TY - JOUR
T1 - Genetic determination of susceptibility to estrogen-induced mammary cancer in the ACI rat
T2 - Mapping of Emca1 and Emca2 to chromosomes 5 and 18
AU - Gould, Karen A.
AU - Tochacek, Martin
AU - Schaffer, Beverly S.
AU - Reindl, Tanya M.
AU - Murrin, Clare R.
AU - Lachel, Cynthia M.
AU - VanderWoude, Eric A.
AU - Pennington, Karen L.
AU - Flood, Lisa A.
AU - Bynote, Kimberly K.
AU - Meza, Jane L.
AU - Newton, Michael A.
AU - Shull, James D.
PY - 2004/12
Y1 - 2004/12
N2 - 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.
AB - 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.
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U2 - 10.1534/genetics.104.033878
DO - 10.1534/genetics.104.033878
M3 - Article
C2 - 15611180
AN - SCOPUS:19944428906
SN - 0016-6731
VL - 168
SP - 2113
EP - 2125
JO - Genetics
JF - Genetics
IS - 4
ER -