Abstract
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.
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This study was funded by the open project of State Key Laboratory of Molecular Oncology (SKL-KF-2013-03), National Natural Science Foundation of China (31271382 & 81201586), Beijing Natural Science Foundation (5122020), Beijing Higher Education Young Elite Teacher Project (YETP0521), Beijing City Talent Training Project (2012D009016000002), and Program for Changjiang Scholars and Innovative Research Team in University (IRT13045).
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Haiyong Wang, Lei Tong, and Jinyu Wei contributed equally to this work.
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Wang, H., Tong, L., Wei, J. et al. The ALDH7A1 genetic polymorphisms contribute to development of esophageal squamous cell carcinoma. Tumor Biol. 35, 12665–12670 (2014). https://doi.org/10.1007/s13277-014-2590-9
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DOI: https://doi.org/10.1007/s13277-014-2590-9