乙醇和乙醛脱氢酶基因多态与食道癌易感性

Genetic polymorphisms of alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 associated with the susceptibility on esophageal cancer

目的研究乙醇脱氢酶2（ADH2）和乙醛脱氢酶2（ALDH2）基因多态与食道癌易感性。方法对江苏省泰兴市221例食道癌新发病例和191名对照的饮酒习惯等因素进行调查，采用PCR和变性高效液相色谱法（DHPLC）检测ADH2和ALDH2基因型。结果（1）与携带ALDH2G／G基因型者相比，携带ALDH2MA（OR=5．69，95％CI：2．51～12．18）和ALDH2G／A（OR=1．70，95％CI：1．08～2．68）基因型者患食道癌危险性明显增加，以携带ALDH2A／A的饮酒者最为显著（OR=8．63，95％CI：2．07～35．95）。（2）无论是否饮酒，携带不同ADH2基因型者之间患食道癌的风险差异均无统计学意义。（3）携带ALDH2A／A或G／A基因型者，不论同时携带何种ADH2基因型患食道癌的风险均显著增加，且作用效应为ALDH2A／A≥G／A。（4）与同时携带ALDH2G／G和ADH2A／A的不饮酒者相比，同时携带ALDH2G／A或A／A和ADH2G／A或G／G的饮酒者，患食道癌危险眭OR值高达8．36（95％CI：2．98～23．46）。结论饮酒及醇醛脱氢酶基因多态与食道癌的联系主要与ALDH2有关；携带ALDH2A／A和G／A者减少酒精消耗量，有助于降低患食道癌危险牲。

Objective To evaluate the impact of alcohol dehydrogenase-2 （ADH2） and aldehyde dehydrogenase-2 （ALDH2） polymorphisms on the susceptibility of esophageal cancer. Methods A case-control study including 221 cases of esophageal cancer and 191 controls was carried out in Taixing city of Jiangsu province. ADH2 and ALDH2 genotypes were tested by PCR and denaturing high -- performance liquid chromatography （DHPLC）. Results （1） Compared with ALDH2 G/G carriers, ALDH2 A/A （0R----5.69, 95% CI： 2.51-12.18） and ALDH2 G/A （OR= 1.70, 95% CI： 1.08-2.68） carriers showed a significantly elevated risk of developing esophageal cancer, especially among alcohol drinkers with ALDH2 MA （OR=8.63,95%CI： 2.07-35.95）. （2） Statistical relation was not found between ADH2 genotypes and the risk of esophageal cancer, with regard to the status of alcohol consumption. （3） Whether subjects with whatever ADH2 genotype, ALDH2 G/A or A/A carriers was found to have significantly increased the risk of developing esophageal cancer, with ALDH2 A/A carriers appeared having higher esophageal cancer risk than those ALDH2 G/A carriers. （4）Compared those non-drinkers with both ALDH2 G/G and ADH2 A/A , drinkers with ALDH2 G/A or A/A and ADH2 G/A or G/G genotypes showed a significantly elevated risk of developing esophageal cancer （OR=8.36, 95% CI： 2.98-23.46）. Conclusion These results revealed that it was not ADH2 but ALDH2 polymorphisms and drinking alcohol had a significant interaction with the development of esophageal cancer, suggesting that in order to help lowering the risk of esophageal cancer, individuals who are carrying ALDH2 A/A or G/A genotypes should be encouraged to reduce their consumption of alcohols.