Genetic determination of susceptibility to estrogen-induced mammary cancer in the ACI rat

Mapping of Emca1 and Emca2 to chromosomes 5 and 18

Karen A Gould, Martin Tochacek, Beverly S. Schaffer, Tanya M. Reindl, Clare R. Murrin, Cynthia M. Lachel, Eric A. VanderWoude, Karen L. Pennington, Lisa A. Flood, Kimberly K. Bynote, Jane L Meza, Michael A. Newton, James D. Shull

Research output: Contribution to journalArticle

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Abstract

Hormonal, genetic, and environmental factors play major roles in the complex etiology of breast cancer. When treated continuously with 17β-estradiol (E2), the ACI rat exhibits a genetically conferred propensity to develop mammary cancer. The susceptibility of the ACI rat to E2-induced mammary cancer appears to segregate as an incompletely dominant trait in crosses to the resistant Copenhagen (COP) strain. In both (ACI × COP)F 2 and (COP × ACI)F2 populations, we find strong evidence for a major genetic determinant of susceptibility to E2-induced mammary cancer on distal rat chromosome 5. Our data are most consistent with a model in which the ACI allele of this locus, termed Emca1 (estrogen-induced mammary cancer 1), acts in an incompletely dominant manner to increase both tumor incidence and tumor multiplicity as well as to reduce tumor latency in these populations. We also find evidence suggestive of a second locus, Emca2, on chromosome 18 in the (ACI × COP)F2 population. The ACI allele of Emca2 acts in a dominant manner to increase incidence and decrease latency. Together, Emca1 and Emca2 act independently to modify susceptibility to E2-induced mammary cancer.

Original languageEnglish (US)
Pages (from-to)2113-2125
Number of pages13
JournalGenetics
Volume168
Issue number4
DOIs
StatePublished - Dec 1 2004

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Inbred ACI Rats
Chromosomes, Human, Pair 18
Chromosomes, Human, Pair 5
Genetic Predisposition to Disease
Estrogens
Breast Neoplasms
Alleles
Population
Neoplasms
Incidence
Estradiol

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Genetic determination of susceptibility to estrogen-induced mammary cancer in the ACI rat : Mapping of Emca1 and Emca2 to chromosomes 5 and 18. / Gould, Karen A; Tochacek, Martin; Schaffer, Beverly S.; Reindl, Tanya M.; Murrin, Clare R.; Lachel, Cynthia M.; VanderWoude, Eric A.; Pennington, Karen L.; Flood, Lisa A.; Bynote, Kimberly K.; Meza, Jane L; Newton, Michael A.; Shull, James D.

In: Genetics, Vol. 168, No. 4, 01.12.2004, p. 2113-2125.

Research output: Contribution to journalArticle

Gould, KA, Tochacek, M, Schaffer, BS, Reindl, TM, Murrin, CR, Lachel, CM, VanderWoude, EA, Pennington, KL, Flood, LA, Bynote, KK, Meza, JL, Newton, MA & Shull, JD 2004, 'Genetic determination of susceptibility to estrogen-induced mammary cancer in the ACI rat: Mapping of Emca1 and Emca2 to chromosomes 5 and 18', Genetics, vol. 168, no. 4, pp. 2113-2125. https://doi.org/10.1534/genetics.104.033878
Gould, Karen A ; Tochacek, Martin ; Schaffer, Beverly S. ; Reindl, Tanya M. ; Murrin, Clare R. ; Lachel, Cynthia M. ; VanderWoude, Eric A. ; Pennington, Karen L. ; Flood, Lisa A. ; Bynote, Kimberly K. ; Meza, Jane L ; Newton, Michael A. ; Shull, James D. / Genetic determination of susceptibility to estrogen-induced mammary cancer in the ACI rat : Mapping of Emca1 and Emca2 to chromosomes 5 and 18. In: Genetics. 2004 ; Vol. 168, No. 4. pp. 2113-2125.
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