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


Authors: Leenders, M.; Bhattacharjee, S.; Vineis, P.; Stevens, V.; Bueno-de-Mesquita, H. B.; Shu, X. O.; Amundadottir, L.; Gross, M.; Tobias, G. S.; Wactawski-Wende, J.; Arslan, A. A.; Duell, E. J.; Fuchs, C. S.; Gallinger, S.; Hartge, P.; Hoover, R. N.; Holly, E. A.; Jacobs, E. J.; Klein, A. P.; Kooperberg, C.; LaCroix, A.; Li, D.; Mandelson, M. T.; Olson, S. H.; Petersen, G.; Risch, H. A.; Yu, K.; Wolpin, B. M.; Zheng, W.; Agalliu, I.; Albanes, D.; Boutron-Ruault, M. C.; Bracci, P. M.; Buring, J. E.; Canzian, F.; Chang, K.; Chanock, S. J.; Cotterchio, M.; Gaziano, J. M.; Giovanucci, E. L.; Goggins, M.; Hallmans, G.; Hankinson, S. E.; Hoffman Bolton, J. A.; Hunter, D. J.; Hutchinson, A.; Jacobs, K. B.; Jenab, M.; Khaw, K. T.; Kraft, P.; Krogh, V.; Kurtz, R. C.; McWilliams, R. R.; Mendelsohn, J. B.; Patel, A. V.; Rabe, K. G.; Riboli, E.; Tjønneland, A.; Trichopoulos, D.; Virtamo, J.; Visvanathan, K.; Elena, J. W.; Yu, H.; Zeleniuch-Jacquotte, A.; Stolzenberg-Solomon, R. Z.
Article Title: Polymorphisms in genes related to one-carbon metabolism are not related to pancreatic cancer in PanScan and PanC4
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. © 2013 Springer Science+Business Media Dordrecht.
Keywords: biomarkers; pancreatic cancer; epidemiology; polymorphisms; one-carbon metabolism
Journal Title: Cancer Causes & Control
Volume: 24
Issue: 3
ISSN: 0957-5243
Publisher: Springer  
Date Published: 2013-03-01
Start Page: 595
End Page: 602
Language: English
DOI: 10.1007/s10552-012-0138-0
PROVIDER: scopus
PUBMED: 23334854
PMCID: PMC4127987
DOI/URL:
Notes: --- - "Export Date: 1 July 2013" - "CODEN: CCCNE" - "Source: Scopus"
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  1. Sara H Olson
    234 Olson
  2. Robert C Kurtz
    196 Kurtz