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.
Heinimann
K
K
Research Group Human Genetics, University Hospital, Basel, Switzerland.
Scott
R J
RJ
Chappuis
P
P
Weber
W
W
Müller
H
H
Dobbie
Z
Z
Hutter
P
P
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