Alcohol Consumption and Lung Cancer According to Ile349Val Polymorphism in ADH3 Gene: Beyond the Tobacco Smoking Effect.

Objectives: Smoking is the leading cause of lung cancer. However, several studies have suggested other factors such as alcohol consumption could also play a role through polymorphisms associated with alcohol metabolism. We investigated the association between alcohol consumption and lung cancer according to the Ile349Val polymorphism in the alcohol dehydrogenase 3 ADH3 gene. Methods: We carried out a hospital-based case-control study, a total of 402 incident cases of lung cancer and 383 controls were genotyped for the Ile349Val polymorphism by polymerase chain reaction combined with restriction fragment length polymorphism. Alcohol consumption and other variables were measured using questionnaires in personal interviews. We used multiple logistic regressions to estimate adjusted odd ratios using and 95% confidence intervals. Results: In multivariate analysis, an increased risk of lung cancer was observed for the highest category of alcohol consumption (≥30 g/day), although it does not reach statistical significance (OR=1.60, 95% CI: 0.91-2.83). Besides, an increased risk of lung cancer was observed in the highest category of alcohol consumption for the Ile/Val genotype compared with the Ile/Ile genotype (OR=2.35, 95% CI: 1.04-5.33). Conclusions: This study suggests that beyond smoking consumption, a high consumption of alcohol might increase the risk of lung cancer. No clear association was found between alcohol consumption and lung cancer according to the Ile349Val polymorphism in ADH3 gene.

Association of p21 Ser31Arg and p53 Arg72Pro polymorphisms with lung cancer risk in CAPUA study.

BACKGROUND: The aim of this study was to investigate how Ser31Arg polymorphisms in p21 may modify lung cancer susceptibility. Because p21 is the major downstream mediator of p53, we analyzed the combined effect of two polymorphisms, p21 Ser31Arg and TP53 Arg72Pro, to elucidate whether polymorphic variants determine the risk of lung cancer. METHODS: This was designed as a hospital-based case-control study, and included 675 cases and 675 control subjects matched by ethnicity, gender, and age. Genotypes were determined by polymerase chain reaction restriction fragment length polymorphism, and multivariate unconditional logistic regression was performed to analyze the results. RESULTS: Subjects who carried the p21 Ser31Arg allele had a higher risk of lung cancer (adjusted odds ratio [OR] 1.38; 95% confidence interval [CI] 0.99-2.03). This risk was increased in men aged younger than 55 years (adjusted OR 2.35; 95% CI 1.00-5.51). Smokers had an increased risk of lung cancer (adjusted OR 2.23; 95% CI 1.24-4.02). Men younger than 55 years carrying risk alleles for both genes (p21 Ser31Arg and TP53 Arg72Pro) had an increased risk (adjusted OR 5.78; 95% CI 1.38-24.19), as did smokers with both risk alleles (adjusted OR 4.52; 95% CI 1.52-13.50). CONCLUSION: The presence of both variant alleles increased the risk of developing lung cancer in men, particularly in smokers younger than 55 years.