Clinical significance of ALDH2 rs671 polymorphism in esophageal cancer: evidence from 31 case-control studies

Abstract

Tingting Zhao,1* Chun Wang,1* Lili Shen,1* Dongying Gu,1 Zhi Xu,1 Xunlei Zhang,2 Yong Xu,1 Jinfei Chen1 1Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 2Department of Oncology, Nantong Tumor Hospital, Nantong University, Nantong, People’s Republic of China *These authors contributed equally to this work Background: Aldehyde dehydrogenase 2 (ALDH2), a critical enzyme for the detoxification of alcohol, is associated with many types of cancers. To verify the relationship of ALDH2 rs671 G>A polymorphism and esophageal cancer (EC), we performed a meta-analysis of a total of 31 published data including 8,510 patients and 16,197 controls. Methods: The pooled odds ratio (OR) and the 95% confidence interval (CI) were calculated using a fixed or random-effects model. Heterogeneity (PH), publication bias, and sensitivity analysis were also determined. Results: Although a protective effort was found in the rs671 homozygote comparison (AA/GG: OR=0.69; 95% CI=0.48–0.98), the heterozygote comparison was apparently associated with the risk of EC, particularly in the Chinese population (AG/GG: OR=1.39; 95% CI=1.03–1.87). Alcohol consumption remarkably increased this risk, especially in the AG genotype. Drinking men with the AG genotype appeared to show a higher risk (AG/GG: OR=4.39; 95% CI=1.24–6.55) than drinking women. Conclusion: The present meta-analysis provided advanced information regarding the association of the ALDH2 A>G polymorphism and EC. Taken together, insights from this study suggested an enhanced effect on the development of EC through a genetic–environmental interaction. Keywords: aldehyde dehydrogenase-2, single nucleotide polymorphism, SNP, esophageal cancer, EC, meta-analysis