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- Title
MUTYH and the mismatch repair system: partners in crime?
- Authors
Niessen, Renée; Sijmons, Rolf H.; Ou, J.; Olthof, Sandra G. M.; Osinga, Jan; Ligtenberg, Marjolijn J.; Hogervorst, Frans B. L.; Weiss, Marjan M.; Tops, Carli M. J.; Hes, Frederik J.; de Bock, Geertruida H.; Buys, Charles H. C.; Kleibeuker, Jan H.; Hofstra, Robert M. W.
- 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.
- Subjects
GENETIC mutation; CARRIER proteins; COLON cancer; CANCER; GENETICS; MEDICAL genetics
- Publication
Human Genetics, 2006, Vol 119, Issue 1/2, p206
- ISSN
0340-6717
- Publication type
Article
- DOI
10.1007/s00439-005-0118-5