Genetic polymorphisms of alcohol metabolising enzymes: their role in susceptibility to oesophageal cancer
Genetic polymorphisms of alcohol metabolising enzymes: their role in susceptibility to oesophageal cancer
复制标题
DOI：
10.1515/cclm.2008.073
复制
发表时间：
2008-01-01
影响因子：
6.8
通讯作者：
Parker, M. Iqbal
中科院分区：
文献类型：
--
作者：
Li, Dong-Ping;Dandara, Collet;Parker, M. Iqbal
背景：酒精是南非人群食管癌易感性的主要危险因素。酒精代谢酶、乙醇脱氢酶（ADH）和乙醛脱氢酶（ALDH 2）多态性在该人群食管癌易感性中的作用尚不清楚。酒精代谢酶表现出多态性，导致变异等位基因的增加或减少activity.Methods：这些多态性的作用，在食管癌的风险增加进行了调查，在238例患者和268名对照，从黑人和混合黑人南非，使用PCR/RFLP技术。在黑人受试者中，ADH 3 *2/*2基因型与食管癌风险增加显著相关（比值比，2.19; p = 0.004）。低活性ALDH 2 *2等位基因与黑人食管癌风险增加显著相关（比值比，2.35; p = 0.0084）。据观察，ADH变体ADH 2 *1和ADH 3 *2与食管癌风险增加相关，这可能是由于这些等位基因的携带者与具有高活性等位基因的携带者相比对酒精消耗的耐受性（ADH 2 *2和ADH 2 *3），其与令人不快的乙醛中间体的较高产生相关。
Background: Alcohol is a major risk factor for susceptibility to oesophageal cancer in the South African population. The role of polymorphisms in alcohol metabolising enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH2) in predisposition of this population to oesophageal cancer is unknown. Alcohol metabolising enzymes exhibit polymorphisms that result in variant alleles with either increased or decreased activity.Methods: The role of these polymorphisms in increased risk of oesophageal cancer was investigated in 238 patients and 268 controls from Black and Mixed Ancestry South Africans, using the PCR/RFLP technique.Results: The ADH3*2/*2 genotype was significantly associated with increased risk for oesophageal cancer amongst Black subjects (odds ratio, 2.19; p = 0.004). The low activity ALDH2*2 allele was significantly associated with increased risk for oesophageal cancer amongst the Black subjects (odds ratio, 2.35; p = 0.0084).Conclusions: It was observed that ADH variants, ADH2*1 and ADH3*2, were associated with increased risk for oesophageal cancer, possibly due to the tolerance of the carriers of these alleles to alcohol consumption compared to those with high activity alleles (ADH2*2 and ADH2*3) which are associated with higher production of the unpleasant acetaldehyde intermediate.