RGD Reference Report - Genetic identification of multiple loci that control breast cancer susceptibility in the rat - Rat Genome 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
RGD ID: 61081
Pubmed: PMID:9584103   (View Abstract at PubMed)
PMCID: PMC1460127   (View Article at PubMed Central)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
COP/OlaHsdRatbreast carcinoma MODEL: controlIAGP7,12-dimethyltetraphene RGD 
WF/NHsdRatbreast carcinoma MODEL: inducedIAGP7,12-dimethyltetraphene RGD 
Mcs2RatExperimental Mammary Neoplasms  IDA  RGD 
Mcs3RatExperimental Mammary Neoplasms  IDA  RGD 
Mcs4RatExperimental Mammary Neoplasms  IDA  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Mcs2Ratincreased mammary adenocarcinoma incidence  QTM  RGD 
Mcs3Ratincreased mammary adenocarcinoma incidence  QTM  RGD 
Mcs4Ratincreased mammary adenocarcinoma incidence  QTM  RGD 

Related Phenotype Data for this Reference

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Rat Strains:
Clinical Measurements:
Experimental Conditions:
Measurement Methods:
Objects Annotated

QTLs
Mcs2  (Mammary carcinoma susceptibility QTL 2)
Mcs3  (Mammary carcinoma susceptibility QTL 3)
Mcs4  (Mammary carcinoma susceptibility QTL 4)

Strains
COP  (NA)
COP/OlaHsd  (NA)
WF  (Wistar Furth)
WF/NHsd  (NA)

Objects referenced in this article
Marker D8Mgh13 D8Mgh13 Rattus norvegicus
Marker D1Mit11 D1Mit11 Rattus norvegicus
Marker D2Mit29 D2Mit29 Rattus norvegicus
Marker D1Mit2 D1Mit2 Rattus norvegicus
Marker D7Mit28 D7Mit28 Rattus norvegicus
Marker D7Mgh15 D7Mgh15 Rattus norvegicus
Marker D8Mgh6 D8Mgh6 Rattus norvegicus
Marker D2Rat3 D2Rat3 Rattus norvegicus
Marker D1Wox6 D1Wox6 Rattus norvegicus
Marker D2Uwm15 D2Uwm15 Rattus norvegicus
Marker D7Uwm9 D7Uwm9 Rattus norvegicus
Gene Cyp1a1 cytochrome P450, family 1, subfamily a, polypeptide 1 Rattus norvegicus
Gene Cyp1a2 cytochrome P450, family 1, subfamily a, polypeptide 2 Rattus norvegicus
QTL Mcs1 Mammary carcinoma susceptibility QTL 1 Rattus norvegicus

Additional Information