MTHFR Gene Polymorphisms are Not Involved in Pancreatic Cancer Risk: A Meta-analysis

  • Tu, Yu-Liang (Department of Hepatobiliary Surgery, the First Affiliated Hostpial of PLA General Hospital) ;
  • Wang, Shi-Bin (Department of General Surgery, the First Affiliated Hostpial of PLA General Hospital) ;
  • Tan, Xiang-Long (Department of Hepatobiliary Surgery, the First Affiliated Hostpial of PLA General Hospital)
  • Published : 2012.09.30


Purpose: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been reported to be associated with pancreatic cancer, but the published studies have yielded inconsistent results. This study assessed the relationship between MTHFR gene polymorphisms and the risk for pancreatic cancer using a meta-analysis approach. Methods:A search of Google scholar, PubMed, Cochrane Library and CNKI databases before April 2012 was performed, and then associations of the MTHFR polymorphisms with pancreatic cancer risk were summarized. The association was assessed by odds ratios (ORs) with 95% confidence intervals (CIs). Publication bias was also calculated. Results: Four relative studies on MTHFR gene polymorphisms (C667T and A1298C) were included in this meta-analysis. Overall, C667T (TT vs. CC:OR=1.61,95%CI=0.78-3.34; TT vs. CT: OR=1.41,95%CI=0.88-2.25; Dominant model:OR=0.68,95%CI=0.40-1.17; Recessive model: OR=0.82,95%CI=0.52-1.30) and A1298C (CC vs. AA:OR=1.01,95%CI=0.47-2.17; CC vs. AC: OR=0.99,95%CI=0.46-2.14; Dominant model:OR=1.01, 95%CI=0.47-2.20; Recessive model: OR=1.01,95%CI=0.80-1.26) did not increase pancreatic cancer risk. Conclusions: This meta-analysis indicated that MTHFR polymorphisms (C667T and A1298C) are not associated with pancreatic cancer risk.


  1. Boccia S, Hung R, Ricciardi G, et al (2008). Meta- and Pooled Analyses of the Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms and Gastric Cancer Risk: A Huge-GSEC Review. Am J Epidemiol, 167, 505-16.
  2. Botto LD, Yang Q (2000). 5, 10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am J Epidemiol, 151, 862-77.
  3. Danes BS, Lynch HT (1982). A familial aggregation of pancreatic cancer: an in vitro study. JAMA, 247, 2798-802.
  4. Lynch HT, Fitzsimmons ML, Smyrk TC, et al (1990). Familial pancreatic cancer: clinicopathologic study of 18 nuclear families. Am J Gastroenetrol, 85, 54-60.
  5. Eads CA, Nickel AE, Laird PW (2002). Complete genetic suppression of polyp formation and reduction of CpG-island hypermethylation in Apc(Min/+) Dnmt1-hypomorphic Mice. Cancer Res, 62, 1296-9.
  6. Frosst P, Blom HJ, Milos R, et al (1995). A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet, 10, 111-3.
  7. Ghadirian P, Boyle P, Simard, et al (1991). Reported family aggregation of pancreatic cancer within a population based case-control study in the Francophone community in Montreal, Canada. Int J Pancreatol, 10, 183-96.
  8. Heijmans BT, Boer JM, Suchiman HE, et al (2003). A common variant of the methylenetetrahydrofolate reductase gene (1p36) is associated with an increased risk of cancer. Cancer Res, 63, 1249-53.
  9. Kono S, Chen K (2005). Genetic polymorphisms of methylenetetrahydrofolate reductase and colorectal cancer and adenoma. Cancer Sci, 96, 535-42.
  10. Li DH, Ahmed M, Li Y, et al (2005). 5, 10-methylenetetrahydrofolate reductase polymorphisms and the risk of pancreatic cancer. Cancer Epidemiol Biomarkers Prev, 14, 1470-6.
  11. Matsubayashi H, Skinner HG, Iacobuzio-Donahue C, et al (2005). Pancreaticobiliary cancers with deficient methylenetetrahydrofolate reductase genotypes. Clin Gastroenterol Hepatol, 3, 752-60.
  12. National Cancer Institute, Surveillance Epidemiology and End Results. Pancreas. SEER Stat Fact Sheets. Availble from: URL:
  13. Sanjoaquin MA, Allen N, Couto E, et al (2005). Folate intake and colorectal cancer risk: a meta-analytical approach. Int J Cancer, 113, 825-8.
  14. Stolzenberg-Solomon RZ, Albanes D, Nieto FJ, et al (1999). Pancreatic cancer risk and nutrition-related methyl-group availability indicators in male smokers. J Natl Cancer Inst, 91, 535-41.
  15. Stolzenberg-Solomon RZ, Pietinen P, Barrett MJ, et al (2001). Dietary and other methyl-group availability factors and pancreatic cancer risk in a cohort of male smokers. Am J Epidemiol, 153, 680-7.
  16. Suzuki T, Matsuo K, Sawaki A, et al (2008). Alcohol drinking and one-carbon metabolism-related gene polymporphisms on pancreatic cancer risk. Cancer Epidemiol Biomarkers Prev, 17, 2742-7.
  17. Taioli E, Garza MA, Ahn YO, et al (2009). Meta- and pooled analyses of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and colorectal cancer: a HuGE-GSEC review. Am J Epidemiol, 170, 1207-21.
  18. Vimalachandran D, Ghaneh P, Costello E, et al (2004). Genetics and prevention of pancreatic cancer. Cancer Control, 11, 6-14.
  19. Weisberg I, Tran P, Christensen B, et al (1998). A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab, 64, 169-72.

Cited by

  1. The Methylenetetrahydrofolate Reductase C677T Polymorphism and Breast Cancer Risk in Asian Populations vol.15, pp.14, 2014,
  2. Associations between polymorphisms in folate-metabolizing genes and pancreatic cancer risk in Japanese subjects vol.16, pp.1, 2016,
  3. Evaluation of the MTHFR C677T Polymorphism as a Risk Factor for Colorectal Cancer in Asian Populations vol.16, pp.18, 2016,