ARTICLE ABSTRACT
Background: The role of polymorphisms on ADH1B and ALDH2 in patients with chronic hepatitis B is unclear. This study aims to examine whether alcohol drinking mediates the association between two ADH1B and ALDH2 polymorphisms and the risk of hepatocellular carcinoma among chronic hepatitis B patients.Methods: A total of 3,824 individuals were enrolled in this study. Two SNPs, rs1229984 (ADH1B) and rs671 (ALDH2), were genotyped using the Affymetrix Axiom Genome-Wide CHB1 Array (Affymetrix, Inc). Multivariate unconditional logistic regression and mediation analyses were used, comparing CT or TT with CC for rs1229984 and GA and AA with GG for rs671.Results: There were 602 cases of hepatocellular carcinoma and 3,222 controls. Frequencies of the rs1229984 (ADH1B) T allele and rs671 (ALDH2) A allele were 72.9% and 28.8%, respectively. Individuals who carried at least one deficient allele for both SNPs were significantly less likely to become habitual alcohol drinkers, with an OR and 95% confidence interval (CI) of 0.24 (0.15–0.40). Alleles for rs1229984 (ADH1B) and rs671 (ALDH2) were not associated with hepatocellular carcinoma in multivariate analyses. However, mediation analyses showed that the rs1229984 T allele, rs671 A allele, and two SNPs combined were significantly associated with decreased hepatocellular carcinoma risk, mediated through alcohol drinking, with an OR (95% CI) of 0.87 (0.79–0.96), 0.70 (0.61–0.82), and 0.73 (0.58–0.88), respectively.Conclusions: Polymorphisms on ADH1B and ALDH2 had significant indirect effects on hepatocellular carcinoma risk, mediated through alcohol drinking.Impact: Future genetic studies of chronic hepatitis B and hepatocellular carcinoma must take mediation effects into consideration. Cancer Epidemiol Biomarkers Prev; 25(4); 693–9. ©2016 AACR.
