N-acetyltransferase 2 influences cancer prevalence in hMLH1/hMSH2 mutation carriers.
Hereditary nonpolyposis colorectal cancer (HNPCC), an inherited cancer predisposition syndrome, has been associated with germline mutations in DNA mismatch repair (MMR) genes. Because a deficiency in MMR does not predict a specific cancer phenotype, modifying genes may account in part for the variation in disease expression. We determined the N-acetyltransferase 2 (NAT2) genotype in 26 unaffected and 52 cancer-affected hMLH1/hMSH2 mutation carriers coming from 21 Swiss HNPCC families. Slow acetylators were found to be significantly (P < 0.03) more prevalent in the group of affected mutation carriers. Our results suggest a protective effect of the NAT2 rapid acetylator phenotype, an observation that could have implications for genetic counseling and management of MMR gene mutation carriers.
Research Group Human Genetics, University Hospital, Basel, Switzerland.
K
K
Heinimann
R J
RJ
Scott
P
P
Chappuis
W
W
Weber
H
H
Müller
Z
Z
Dobbie
P
P
Hutter
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000367:Age Factors; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D020137:Base Pair Mismatch; D002352:Carrier Proteins; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000453:epidemiology* / Q000235:genetics*; D004268:DNA-Binding Proteins; D005260:Female; D006580:Genetic Carrier Screening; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D010641:Phenotype; D015995:Prevalence; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013557:Switzerland / Q000453:epidemiology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein