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 and residential area was carried out in Taixing city of Jiangsu province, China. Blood samples were collected and tested for ADH2 and ALDH2 genotypes by PCR-RFLP method.


RESULTS
There were no significant differences in the frequency of either ADH2 or ALDH2 genotypes between cases and controls. Compared with no-drinkers possessing ALDH21*1 genotypes, drinkers with ALDH21*2 or ALDH22*2 genotypes and cumulative amount of 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*1 and 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 or ALDH22*2 genotypes. Drinkers with cumulative amount of alcohol consumption >3 (Kg * years) who possessed both inactive ALDH2 (ALDH21*2 or ALDH22*2) and inactive ADH (ADH21*2 or ADH22*2) genotypes were not at a significantly higher risk of HCC (adjusted OR=4.26, 95%CI: 0.63-29.08) compared to no-drinkers possessing ADH21*1 and ALDH21*1 genotypes. Compared with individuals possessing ALDH21*1, with negative HBsAg and cumulative amount of alcohol consumption <or=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 risk of HCC (OR=49.71, 95%CI: 5.51-448.96).


CONCLUSIONS
These results revealed that it was not ADH2 but ALDH2 polymorphisms 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 genotypes should be encouraged to reduce their consumption of alcoholic beverages.
Ding
Jianhua
J
Division of Epidemiology, Cancer Research Institute of Jiangsu Province, Nanjing 210009, China. djh_200@126.com
Li
Suping
S
Wu
Jianzhong
J
Gao
Changming
C
Zhou
Jiannong
J
Cao
Haixia
H
Su
Ping Su
PS
Liu
Yanting
Y
Zhou
Xuefu
X
Chang
Jun
J
D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D044466:Asian People / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial