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Carcinogenesis Advance Access originally published online on November 4, 2007
Carcinogenesis 2008 29(1):100-105; doi:10.1093/carcin/bgm247
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Published by Oxford University Press 2007.

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 Huang1,*, Yu-Tang Gao2, Asif Rashid3, Lori C. Sakoda4, Jie Deng2, Ming-Chang Shen5, Bin-Sheng Wang6, Tian-Quan Han7, Bai-He Zhang8, Bingshu E. Chen1, Philip S. Rosenberg1, Stephen J. Chanock1,9 and Ann W. Hsing1

1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA
2 Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China
3 Department of Pathology, MD Anderson Cancer Center, Houston, TX77030, USA
4 Department of Epidemiology, University of Washington, Seattle, WA 98198, USA
5 Shanghai Tumor Hospital
6 Zhongshan Hospital, Fudan University, Shanghai, China
7 Ruijin Hospital, Shanghai Second Medical University, Shanghai, China
8 Oriental Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
9 Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA

* To whom correspondence should be addressed. Tel: +1 301 435 4710; Fax: +1 301 402 1819; Email: huangw{at}mail.nih.gov

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.

Abbreviations: APEX1, apurinic/apyrimidinic endonuclease; BER, base excision repair; BMI, body mass index; CI, confidence interval; OGG1, 8-oxoguanine DNA glycosylase; OR, odds ratio; SNP, single-nucleotide polymorphism; XRCC1, x-ray repair cross-complementing group 1

Received September 13, 2007; revised October 24, 2007; accepted October 30, 2007.


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