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Base excision repair (BER) corrects DNA damage caused by oxidative stress and chronic inflammation, putative risk factors for cancer. To understand the relationship between genetic variation in BER genes and risk of biliary tract cancer and biliary stones, we examined non-synonymous polymorphisms in three key BER genes—x-ray repair cross-complementing group 1 (XRCC1) (R194W, rs1799782;R280H, rs25489 andR399Q, rs25487), apurinic/apyrimidinic endonuclease (APEX1) (D148E, rs3136820) and 8-oxoguanine DNA glycosylase (OGG1) (S326C, rs1052133), in a population-based study of 411 biliary tract cancer cases (237 gallbladder, 127 bile duct and 47 ampulla of Vater), 891 biliary (gallbladder or bile duct) stone cases and 786 population controls conducted in Shanghai, China. Compared with subjects carrying theXRCC1 194RRgenotype, those with theWWgenotype had a 1.9-fold risk of bile duct cancer [odds ratio (OR) = 1.9, 95% confidence interval (CI) = 1.1–3.5,P  trend = 0.03], and compared with subjects carrying theXRCC1 280RRgenotype, those with theXRCC1 280Hallele had a 50% reduced risk of bile duct cancer (OR = 0.5, 95% CI = 0.3–0.9,P  trend = 0.05). The effect of theR280Hpolymorphism persisted (P  trend = 0.03), when all threeXRCC1polymorphisms were jointly considered in the model, a finding supported by the haplotype results (covariate-adjusted global permutationP = 0.03). We also found an inverse association between theAPEX1 148Eallele and gallbladder stones (P  trend= 0.03), but no association for theOGG1polymorphism. This study suggests that genetic variants inXRCC1andAPEX1may alter susceptibility to biliary tract cancer and stones. Further studies are required to confirm the reported associations.

carcinogenesis

Selected base excision repair gene polymorphisms and susceptibility to biliary tract cancer and biliary stones: a population-based case–control study in China