Esophageal cancer risk by ALDH2 and ADH2 polymorphisms and alcohol consumption: exploration of gene-environment and gene-gene interactions.

Alcohol drinking is a major risk factor for esophageal cancer in Japan and its impact may be modulated by levels of ALDH2, ADH2 and CYP2E1, three representative alcohol-metabolizing enzymes which display genetic polymorphisms altering individual alcohol-oxidizing capacity and drinking behavior. To assess the actual influence of ADH2 Arg47His, ALDH2 Glu487Lys and CYP2E1 variant c2 allele polymorphisms on esophageal cancer risk with conjunction with alcoholic consumption, the present 1:3 matched case-control study was conducted. The 165 histologically diagnosed Japanese esophageal cancer cases were here compared with 495 randomly selected controls, matched with respect to sex and age. Conditional logistic regression was used to calculated Odds Ratios (ORs) and 95% confidence intervals (95% CI). Significant gene-environment interactions between alcohol drinking and both ADH2 and ALDH2 were observed regarding esophageal cancer risk. The ADH2 Arg47His polymorphism showed moderately increased risk (OR for Arg/His and Arg/Arg relative to His/His: 2.01 (1.39-2.90)). In the ALDH2 case, comparing the Glu/Lys with the Glu/Glu genotype, ORs were markedly increased to 9.64 (3.23-28.8) and 95.4 (28.7-317) from 1.88 (0.42-8.37) and 4.62 (0.93-23.1) for moderate drinking and heavy drinking, respectively. No significant alteration in risk was observed with the CYP2E1 polymorphism. In conclusion, the present study revealed a significant gene-environment interaction between alcohol drinking and the ALDH2 polymorphism regarding esophageal cancer risk among a general population in Japan, providing concrete evidence of a role for acetaldehyde in neoplastic development. Interactions between ALDH2 and ADH2 need further clarification.

Risk factors for esophageal cancer: a case-control study in South-western China.

Esophageal cancer is a crucial cancer in China. Yanting in Sichuan Province was a key area with highest esophageal cancer mortality in China, but little evidence on esophageal cancer risk factors has been reported for this area and the etiology remains unclear. To clarify risk factors, a 1:1 matched case-control study was conducted. Totals of 185 eligible esophageal cancer patients and 185 healthy residents matched for sex and age were recruited. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for possible risk/protective factors. All ORs were adjusted by family history of esophageal cancer and occupation, and then further adjusted by other possible confounding factors. Our results showed that smoking and alcohol drinking were risk factors for esophageal cancer with dose-response. The ORs (95% CI) compared with never smokers and drinkers were 4.06 (1.55-10.6) and 2.49 (1.06-5.85), respectively. The OR was further increased to 8.86 (95% CI, 3.82-20.5) for both smoking and drinking in combination. Eating food rapidly (OR=5.84, 95% CI, 2.05-16.7), drinking shallow ground water (OR=4.18, 95% CI, 1.30-13.4) and frequent intake of picked vegetables (OR=2.12, 95% CI, 1.00-4.49) appeared to increase the risk, while frequent intake of fresh fruit (OR=0.42, 95% CI, 0.19-0.89), fresh vegetables (OR= 0.62, 95% CI, 0.32-1.17) and eggs (OR=0.59, 95% CI, 0.25-1.39) decreased the risk. In conclusion, smoking and alcohol drinking are common in Yanting and main contributors to esophageal cancer. Consumption of fresh fruit and eggs are not common and high consumption of these two foods as well as fresh vegetables may decrease the risk of esophageal cancer in this area. In addition, drinking shallow ground water and eating food rapidly, as well as frequent intake of pickled vegetables, are also factors increasing the risk.