Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Adult
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Age Factors
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Arylamine N-Acetyltransferase / genetics*
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Base Pair Mismatch*
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Carrier Proteins
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Colorectal Neoplasms, Hereditary Nonpolyposis / epidemiology*
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Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
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DNA-Binding Proteins*
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Female
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Genetic Carrier Screening
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Genotype
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Humans
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Male
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Middle Aged
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MutL Protein Homolog 1
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MutS Homolog 2 Protein
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Neoplasm Proteins / genetics*
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Nuclear Proteins
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Phenotype
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Prevalence
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Proto-Oncogene Proteins / genetics*
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Switzerland / epidemiology
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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DNA-Binding Proteins
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MLH1 protein, human
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Neoplasm Proteins
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Nuclear Proteins
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Proto-Oncogene Proteins
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Arylamine N-Acetyltransferase
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NAT2 protein, human
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MSH2 protein, human
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MutL Protein Homolog 1
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MutS Homolog 2 Protein