Association of N-acetyltransferases 1 and 2 Polymorphisms with Susceptibility to Head and Neck Cancers-A Meta-Analysis, Meta-Regression, and Trial Sequential Analysis

Background and objective: N-acetyltransferases 1 and 2 (NAT1 and NAT2) genes have polymorphisms in accordance with slow and rapid acetylator phenotypes with a role in the development of head and neck cancers (HNCs). Herein, we aimed to evaluate the association of NAT1 and NAT2 polymorphisms with susceptibility to HNCs in an updated meta-analysis. Materials and methods: A search was comprehensively performed in four databases (Web of Science, Scopus, PubMed/Medline, and Cochrane Library until 8 July 2021). The effect sizes, odds ratio (OR) along with 95% confidence interval (CI) were computed. Trial sequential analysis (TSA), publication bias and sensitivity analysis were conducted. Results: Twenty-eight articles including eight studies reporting NAT1 polymorphism and twenty-five studies reporting NAT2 polymorphism were involved in the meta-analysis. The results showed that individuals with slow acetylators of NAT2 polymorphism are at higher risk for HNC OR: 1.22 (95% CI: 1.02, 1.46; p = 0.03). On subgroup analysis, ethnicity, control source, and genotyping methods were found to be significant factors in the association of NAT2 polymorphism with the HNC risk. TSA identified that the amount of information was not large enough and that more studies are needed to establish associations. Conclusions: Slow acetylators in NAT2 polymorphism were related to a high risk of HNC. However, there was no relationship between NAT1 polymorphism and the risk of HNC.