NAT1 genotypic and phenotypic contribution to urinary bladder cancer risk: a systematic review and meta-analysis

N-acetyltransferase 1 (NAT1), a polymorphic Phase II enzyme, plays an essential role in metabolizing heterocyclic and aromatic amines, which are implicated in urinary bladder cancer (BCa). This systematic review investigates a possible association between the different NAT1 genetic polymorphisms and BCa risk. Medline, PubMed, EMBASE, Scopus, Web of Science, OpenGrey, and BASE databases were searched to identify eligible studies. The random-effect model was used to calculate pooled effects estimates. Statistical heterogeneity was tested with Chi-square and I². Twenty case-control studies, including 5606 cases and 6620 controls, met the inclusion criteria. Pooled odds ratios (OR) analyses showed a statistically significant difference in NAT1*10 versus non-NAT1*10 acetylators in the total sample (OR: 0.87; 95% CI: 0.79-0.96) but was borderline among Caucasians (OR: 0.88 with 95% CI: 0.77-1.01). No statistically significant differences in BCa risk were found for: NAT1*10 versus NAT1*4 wild type (OR: 0.97; 95% CI: 0.78-1.19), NAT1 'Fast' versus 'Normal' acetylators (OR: 1.03; 95% CI: 0.84-1.27), and NAT1 'Slow' versus 'Fast' (OR: 2.32; 95% CI: 0.93-5.84) or 'Slow' versus 'Normal' acetylators (OR: 1.84; 95% CI: 0.92-3.68). When stratifying by smoking status, no statistically significant differences in BCa risk were found for NAT1*10 versus non-NAT1*10 acetylators among the different subgroups. Our study suggests a modest protective role for NAT1*10 and a possible risk contributory role for slow acetylation genotypes in BCa risk. Further research is recommended to confirm these associations.