title: Association of cytokine and DNA repair gene polymorphisms with hepatitis B-related hepatocellular carcinoma.
abstract: BACKGROUND
  Hepatitis B virus (HBV) induces hepatocellular carcinoma (HCC) mainly by causing chronic necroinflammatory hepatic disease. We investigated the mechanisms underlying the inflammatory hepatocarcinogenesis by examining whether genetic variations in cytokines, antioxidant enzymes, and DNA repair genes affect the HCC risk.
  
  
  METHODS
  We analyzed 10 polymorphisms in the genes for interleukin-1beta (IL-1B), interleukin-1-receptor antagonist (IL-1RN), tumor necrosis factor-alpha (TNF-A), glutathione S-transferase, XRCC1, hMLH1, and XPD in 577 HBV carriers with HCC and 389 HBV carrier controls.
  
  
  RESULTS
  Overall, only the hMLH1-93*A allele significantly increased HCC risk. We identified polymorphism combinations associated with HCC. In the presence of the IL-1RN*2 allele, adjusted odds ratios (ORs) for HCC associated with C/C, T/C, and T/T genotypes of the IL-1B-31 polymorphism were 1.00, 2.93 [95% confidence interval (95% CI) 1.07-8.07], and 5.76 (95% CI 1.79-18.53), respectively. There was a dose-dependent association between the number of putative high-risk genotypes in the IL-1B, TNF-A, hMLH1, and XRCC1 genes and HCC. The adjusted OR for HBV carriers with > or = 3 putative high-risk genotypes was 9.29 (95% CI 2.90-29.75) compared with those with none or only one of the high-risk genotypes. These associations were not observed among HBV carriers without the IL-1RN*2 allele. Smoking modified the combined effect of multiple loci in the IL-1RN, IL-1B, TNF-A, hMLH1, and XRCC1 genes; a high-risk multilocus genotype only significantly increased the risk in smokers (adjusted OR 4.84; 95% CI 1.69-13.92).
  
  
  CONCLUSIONS
  Genetic variations in cytokine and DNA repair genes contribute to susceptibility to HBV-related HCC. Smoking increased such genetic susceptibility.
authors.affiliation: Department of Family Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Chun-Chieh
authors.initials: CC
authors.lastname: Chen
authors.forename: Shi-Yi
authors.initials: SY
authors.lastname: Yang
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Liu
authors.forename: Chih-Lin
authors.initials: CL
authors.lastname: Lin
authors.forename: Yun-Fan
authors.initials: YF
authors.lastname: Liaw
authors.forename: Shi-Ming
authors.initials: SM
authors.lastname: Lin
authors.forename: Shou-Dong
authors.initials: SD
authors.lastname: Lee
authors.forename: Pei-Jer
authors.initials: PJ
authors.lastname: Chen
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
authors.forename: Ming-Whei
authors.initials: MW
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000821:virology*; D002353:Carrier State; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012907:Smoking / Q000009:adverse effects
chemical_list: D016207:Cytokines