N-acetyltransferase 2 influences cancer prevalence in hMLH1/hMSH2 mutationcarriers

Hereditary nonpolyposis colorectal cancer (HNPCC), an inherited cancer pred isposition syndrome, has been associated with germline mutations in DNA mis match repair (MMR) genes. Because a deficiency in MMR does not predict a sp ecific cancer phenotype, modifying gents may account in part for the variat ion in disease expression, We determined the N-acetyltransferase 2 (NAT2) g enotype in 26 unaffected and 52 cancer-affected hMLH1/hMSH2 mutation carrie rs coming from 21 Swiss HNPCC families. Slow acetylators were found to be s ignificantly (P < 0.03) more prevalent in the group of affected mutation ca rriers. Our results suggest a protective effect of the NAT2 rapid acetylato r phenotype, an observation that could have implications for genetic counse ling and management of hMMR gene mutation carriers.