; J Michael Gaziano; Edward L Giovannucci; Michael Goggins; Carlos A González; Göran Hallmans; Susan E Hankinson; Manal Hassan; Elizabeth A Holly; David J Hunter; Amy Hutchinson; Rebecca Jackson; Kevin B Jacobs; Mazda Jenab; Rudolf Kaaks; Alison P Klein; Charles Kooperberg; Robert C Kurtz; Donghui Li; Shannon M Lynch; Margaret Mandelson; Robert R McWilliams; Julie B Mendelsohn; Dominique S Michaud; Sara H Olson; Kim Overvad; Alpa V Patel; Petra H M Peeters; Aleksandar Rajkovic; Elio Riboli; Harvey A Risch; Xiao-Ou Shu; Gilles Thomas; Geoffrey S Tobias; Dimitrios Trichopoulos; Stephen K Van Den Eeden; Jarmo Virtamo; Jean Wactawski-Wende; Brian M Wolpin; Herbert Yu; Kai Yu; Anne Zeleniuch-Jacquotte; Stephen J Chanock; Patricia Hartge; Robert N Hoover Journal: Nat Genet Date: 2009-08-02 Impact factor: 38.330
Authors: András P Keszei; Bas A J Verhage; Mirjam M Heinen; Royle A Goldbohm; Piet A van den Brandt Journal: Cancer Epidemiol Biomarkers Prev Date: 2009-06 Impact factor: 4.254
Authors: Gloria M Petersen; Laufey Amundadottir; Charles S Fuchs; Peter Kraft; Rachael Z Stolzenberg-Solomon; Kevin B Jacobs; Alan A Arslan; H Bas Bueno-de-Mesquita; Steven Gallinger; Myron Gross; Kathy Helzlsouer; Elizabeth A Holly; Eric J Jacobs; Alison P Klein; Andrea LaCroix; Donghui Li; Margaret T Mandelson; Sara H Olson; Harvey A Risch; Wei Zheng; Demetrius Albanes; William R Bamlet; Christine D Berg; Marie-Christine Boutron-Ruault; Julie E Buring; Paige M Bracci; Federico Canzian; Sandra Clipp; Michelle Cotterchio; Mariza de Andrade; Eric J Duell; J Michael Gaziano; Edward L Giovannucci; Michael Goggins; Göran Hallmans; Susan E Hankinson; Manal Hassan; Barbara Howard; David J Hunter; Amy Hutchinson; Mazda Jenab; Rudolf Kaaks; Charles Kooperberg; Vittorio Krogh; Robert C Kurtz; Shannon M Lynch; Robert R McWilliams; Julie B Mendelsohn; Dominique S Michaud; Hemang Parikh; Alpa V Patel; Petra H M Peeters; Aleksandar Rajkovic; Elio Riboli; Laudina Rodriguez; Daniela Seminara; Xiao-Ou Shu; Gilles Thomas; Anne Tjønneland; Geoffrey S Tobias; Dimitrios Trichopoulos; Stephen K Van Den Eeden; Jarmo Virtamo; Jean Wactawski-Wende; Zhaoming Wang; Brian M Wolpin; Herbert Yu; Kai Yu; Anne Zeleniuch-Jacquotte; Joseph F Fraumeni; Robert N Hoover; Patricia Hartge; Stephen J Chanock Journal: Nat Genet Date: 2010-01-24 Impact factor: 38.330