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Title: Polymorphisms in genes related to one-carbon metabolism are not related to pancreatic cancer in PanScan and PanC4
Author: 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.
Keywords: Càncer de pàncrees
Polimorfisme genètic
Pancreas cancer
Genetic polymorphisms
Issue Date: Mar-2013
Publisher: Springer
Abstract: 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. 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. 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. 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.
Note: Versió postprint del document publicat a:
It is part of: Cancer Causes & Control, 2013, vol. 24, num. 3, p. 595-602
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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