Selected polymorphisms of DNA repair genes and risk of pancreatic cancer

Cancer Detect Prev. 2006;30(3):284-91. doi: 10.1016/j.cdp.2006.05.002. Epub 2006 Jul 17.


Background: Genetic variants of DNA repair genes may contribute to pancreatic carcinogenesis. O(6)-methylguanine-DNA methyltransferase (MGMT) is the major protein that removes alkylating DNA adducts, and apurinic/apyrimidinic endonuclease 1 (APE1) and X-ray repair cross-complementing group 1 (XRCC1) play important roles in the base excision repair pathway.

Methods: We investigated the association between polymorphisms of MGMT (Leu(84)Phe and Ile(143)Val), APE1 (Asp(148)Glu), and XRCC1 (Arg(194)Trp and Arg(399)Gln) and risk of pancreatic cancer in a case-control study. Exposure information from 384 patients with primary pancreatic ductal adenocarcinoma and 357 cancer-free healthy controls were collected and genomic DNAs were genotyped for five markers. Controls were frequency matched to patients by age at enrollment (+/-5 years), gender, and race. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) by using unconditional logistic regression models.

Results: There was no significant main effect or interaction with smoking of these genetic variants on the risk of pancreatic cancer. However, the XRCC1(194) polymorphism had a significant interaction with the APE1(148) (p=0.005) or MGMT(84) polymorphism (p=0.02) in modifying the risk of pancreatic cancer.

Conclusions: This study suggests that polymorphisms of genes involved in the repair of alkylating DNA adduct and DNA base damage may play a role in modulating the risk of pancreatic cancer. Larger studies are required to validate these preliminary findings. The mechanism of the combined genotype effects remains to be elucidated.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • DNA Repair / genetics*
  • Environment
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • O(6)-Methylguanine-DNA Methyltransferase / genetics
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide
  • Risk
  • Smoking


  • O(6)-Methylguanine-DNA Methyltransferase