Wang Haiyong, Tong Lei, Wei Jinyu, Pan Wenting, Li Lichao, Ge Yunxia, Zhou Liqing, Yuan Qipeng, Zhou Changchun, Yang Ming
State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, P. O. Box 53, Beijing, 100029, China.
Tumour Biol. 2014 Dec;35(12):12665-70. doi: 10.1007/s13277-014-2590-9. Epub 2014 Sep 12.
Although the entire etiology of esophageal squamous cell carcinoma (ESCC) is still unclear, alcohol drinking has been identified as a major environmental risk factor. The aldehyde dehydrogenase (ALDH) superfamily members are major enzymes involved in the alcohol-metabolizing pathways. Accumulating evidences demonstrated that ALDH7A1, one of ALDH superfamily members, degrades and detoxifies acetaldehyde generated by alcohol metabolism and have been associated with development and prognosis of multiple cancers. However, it is still unknown if ALDH7A1 single nucleotide polymorphisms (SNPs) contribute to ESCC susceptibility. In this study, we examined the association between sixteen ALDH7A1 SNPs and risk of developing ESCC. Genotypes were determined in 2,098 ESCC patients and 2,150 controls (three independent hospital-based case-control sets from different regions of China). Odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated by logistic regression. Our data demonstrated that only the ALDH7A1 rs13182402 SNP confer susceptibility to ESCC (For AG genotype, OR = 0.75, 95 % CI = 0.66-0.91, P = 4.8 × 10(-6); for GG genotype, OR = 0.59, 95 % CI = 0.41-0.88, P = 0.003). These results are consistent to the biological functions of ALDH7A1 during alcohol metabolism and carcinogenesis.
尽管食管鳞状细胞癌（ESCC）的整体病因仍不清楚，但饮酒已被确定为主要的环境风险因素。醛脱氢酶（ALDH）超家族成员是参与酒精代谢途径的主要酶。越来越多的证据表明，ALDH超家族成员之一的ALDH7A1可降解并解毒酒精代谢产生的乙醛，并与多种癌症的发生和预后相关。然而，ALDH7A1单核苷酸多态性（SNP）是否会导致ESCC易感性仍不清楚。在本研究中，我们检测了16个ALDH7A1 SNP与ESCC发病风险之间的关联。在中国不同地区的2098例ESCC患者和2150例对照（三个独立的基于医院的病例对照数据集）中确定了基因型。通过逻辑回归估计比值比（OR）和95%置信区间（CI）。我们的数据表明，只有ALDH7A1 rs13182402 SNP会导致ESCC易感性（对于AG基因型，OR = 0.75，95%CI = 0.66 - 0.91，P = 4.8×10^(-6)；对于GG基因型，OR = 0.59，95%CI = 0.41 - 0.88，P = 0.003）。这些结果与ALDH7A1在酒精代谢和致癌过程中的生物学功能一致。
