RGD Reference Report - Genetic identification of multiple loci that control breast cancer susceptibility in the rat - Chinchilla Research Resource Database
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Genetic identification of multiple loci that control breast cancer susceptibility in the rat

Authors: Shepel, LA  Lan, H  Haag, JD  Brasic, GM  Gheen, ME  Simon, JS  Hoff, P  Newton, MA  Gould, MN 
Citation: Shepel LA, etal., Genetics 1998 May;149(1):289-99
CRRD ID: 61081
Pubmed: (View Article at PubMed) PMID:9584103

We have used a rat model of induced mammary carcinomas in an effort to identify breast cancer susceptibility genes. Using genetic crosses between the carcinoma-resistant Copenhagen (COP) and carcinoma-sensitive Wistar-Furth rats, we have confirmed the identification of the Mcs1 locus that modulates tumor number. We have now also identified two additional loci, Mcs2 and Mcs3. These three loci map to chromosomes 2, 7, and 1, respectively, and interact additively to suppress mammary carcinoma development in the COP strain. They are responsible for a major portion of the tumor-resistant phenotype of the COP rat. No loss of heterozygosity was observed surrounding the three loci. A fourth COP locus, Mcs4, has also been identified on chromosome 8 and acts in contrast to increase the number of carcinomas. These results show that mammary carcinoma susceptibility in the COP rat is a polygenic trait. Interestingly, a polymorphism in the human genomic region homologous to the rat Mcs4 region is associated with an increased breast cancer risk in African-American women. The isolation of the Mcs genes may help elucidate novel mechanisms of carcinogenesis, provide information important for human breast cancer risk estimation, and also provide unique drug discovery targets for breast cancer prevention.

Annotation

Disease Annotations    

Phenotype Annotations    

Mammalian Phenotype
Experimental Data Annotations    

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Objects Annotated

Objects referenced in this article
0 D8Mgh13 D8Mgh13 All species
0 D1Mit11 D1Mit11 All species
0 D2Mit29 D2Mit29 All species
0 D1Mit2 D1Mit2 All species
0 D7Mit28 D7Mit28 All species
0 D7Mgh15 D7Mgh15 All species
0 D8Mgh6 D8Mgh6 All species
0 D2Rat3 D2Rat3 All species
0 D1Wox6 D1Wox6 All species
0 D2Uwm15 D2Uwm15 All species
0 D7Uwm9 D7Uwm9 All species
0 COP null All species
0 Cyp1a1 cytochrome P450, family 1, subfamily a, polypeptide 1 All species
0 Cyp1a2 cytochrome P450, family 1, subfamily a, polypeptide 2 All species
0 Mcs1 Mammary carcinoma susceptibility QTL 1 All species
0 WF Wistar Furth All species

Additional Information