Genetic determination of susceptibility to estrogen-induced mammary cancer in the ACI rat: mapping of Emca1 and Emca2 to chromosomes 5 and 18.
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.
Gould
Karen A
KA
Eppley Institute for Research in Cancer, Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska 68198-5805, USA.
Tochacek
Martin
M
Schaffer
Beverly S
BS
Reindl
Tanya M
TM
Murrin
Clare R
CR
Lachel
Cynthia M
CM
VanderWoude
Eric A
EA
Pennington
Karen L
KL
Flood
Lisa A
LA
Bynote
Kimberly K
KK
Meza
Jane L
JL
Newton
Michael A
MA
Shull
James D
JD
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
D005819:Genetic Markers; D004958:Estradiol