Affiliations: [a] Center of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China | [b] Key Laboratory of Carcinogenesis and Translational Research, Departments of Thoracic Surgery I, Peking University Cancer Hospital and Institute, Beijing, China | [c] Key Laboratory of Carcinogenesis and Translational Research, Departments of Biochemistry and Molecular Biology, Peking University Cancer Hospital and Institute, Beijing, China | [d] Key Laboratory of Carcinogenesis and Translational Research, Departments of Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China
Note: [1] Ruo-Lan Ma and Li Min contributed equally to this work.
Abstract: N-acetyltransferase 2 (NAT2) gene encodes a phase II enzyme taking part in detoxification of aromatic amines. Published studies have demonstrated that N-Acetyltransferase 2 (NAT2) phenotype is a risk factor of various cancers. Many studies have investigated the association between NAT2 phenotype and susceptibility to esophageal cancer but yielded controversial results. To derive a more precise estimation of this association, a meta-analysis was performed. Electronic databases (Pubmed/Medline, ISI Web of Science and China National Knowledge Infrastructure) in English and Chinese were searched. A total of 5 articles including 476 cases and 1,093 controls were included in this meta-analysis. Odds ratio (OR) with 95% confidence interval (95% CI) was used to evaluate intensity of associations. Pooling studies together, NAT2 slow acetylator phenotype was a significant risk factor of esophageal squamous cell cancer (OR=1.35, 95% CI=1.03–1.77, n=5 studies) but not esophageal adenocarcinoma (OR=0.97, 95% CI=0.47–2.04, n=2 studies). There was a significant association between NAT2 acetylator phenotypes and ESCC in South Asian populations (OR=1.51, 95% CI=1.03–2.20), but not in East Asian populations (OR=1.19, 95% CI=0.80–1.77). Significant association between NAT2 acetylator phenotypes and esophageal cancer was found in population-based control subgroup (OR=1.63, 95% CI=1.07–2.50) but not in hospital-based control subgroup (OR=1.19, 95% CI=0.84–1.69). There is a significant association between NAT2 acetylator phenotype and esophageal cancer in both smokers (OR=1.681, 95% CI=1.179–2.395) and non-smokers (OR=1.614, 95% CI=1.173–2.222). In conclusion, NAT2 slow acetylator phenotype was a significant risk factor of ESCC in Asian populations.
Keywords: N-acetyltransferase 2, esophageal cancer, risk, meta analysis
