Polymorphisms of alcohol- and smoking-related susceptibility genes and risk of esophageal cancer

Abstract

Epidemiological studies have shown that esophageal cancer is associated with alcohol drinking and with smoking. There are several genes involved in both tobacco and alcohol pathways that modulate the susceptibility for esophageal cancer. Our objectives were to: (i) confirm the effect of smoking and alcohol drinking patterns on the risk of esophageal cancer, (ii) assess the independent effects of polymorphisms of ALDH2, CYP2E1, NQO1, XRCC1, and TP53 (alias p53) on risk of the disease, and (iii) explore the possible multigenetic effects and gene-environmental interaction. We conducted a population-based case–control study with 220 incident cases of esophageal cancer and 415 healthy controls in Taixing City, China, from March 1, 2000, to August 31, 2000. Epidemiological data were collected by face-to-face interview. Genotypes of ALDH2, CYP2E1, NQO1, XRCC1, and TP53 were assayed with polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) techniques. No obvious association with the risk for esophageal cancer was found for polymorphisms of the CYP2E1 and TP53 genes. The odds ratios were 1.89 (95% CI = 0.9–3.7) for ALDH2 22 genotype, 2.60 (95% CI = 1.6–4.3) for NQO1 CT and TT, and 1.68 (95% CI = 1.1–2.6) for XRCC1 399 GG and GA after adjustment for age, sex, education level, body mass index, alcohol drinking, and smoking. The adjusted combined odds ratio of ALDH2 22 genotype and drinking often or every day was 4.37 (95% CI = 0.9–21.2), compared with those who never or occasionally drink and have ALDH2 11 or 12 genotypes. The adjusted combined odds ratio of ALDH2 22 and ever smoking was 5.89 (95% CI = 1.9–17.6), compared with those who never smoke and have ALDH2 11 and 12 genotypes. Our results also suggest that there may be potential interaction between NQO1 and smoking, as well as alcohol drinking. Our results suggest that ALDH2, NQO1, and XRCC1 polymorphisms may alter the susceptibility to esophageal cancer, and that gene polymorphisms may also modulate the effects of smoking and drinking on esophageal cancer risk in a Chinese population.