XRCC2 and XRCC3 gene polymorphism and risk of pancreatic cancer. Am J Gastroenterol 2008 Feb;103(2):360-7
Date
11/08/2007Pubmed ID
17986315Pubmed Central ID
PMC2268638DOI
10.1111/j.1572-0241.2007.01615.xScopus ID
2-s2.0-39049114078 (requires institutional sign-in at Scopus site) 67 CitationsAbstract
OBJECTIVES: XRCC2 and XRCC3 are key components of the homologous recombination (HR) machinery that repairs DNA double-strand breaks. We hypothesized that the altered HR repair capacity conferred by single nucleotide polymorphisms (SNPs) would modify individual susceptibility to sporadic pancreatic cancer.
METHODS: In a hospital-based case-control study, genomic DNA and exposure information was obtained from 468 patients with pathologically confirmed pancreatic adenocarcinoma and 498 frequency-matched healthy controls at M.D. Anderson Cancer Center during January 2000 to September 2006. Genotypes of XRCC2 31479 G>A (Arg188His) and XRCC3 17893 A>G and 18067 C>T (Thr241Met) were determined using the Masscode technology. Unconditional logistic regression models were used to estimate the odds ratio (OR) and its 95% confidence interval (CI) in non-Hispanic whites (408 cases and 449 controls).
RESULTS: The distribution of genotype frequencies was not different between cases and controls. We observed a significant effect modification between XRCC2 polymorphism and smoking status and pack-year of smoking in modifying pancreatic cancer risk (P value for interaction 0.02 and 0.05, respectively). Compared with never-smokers carrying the XRCC2 Arg188Arg genotype, the OR (95% CI) for individuals carrying the (188)His allele was 2.32 (1.25-4.31) among ever-smokers, 1.43 (0.59-3.48) among light smokers (< or = 22 pack-years), and 3.42 (1.47-7.96) among heavy smokers (> or =22 pack-years). The two XRCC3 SNPs are in strong linkage disequilibrium, but there was no suggestive association between XRCC3 genotype and the risk of pancreatic cancer.
CONCLUSION: XRCC2 Arg188His polymorphism may be one of the genetic modifiers for smoking-related pancreatic cancer.
Author List
Jiao L, Hassan MM, Bondy ML, Wolff RA, Evans DB, Abbruzzese JL, Li DAuthor
Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AgedCase-Control Studies
DNA-Binding Proteins
Female
Humans
Male
Middle Aged
Pancreatic Neoplasms
Polymorphism, Single Nucleotide
Risk Factors
Smoking
