ADH1B基因启动子区多态性和结直肠癌易感性关联分析

An association between single nucleotide polymorphisms in the promoter region of alcohol dehydrogenase 1B and the risk of developing colorectal carcinoma in the Chinese Han population

乙醇脱氢酶在酒精代谢中发挥着氧化乙醇的作用.以往的许多研究发现,乙醇脱氢酶家族中的成员乙醇脱氢酶-1B(ADH1B)的蛋白表达量在多种肿瘤组织中呈现下降的趋势.为了探讨中国汉族人群中ADH1B基因启动子区多态性与结直肠癌易感性的关系,本研究在92例结直肠癌患者的癌旁组织中对ADH1B基因转录起始位点上游大小为2444 bp的启动子区进行了一代测序扫描,并结合千人基因组数据库中的208例中国汉族人群数据分析了ADH1B基因启动子区的多态性与结直肠癌易感性之间的关系.本研究组在该区域内共检测到8个多态位点,其中rs3811802位点与结直肠癌的易感性表现出极强的相关性(OR=2.136;95%CI=1.2~3.7;P=0.006).本研究认为,位于ADH1B基因启动子区的多态位点rs3811802是中国汉族人群中结直肠癌的风险位点.

Alcohol dehydrogenase 1B （ADH1B） functions as an oxidase that is involved in the conversion of ethanol to acetaldehyde. Previous studies have shown that ADH1B expression levels are lower in tumor tissues than in adjacent normal tissues in many cancer types. Therefore, the aim of our study was to evaluate the potential association between single nucleotide polymorphisms （SNPs） in the promoter region of ADHIB and the risk of developing colorectal carcinoma （CRC） in the Chinese Han population including 92 CRC patients and 208 controls. The promoter region （-2444 to ＋ 14 bp of transcription start site） was sequenced via Sanger sequencing in 92 non-cancerous tissues adjacent to tumor tissues from patients diagnosed with CRC. Eight SNPs were identified in this region and the allele frequencies were compared with that of the Chinese Han population in the 1000 Genomes Project. There was difference in the allele frequency of rs3811802 between the patients with CRC and healthy controls （P=0.006）. Subjects carrying allele C had a significant 2.136-fold （95% CI=1.2-3.7）increased risk of developing CRC. Therefore, we suggested that the rs3811802 polymorphism in ADH1B is associated with susceptibility to CRC in the Chinese Han population.