Journal Article

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

Wen-Yi Huang, Yu-Tang Gao, Asif Rashid, Lori C. Sakoda, Jie Deng, Ming-Chang Shen, Bin-Sheng Wang, Tian-Quan Han, Bai-He Zhang, Bingshu E. Chen, Philip S. Rosenberg, Stephen J. Chanock and Ann W. Hsing

in Carcinogenesis

Volume 29, issue 1, pages 100-105
Published in print January 2008 | ISSN: 0143-3334
Published online November 2007 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgm247
Selected base excision repair gene polymorphisms and susceptibility to biliary tract cancer and biliary stones: a population-based case–control study in China

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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 and R399Q, 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 the XRCC1 194RR genotype, those with the WW genotype had a 1.9-fold risk of bile duct cancer [odds ratio (OR) = 1.9, 95% confidence interval (CI) = 1.1–3.5, Ptrend= 0.03], and compared with subjects carrying the XRCC1 280RR genotype, those with the XRCC1 280H allele had a 50% reduced risk of bile duct cancer (OR = 0.5, 95% CI = 0.3–0.9, Ptrend = 0.05). The effect of the R280H polymorphism persisted (Ptrend= 0.03), when all three XRCC1 polymorphisms were jointly considered in the model, a finding supported by the haplotype results (covariate-adjusted global permutation P = 0.03). We also found an inverse association between the APEX1 148E allele and gallbladder stones (Ptrend = 0.03), but no association for the OGG1 polymorphism. This study suggests that genetic variants in XRCC1 and APEX1 may alter susceptibility to biliary tract cancer and stones. Further studies are required to confirm the reported associations.

Journal Article.  4440 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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