XRCC2 and XRCC3 gene polymorphism and risk of pancreatic cancer.
OBJECTIVE
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.


CONCLUSIONS
XRCC2 Arg188His polymorphism may be one of the genetic modifiers for smoking-related pancreatic cancer.
Jiao
Li
L
Department of Gastrointestinal Medical Oncology, The University of Texas M D Anderson Cancer Center, houston, TX 77030, USA.
Hassan
Manal M
MM
Bondy
Melissa L
ML
Wolff
Robert A
RA
Evans
Douglas B
DB
Abbruzzese
James L
JL
Li
Donghui
D
D000368:Aged; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
D004268:DNA-Binding Proteins; C110901:X-ray repair cross complementing protein 3; C113187:XRCC2 protein, human