科研之友
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摘要
AIM: To evaluate the association between genetic polymorphisms in CYP2E1, ALDH2 and ADH1B and the risk of esophageal squamous cell carcinoma (ESCC) in a high risk area of Gansu province, in Chinese males.
METHODS: A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYP2E1*c1c2, ALDH2*12 and ADH1B *11 genotypes). A total of 80 esophageal cancer cases and 480 controls were recruited.
RESULTS: Compared with controls, cases had a greater prevalence of heavier alcohol consumption (53.8% vs 16.2%) and a higher proportion of alcohol drinkers with > 30 drink-years (28.8% vs 13.5%). Heavier alcohol consumption and alcohol drinking with > 30 drink-years increased the risk of ESCC, with ORs (95% CI) of 3.20 (1.32-9.65) and 1.68 (0.96-3.21). CYP2E1 (*c1c1), ALDH2 (*12) and ADH1B (*11) genotype frequencies were higher among patients with squamous cell carcinomas, at a level close to statistical significance (P = 0.014; P = 0.094; P = 0.0001 respectively). There were synergistic interactions among alcohol drinking and ALDH2, ADH1B and CYP2E1 genotypes. The risk of the ESCC in moderate-to-heavy drinkers with an inactive ALDH2 encoded by ALDH2*12 as well as ADH1B encoded by ADH1B *11 and CYP2EI encoded by CYP2EI *c1c1 was higher than that in the never/rare-to-light drinkers with an active ALDH2 (*11 genotype) as well as ADH1B (*12 + *22) and CYP2E1 (*c1c2 + *c2c2) genotypes, with a statistically significant difference; ORs (95% CI) of 8.58 (3.28-22.68), 27.12 (8.52-70.19) and 7.64 (2.82-11.31) respectively. The risk of the ESCC in moderate-to-heavy drinkers with ALDH2 (*12) combined the ADH1B (*11) genotype or ALDH2 (*12) combined the CYP2E1 (*c1c1) genotype leads to synergistic interactions, higher than drinkers with ALDH2 (*11) + ADH1B (*12 + *22), ALDH2 (*11) + CYP2E1 (*c1c2 + *c2c2) respectively, ORs (95% CI) of 7.46 (3.28-18.32) and 6.82 (1.44-9.76) respectively. Individuals with the ADH1B combined the CYP2E1 genotype showed no synergistic interaction.
CONCLUSION: In our study, we found that alcohol consumption and polymorphisms in the CYP2E1, ADH1B and ALDH2 genes are important risk factors for ESCC, and that there was a synergistic interaction among polymorphisms in the CYP2E1, ALDH2 and ADH1B genes and heavy alcohol drinking, in Chinese males living in Gansu province, China.
