A meta-analysis of the association of N-acetyltransferase 2 gene (NAT2) variants with breast cancer

The N-acetyltransferase 2 gene (NAT2) product is an enzyme important in carcinogen metabolism via activation and detoxification pathways. Therefore, NAT2 variants may represent underlying susceptibility to breast cancer. Because a number of studies of the association of NAT2 with breast cancer have been published, the authors performed a meta-analysis. They extracted all relevant data to examine evidence for a main effect (i.e., the effect in a model that does not include any interactions) of NAT2 phenotype and genotype on breast cancer risk. They summarized the evidence for modification by smoking and meat intake, sources of exposure to aromatic and heterocyclic amines, respectively, which are metabolized by NAT2. The authors identified seven studies that measured NAT2 phenotype and 20 studies that deduced phenotype via genotyping. They found no evidence for heterogeneity (Cochran's Q statistic p=0.74) and no statistically significant increased risk from NAT2 acetylation (slow/rapid) for breast cancer (summary odds ratio=1.02, 95% confidence interval: 0.95, 1.08). These results suggest that there is no overall association between the NAT2 slow- or rapid-acetylation phenotype and breast cancer risk. However, some evidence suggests that smoking may modify this association.