Alcohol Dehydrogenase-2 and Aldehyde Dehydrogenase-2 Genotypes, Alcohol Drinking and the Risk of Primary Hepatocellular Carcinoma in a Chinese Population

Objective: To investigate the relationship of alcohol dehydrogenase-2 (ADH2) and aldehyde dehydrogenase-2 (ALDH2) genotypes as well as alcohol drinking to the susceptibility of primary hepatocellular carcinoma(HCC).
Methods: A case-control study including 208 cases of HCC and 208 controls matched with sex, age andresidential area was carried out in Taixing city of Jiangsu province, China. Blood samples were collected andtested for ADH2 and ALDH2 genotypes by PCR-RFLP method.
Results: There were no significant differencesin the frequency of either ADH2 or ALDH2 genotypes between cases and controls. Compared with no-drinkerspossessing ALDH21*1 genotypes, drinkers with ALDH21*2 or ALDH22*2 genotypes and cumulative amountof alcohol consumption >3 (Kg * years) were at a significantly higher risk of developing HCC (OR=3.30, 95%CI:1.24-8.83). In contrast, there was no significant difference in cancer risk between no-drinkers with ADH21*1and drinkers with ADH2 1*2 or ADH22*2 genotypes. A dose-dependent positive result was found (P=0.044)between cumulative amount of alcohol consumption and the risk of HCC in individuals carrying ALDH21*2 orALDH22*2 genotypes. Drinkers with cumulative amount of alcohol consumption >3 (Kg * years) who possessedboth inactive ALDH2 (ALDH21*2 or ALDH22*2) and inactive ADH (ADH21*2 or ADH22*2) genotypes werenot at a significantly higher risk of HCC (adjusted OR=4.26, 95%CI: 0.63-29.08) compared to no-drinkerspossessing ADH21*1 and ALDH21*1 genotypes. Compared with individuals possessing ALDH21*1, with negativeHBsAg and cumulative amount of alcohol consumption ≤3 (Kg * years), those with ALDH21*2 or ALDH22*2,positive HBsAg, and cumulative amount of alcohol consumption >3 (Kg * years) had a significantly higher riskof HCC (OR=49.71, 95%CI: 5.51–448.96).
Conclusion: These results revealed that it was not ADH2 but ALDH2polymorphisms that had a significant interaction with heavy alcohol consumption in the development of HCC.This result suggests that to help lower their risk for HCC , persons with ALDH21*2 or ALDH22*2 genotypesshould be encouraged to reduce their consumption of alcoholic beverages.