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MUTYH and the mismatch repair system: partners in crime?
- Source :
-
Human Genetics . Mar2006, Vol. 119 Issue 1/2, p206-211. 6p. 3 Charts. - Publication Year :
- 2006
-
Abstract
- Biallelic germline mutations of MUTYH—a gene encoding a base excision repair protein—are associated with an increased susceptibility of colorectal cancer. Whether monoallelic MUTYH mutations also increase cancer risk is not yet clear, although there is some evidence suggesting a slight increase of risk. As the MUTYH protein interacts with the mismatch repair (MMR) system, we hypothesised that the combination of a monoallelic MUTYH mutation with an MMR gene mutation increases cancer risk. We therefore investigated the prevalence of monoallelic MUTYH mutations in carriers of a germline MMR mutation: 40 carriers of a truncating mutation (group I) and 36 of a missense mutation (group II). These patients had been diagnosed with either colorectal or endometrial cancer. We compared their MUTYH mutation frequencies with those observed in a group of 134 Dutch colorectal and endometrial cancer patients without an MMR gene mutation (0.7%) and those reported for Caucasian controls (1.5%). In group I one monoallelic MUTYH mutation was found (2.5%). In group II five monoallelic germline MUTYH mutations were found (14%), four of them in MSH6 missense mutation carriers (20%). Of all patients with an MMR gene mutation, only those with a missense mutation showed a significantly higher frequency of (monoallelic) MUTYH mutations than the Dutch cancer patients without MMR gene mutations ( P=0.002) and the published controls ( P=0.001). These results warrant further study to test the hypothesis of mutations in MMR genes (in particular MSH6) and MUTYH acting together to increase cancer risk. [ABSTRACT FROM AUTHOR]
- Subjects :
- *GENETIC mutation
*CARRIER proteins
*COLON cancer
*CANCER
*GENETICS
*MEDICAL genetics
Subjects
Details
- Language :
- English
- ISSN :
- 03406717
- Volume :
- 119
- Issue :
- 1/2
- Database :
- Academic Search Index
- Journal :
- Human Genetics
- Publication Type :
- Academic Journal
- Accession number :
- 20423938
- Full Text :
- https://doi.org/10.1007/s00439-005-0118-5