Susceptibility to lung cancer and genetic polymorphisms in the alcohol metabolite-related enzymes alcohol dehydrogenase 3, aldehyde dehydrogenase 2, and cytochrome P450 2E1 in the Japanese population

BACKGROUND. it is believed that acetaldehyde plays an important role in alcohol-related carcinogenesis; although current epidemiologic studies have provided inconsistent findings on the association between alcohol consumption and the risk of lung cancer. METHODS. To clarify the hypothesis that genetic polymorphisms in alcohol-metabolizing enzymes may influence susceptibility to lung cancer, the authors conducted a hospital-based case-control study and examined genetic polymorphisms in the alcohol dehydrogenase 3, aldehyde dehydrogenase 2 (ALDH(2)), and cytochrome P450 2131 genes in 505 patients with histologically confirmed lung cancer and in a group of 256 noncancer controls who provided complete cigarette and alcohol consumption histories. Genotyping was conducted by polymerase chain reaction-restriction fragment-length polymorphism assay. RESULTS. A significant association was noted between alcohol consumption and lung cancer risk. Thus, using the median value for the controls as the cut-off point, the odds ratios (OR) for light and heavy drinkers were 1.76 and 1.95, respectively (P for trend =.012), compared with nondrinkers. In addition, there was a significant trend toward increased risk of lung cancer in drinkers with ALDH2 variant alleles (P for trend <.0001). The adjusted OR for heavy drinkers was 6.15 compared with nondrinkers. Regarding associations between histologic type and genotypes, the ALDH(2) variant allele was significantly less common in patients who had adenocarcinoma compared with controls. CONCLUSIONS. The current observations suggested a positive association between alcohol consumption and the risk of lung cancer: Drinking may increase the risk, especially among individuals who have the variant ALDH(2) alleles.