Alcohol drinking mediates the association between polymorphisms of ADH1B and ALDH2 and hepatitis B related hepatocellular carcinoma
Menée à Taïwan auprès de 3 824 participants et portant sur 602 cas et 3 222 témoins, cette étude évalue l'association entre une consommation d'alcool, deux polymorphismes à simple nucléotide des gènes ADH1B et ALDH2 et le risque de carcinome hépatocellulaire chez des patients atteints d'une hépatite B chronique
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 risk of HCC among chronic hepatitis B patients. Methods: A total of 3824 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. Santa Clara, CA). Multivariate unconditional logistic regression and mediation analyses were used, comparing CT or TT to CC for rs1229984, and GA and AA to GG for rs671. Results: There were 602 cases of HCC, and 3222 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 odds ratio (OR) and [95% confidence interval (CI)] of 0.24 (0.15-0.40)]. Alleles for rs1229984 (ADH1B) and rs671 (ALDH2) were not associated with HCC in multivariate analyses. However, mediation analyses showed that the rs1229984 T allele, rs671 A allele, and two SNPs combined were significantly associated with decreased HCC 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 HCC risk, mediated through alcohol drinking. Impact: Future genetic studies of chronic hepatitis B and HCC must take mediation effects into consideration.