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Polymorphisms in N-acetyltransferase (NAT) enzymes) are thought to affect the metabolism of carcinogenic chemicals in tobacco smoke, and thus an individual's risk of smoking-associated cancer. Comparing 230 bladder cancer patients with 203 matched controls, Taylor et al. found that the high-activity *10 allele of the NAT1 gene increased bladder cancer risk in smokers [Taylor, J.A. et al. (1998) Cancer Research 58, 3603-3610 (Abstract)]. Genotype for the NAT2 enzyme had no effect on bladder cancer risk, unless it was combined both with smoking and with the NAT1*10 allele.

Comment: This paper illustrates the complex nature of the task of teasing out the genetic and environmental influences on disease risk, and the pitfalls of trying to predict risk on the basis of single-gene variants. And a further cautionary note against simple conclusions: in another recent paper, Bouchardy et al. report that the NAT1*10 allele decreased the risk of lung cancer among French Canadian smokers, i.e. the opposite effect from that found by Taylor et al. for bladder cancer [Bouchardy, C et al. (1998) Pharmacogenetics 8, 291-298 (Abstract)].