Relationship between genetic polymorphisms of ALDH2 and ADH1B and esophageal cancer risk: a meta-analysis.

AIM

To evaluate the contribution of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) polymorphisms to the risk of esophageal cancer.

METHODS

Nineteen articles were included by searching MEDLINE, EMBASE and the Chinese Biomedical Database, 13 on ADH1B and 18 on ALDH2. We performed a meta-analysis of case-control studies including 13 studies on ADH1B (cases/controls: 2390/7100) and 18 studies on ALDH2 (2631/6030).

RESULTS

The crude odds ratio [OR (95% confidence interval)] was 2.91 (2.04-4.14) for ADH1B*1/1 (vs ADH1B2/2) and 1.32 (1.17-1.49) for ADH1B1/2. The crude OR for ALDH21/2 (vs ALDH21/1) was 2.52 (1.76-3.61). ADH1B1/1 increased the risk of esophageal cancer among never/rare [1.56 (0.93-2.61)], moderate [2.71 (1.37-5.35)], and heavy drinkers [3.22 (2.27-4.57)]. ADH1B1/2 was associated with a modest risk among moderate drinkers [1.43 (1.09-1.87)]. ALDH21/2 increased the risk among never/rare [1.28 (0.91-1.80)], moderate [3.12 (1.95-5.01)], and heavy [7.12 (4.67-10.86)] drinkers, and among ex-drinkers [5.64 (1.57-20.25)]. ALDH22/2 increased the risk among drinkers [4.42 (1.72-11.36)]. ADH1B1/1 plus ALDH21/2 was associated with the highest risk for heavy drinkers [12.45 (2.9-53.46)]. The results of the meta-regression analysis showed that the effects of ADH1B1/1 and ALDH21/2 increased with the level of alcohol consumption. ALDH21/2 was associated with a high risk among Taiwan Chinese and Japanese drinkers, as opposed to a moderate risk among drinkers in high-incidence regions of Mainland China. ADH1B1/1 in heavy drinkers and ALDH21/*2 in moderate-to-heavy drinkers was associated with similarly high risk among both men and women.

CONCLUSION

ADH1B/ALDH2 genotypes affect the risk of esophageal cancer, and the risk is modified by alcohol consumption, ethnicity, and gender.