Polymorphisms in XRCC1 and Glutathione S-Transferase Genes and Hepatitis B–Related Hepatocellular Carcinoma

• Published in: JNCI : Journal of the National Cancer Institute Vol. 95; no. 19; pp. 1485 - 1488
• Main Authors: Yu, Ming-Whei, Yang, Shi-Yi, Pan, I-Jen, Lin, Chih-Lin, Liu, Chun-Jen, Liaw, Yun-Fan, Lin, Shi-Ming, Chen, Pei-Jer, Lee, Shou-Dong, Chen, Chien-Jen
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 01.10.2003; Oxford Publishing Limited (England)
• Subjects: Biological and medical sciences; Cancer; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - virology; Case-Control Studies; DNA Repair; DNA-Binding Proteins - genetics; Gastroenterology. Liver. Pancreas. Abdomen; Genes; Genotype; Glutathione Transferase - genetics; Health risk assessment; Hepatitis; Hepatitis B - complications; Humans; Liver; Liver Neoplasms - genetics; Liver Neoplasms - virology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Odds Ratio; Polymorphism, Genetic; Risk Assessment; Risk Factors; Tropical medicine; Tumors; X-ray Repair Cross Complementing Protein 1; Asia; Taiwan; Human; Genetic variability; Enzyme; Transferases; Hepatic disease; Hepatocellular carcinoma; Genotype; Malignant tumor; Case control study; Carcinogenesis; Epidemiology; Repair gene; Infection; Viral hepatitis B; Double strand break; Gene; Glutathione transferase; Viral disease; DNA; Risk factor; Digestive diseases; Genetics; Public health; Polymorphism
• ISSN: 0027-8874; 1460-2105; 1460-2105
• DOI: 10.1093/jnci/djg051

Chronic infection with hepatitis B virus (HBV) causes DNA damage. An arginine (Arg)-to-glutamine (Gln) polymorphism at codon 399 in the XRCC1 gene is putatively associated with DNA damage. In a case–control study of 577 HBV surface antigen carriers with hepatocellular carcinoma (HCC) and 389 HBV carrier control subjects, we investigated the association between this polymorphism and the risk of HCC and assessed whether this association varied with glutathione S-transferase (GST) status; GSTs are involved in carcinogen metabolism. All statistical tests were two-sided. The XRCC1 Gln allele was associated with a dose-dependent increased risk of early-onset HCC (<50 years) but not with the risk of late-onset HCC (Ptrend = .01). The GSTT1-null genotype alone did not affect risk, but the GSTM1-null genotype was associated with a decreased risk for early-onset HCC. Various combinations of GSTM1 and GSTT1 genotypes differentially modified the association of XRCC1 with HCC (Pinteraction = .005); e.g., for individuals with the GSTT1-null/GSTM1-present genotype, the risk of HCC was greater for those with the Gln/Gln genotype (odds ratio = 8.07, 95% confidence interval = 1.67 to 38.93) than for those with the Arg/Arg genotype. Thus, GST status appears to affect the risk of HCC associated with this XRCC1 polymorphism.