American Association for Cancer Research
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Supplemental Figure 1c from Alcohol Drinking Mediates the Association between Polymorphisms of ADH1B and ALDH2 and Hepatitis B–Related Hepatocellular Carcinoma

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posted on 2023-03-31, 13:44 authored by Jessica Liu, Hwai-I Yang, Mei-Hsuan Lee, Chin-Lan Jen, Hui-Han Hu, Sheng-Nan Lu, Li-Yu Wang, San-Lin You, Yen-Tsung Huang, Chien-Jen Chen

Principal Component Analysis According to drinkers vs. non-drinkers


Department of Health, Taiwan

Bristol-Myers Squibb Co.

Academia Sinica, Taiwan



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.

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