Association Between NAT2 Polymorphism and Lung Cancer Risk: A Systematic Review and Meta-Analysis

Abstract

Lung cancer is the leading cause of cancer-related death worldwide and has a high incidence rate. N-Acetyltransferase 2 (NAT2) is a polymorphic xenobiotic enzyme, which can catalyze N-acetylation and O-acetylation of various carcinogens such as aromatic, heterocyclic amines and hydrazines. At present, many studies have explored the effects of NAT2 polymorphism on lung cancer, but we found inconsistent results. We researched 18 published studies, involving 4,016 patients and 5,469 controls, to more accurately assess the effects of NAT2 polymorphism on lung cancer risk and to investigate whether smoking is associated. We used STATA software to analyze the extracted data and used STATA for subgroup analysis, sensitivity analysis, and to perform publication bias tests. To determine the correlation, we used the crude odds ratio (ORs) with 95% confidence interval (CIs). Our study was prospectively registered in PROSPERO (CRD42020159737). The odds ratio was 1.53 (95% CI: 1.21-1.95, I² = 45.2%, P=0.104) for the NAT2 slow + intermediate phenotype versus rapid phenotype. The results suggested that people with NAT2 non-rapid (slow + intermediate) phenotype have a significantly increased risk of lung cancer. In addition, NAT2 rapid phenotype was significantly associated with reduced risk of lung cancer, compared with slow phenotype or intermediate phenotype (slow phenotype vs . rapid phenotype: OR: 1.61, 95% CI: 1.07-2.42, I²= 50%, P= 0.075; intermediate phenotype vs . rapid phenotype: OR: 1.47, 95% CI: 1.15-1.88, I²= 40.3%, P= 0.137).

Keywords: NAT2; genetic polymorphism; lung cancer; phenotype; systematic review.

Figure 1

The study selection process of this meta-analysis.

Figure 2

The meta-analysis results. (A) Meta-analysis for the association between NAT2 polymorphism and lung cancer risk (slow + intermediate versus rapid). OR is represented as a square and its 95% CI estimate is represented as two horizontal lines. The weight has reflected the area of the square (inverse variance). The diamond represents the combined results of all the studies. (B) Meta-analysis for the association between NAT2 polymorphism and lung cancer risk (slow versus intermediate + rapid).

Figure 3

Results of comparison of three NAT2 acetylator statuses. (A) Meta-analysis for the association between NAT2 polymorphism and lung cancer risk (slow versus rapid). (B) Meta-analysis for the association between NAT2 polymorphism and lung cancer risk (intermediate versus rapid). (C) Meta-analysis for the association between NAT2 polymorphism and lung cancer risk (slow versus intermediate).

Figure 4

Results of the sensitivity analysis. The middle vertical line represents the combined OR value of 18 studies, and the left and right vertical lines represent the 95% CI. Each dashed line perpendicular to the vertical line represents the results of combined studies after excluding corresponding studies; the circle represents the OR value of combined studies, and the left and right boundaries represent the 95% CI.

Figure 5

Begg’s funnel plots and Egger’s tests for publication bias in the selection of studies. (A) Begg’s Test of the primary model. (B) Egger’s test of the primary model. (C) Begg’s Test of the recessive model. (D) Egger’s test of the recessive model.