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

Cancer Causes Control 2013 Mar 19;24(3):595-602. Epub 2013 Jan 19.

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK.

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.

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http://dx.doi.org/10.1007/s10552-012-0138-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4127987PMC
March 2013
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References

(Supplied by CrossRef)
Article in Oncogene
M Ehrlich et al.
Oncogene 2002
Article in Annu Rev Nutr
AS Tibbetts et al.
Annu Rev Nutr 2010
Article in Adv Genet
JJ Liu et al.
Adv Genet 2010
Article in JAMA
SC Larsson et al.
JAMA 2010
Article in Cancer Causes Control
D-H Kim et al.
Cancer Causes Control 2010
Article in Cancer Epidemiol Biomarkers Prev
SM Collin et al.
Cancer Epidemiol Biomarkers Prev 2010
Article in J Natl Cancer Inst
SC Larsson et al.
J Natl Cancer Inst 2007
Article in J Nutr Biochem
YI Kim et al.
J Nutr Biochem 1999
Article in Am J Epidemiol
PA Baghurst et al.
Am J Epidemiol 1991
Article in Ann Oncol
F Bravi et al.
Ann Oncol 2011
Article in Cancer Causes Control
Z Gong et al.
Cancer Causes Control 2009

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