Polymorphisms in genes related to one-carbon metabolism are not related to pancreatic cancer in PanScan and PanC4

Max Leenders, Samsiddhi Bhattacharjee, Paolo Vineis, Victoria Stevens, H. Bas Bueno-De-Mesquita, Xiao Ou Shu, Laufey Amundadottir, Myron Gross, Geoffrey S. Tobias, Jean Wactawski-Wende, Alan A. Arslan, Eric J. Duell, Charles S. Fuchs, Steven Gallinger, Patricia Hartge, Robert N. Hoover, Elizabeth A. Holly, Eric J. Jacobs, Alison P. Klein, Charles KooperbergAndrea Lacroix, Donghui Li, Margaret T. Mandelson, Sara H. Olson, Gloria Petersen, Harvey A. Risch, Kai Yu, Brian M. Wolpin, Wei Zheng, Ilir Agalliu, Demetrius Albanes, Marie Christine Boutron-Ruault, Paige M. Bracci, Julie E. Buring, Federico Canzian, Kenneth Chang, Stephen J. Chanock, Michelle Cotterchio, J. Michael Gaziano, Edward L. Giovanucci, Michael Goggins, Göran Hallmans, Susan E. Hankinson, Judith A. Hoffman-Bolton, David J. Hunter, Amy Hutchinson, Kevin B. Jacobs, Mazda Jenab, Kay Tee Khaw, Peter Kraft, Vittorio Krogh, Robert C. Kurtz, Robert R. McWilliams, Julie B. Mendelsohn, Alpa V. Patel, Kari G. Rabe, Elio Riboli, Anne Tjønneland, Dimitrios Trichopoulos, Jarmo Virtamo, Kala Visvanathan, Joanne W. Elena, Herbert Yu, Anne Zeleniuch-Jacquotte, Rachael Z. Stolzenberg-Solomon

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)595-602
Number of pages8
JournalCancer Causes and Control
Volume24
Issue number3
DOIs
StatePublished - Mar 2013

Keywords

  • Biomarkers
  • Epidemiology
  • One-carbon metabolism
  • Pancreatic cancer
  • Polymorphisms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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