RGD Reference Report - Genetic bases of estrogen-induced tumorigenesis in the rat: mapping of loci controlling susceptibility to mammary cancer in a Brown Norway x ACI intercross. - Rat Genome Database

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Genetic bases of estrogen-induced tumorigenesis in the rat: mapping of loci controlling susceptibility to mammary cancer in a Brown Norway x ACI intercross.

Authors: Schaffer, BS  Lachel, CM  Pennington, KL  Murrin, CR  Strecker, TE  Tochacek, M  Gould, KA  Meza, JL  McComb, RD  Shull, JD 
Citation: Schaffer BS, etal., Cancer Res. 2006 Aug 1;66(15):7793-800.
RGD ID: 1642522
Pubmed: PMID:16885383   (View Abstract at PubMed)
DOI: DOI:10.1158/0008-5472.CAN-06-0143   (Journal Full-text)

Exposure to estrogens is associated with an increased risk of breast cancer. Our laboratory has shown that the ACI rat is uniquely susceptible to 17beta-estradiol (E2)-induced mammary cancer. We previously mapped two loci, Emca1 and Emca2 (estrogen-induced mammary cancer), that act independently to determine susceptibility to E2-induced mammary cancer in crosses between the susceptible ACI rat strain and the genetically related, but resistant, Copenhagen (COP) rat strain. In this study, we evaluate susceptibility to E2-induced mammary cancer in a cross between the ACI strain and the unrelated Brown Norway (BN) rat strain. Whereas nearly 100% of the ACI rats developed mammary cancer when treated continuously with E2, BN rats did not develop palpable mammary cancer during the 196-day course of E2 treatment. Susceptibility to E2-induced mammary cancer segregated as a dominant or incompletely dominant trait in a cross between BN females and ACI males. In a population of 251 female (BN x ACI)F(2) rats, we observed evidence for a total of five genetic determinants of susceptibility. Two loci, Emca4 and Emca5, were identified when mammary cancer status at sacrifice was evaluated as the phenotype, and three additional loci, Emca6, Emca7, and Emca8, were identified when mammary cancer number was evaluated as the phenotype. A total of three genetic interactions were identified. These data indicate that susceptibility to E2-induced mammary cancer in the BN x ACI cross behaves as a complex trait controlled by at least five loci and multiple gene-gene interactions.



Disease Annotations    

Phenotype Annotations    

Mammalian Phenotype

Objects Annotated

QTLs
Emca4  (Estrogen-induced mammary cancer QTL 4)
Emca5  (Estrogen-induced mammary cancer QTL 5)
Emca6  (Estrogen-induced mammary cancer QTL 6)
Emca7  (Estrogen-induced mammary cancer QTL 7)
Emca8  (Estrogen-induced mammary cancer QTL 8)

Strains
ACI/SegHsd  (NA)
BN/SsNHsd  (NA)

Objects referenced in this article
QTL Emca1 Estrogen-induced mammary cancer QTL 1 Rattus norvegicus
QTL Emca2 Estrogen-induced mammary cancer QTL 2 Rattus norvegicus
QTL Ept5 Estrogen-induced pituitary tumorigenesis QTL 5 Rattus norvegicus
QTL Ept7 Estrogen-induced pituitary tumorigenesis QTL 7 Rattus norvegicus

Additional Information