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.