NAT2 slow acetylation and bladder cancer risk: a metaanalysis of 22 case-control studies conducted in the general population

The NAT2 gene is involved in phase II detoxification of aromatic monoamines, a class of known bladder carcinogens. Certain allelic combinations result in the slow acetylation phenotype, which is thought to increase bladder cancer risk, We conducted a meta-analysis of all identifiable published case-control studies conducted in the general population that had examined the relationship of acetylation status and bladder cancer risk (22 studies, 2496 cases, 3340 controls). Using meta-analysis techniques that employed weighting based on individual-study variation, slow acetylators had an approximately 40% increase in risk compared with rapid acetylators [odds ratio (OR) 1.4, 95% confidence interval (CI) 1.2-1.6], Statistical tests indicated, however, that pooling of all studies, or of studies conducted in Caucasian populations, hid potentially important heterogeneity in the individual study results, and suggested that the relationship of NAT2 slow acetylation and bladder cancer risk might differ by geographical region. Studies conducted in Asia generated a summary OR of 2.1 (CI 1.2-3.8), in Europe, a summary OR of 1.4 (CI 1.2-1.6), and in the USA, a summary OR of 0.9 (CI 0.7-1.3). Among European studies, the relationship between NAT2 slow acetylation and bladder cancer risk did not differ by method used to assess acetylation status (older drug-based phenotyping methods: 10 studies, OR 1.5, CI 1.2-1.8; more recent NAT2 genotyping methods: four studies, OR 1.4, CI 1.1-1.7). Our results suggest that in most populations studied to date, NAT2 slow acetylation status is associated with a modest increase in bladder cancer risk. Pharmacogenetics 10:115-122 (C) 2000 Lippincott Williams & Wilkins.