Polymorphisms in genes related to one-carbon metabolism are not related to pancreatic cancer in PanScan and PanC4
Leenders, Max; Bhattacharjee, Samsiddhi; Vineis, Paolo; Stevens, Victoria; Bueno-De-Mesquita, H. Bas; Shu, Xiao Ou; Amundadottir, Laufey; Gross, Myron; Tobias, Geoffrey S.; Wactawski-Wende, Jean; Arslan, Alan A.; Duell, Eric J.; Fuchs, Charles S.; Gallinger, Steven; Hartge, Patricia; Hoover, Robert N.; Holly, Elizabeth A.; Jacobs, Eric J.; Klein, Alison P.; Kooperberg, Charles; Lacroix, Andrea; Li, Donghui; Mandelson, Margaret T.; Olson, Sara H.; Petersen, Gloria; Risch, Harvey A.; Yu, Kai; Wolpin, Brian M.; Zheng, Wei; Agalliu, Ilir; Albanes, Demetrius; Boutron-Ruault, Marie Christine; Bracci, Paige M.; Buring, Julie E.; Canzian, Federico; Chang, Kenneth; Chanock, Stephen J.; Cotterchio, Michelle; Gaziano, J. Michael; Giovanucci, Edward L.; Goggins, Michael; Hallmans, Göran; Hankinson, Susan E.; Hoffman-Bolton, Judith A.; Hunter, David J.; Hutchinson, Amy; Jacobs, Kevin B.; Jenab, Mazda; Khaw, Kay Tee; Kraft, Peter; Krogh, Vittorio; Kurtz, Robert C.; McWilliams, Robert R.; Mendelsohn, Julie B.; Patel, Alpa V.; Rabe, Kari G.; Riboli, Elio; Tjønneland, Anne; Trichopoulos, Dimitrios; Virtamo, Jarmo; Visvanathan, Kala; Elena, Joanne W.; Yu, Herbert; Zeleniuch-Jacquotte, Anne; Stolzenberg-Solomon, Rachael Z.
(2013) Cancer Causes & Control, volume 24, issue 3, pp. 595 - 602
(Article)
Abstract
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
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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.
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Keywords: Pancreatic cancer, One-carbon metabolism, Polymorphisms, Biomarkers, Epidemiology, Oncology, Cancer Research
ISSN: 0957-5243
Publisher: Springer Netherlands
(Peer reviewed)