title: Polymorphisms in genes related to one-carbon metabolism are not related to pancreatic cancer in PanScan and PanC4.
abstract: OBJECTIVE
  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: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK. M.Leenders-6@umcutrecht.nl
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mesh_terms: D002244:Carbon / Q000378:metabolism*; D016022:Case-Control Studies; D015331:Cohort Studies; D018095:Germ-Line Mutation; D006801:Humans; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D014481:United States / Q000453:epidemiology
chemical_list: D002244:Carbon