title: Genetic determination of susceptibility to estrogen-induced mammary cancer in the ACI rat: mapping of Emca1 and Emca2 to chromosomes 5 and 18.
abstract: Hormonal, genetic, and environmental factors play major roles in the complex etiology of breast cancer. When treated continuously with 17beta-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 x COP)F(2) and (COP x ACI)F(2) 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 x COP)F(2) 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.
authors.affiliation: Eppley Institute for Research in Cancer, Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska 68198-5805, USA.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Gould
authors.forename: Martin
authors.initials: M
authors.lastname: Tochacek
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Schaffer
authors.forename: Tanya M
authors.initials: TM
authors.lastname: Reindl
authors.forename: Clare R
authors.initials: CR
authors.lastname: Murrin
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Lachel
authors.forename: Eric A
authors.initials: EA
authors.lastname: VanderWoude
authors.forename: Karen L
authors.initials: KL
authors.lastname: Pennington
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Flood
authors.forename: Kimberly K
authors.initials: KK
authors.lastname: Bynote
authors.forename: Jane L
authors.initials: JL
authors.lastname: Meza
authors.forename: Michael A
authors.initials: MA
authors.lastname: Newton
authors.forename: James D
authors.initials: JD
authors.lastname: Shull
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics*; D051381:Rats; D011912:Rats, Inbred ACI
chemical_list: D005819:Genetic Markers; D004958:Estradiol