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Carcinogenesis Advance Access published online on July 4, 2003
Carcinogenesis, doi:10.1093/carcin/bgg112
© 2003 by Oxford University Press
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© 2003 Oxford University Press

CANCER BIOLOGY

Physical evidence of Mcs5, a QTL controlling mammary carcinoma susceptibility, in congenic rats

David J. Samuelson 1, Jill D. Haag 1, Hong Lan 1, Dinelli M. Monson 1, Millicent A. Shultz 1, Bradley D. Kolman 1, and Michael N. Gould 1

1 McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, 1400 University Avenue, Madison, WI 53706-1599, USA

Received 17 March 2003 ; revised 19 May 2003 ; accepted 21 June 2003

Abstract

Genetic susceptibility to breast cancer is influenced by high- and low-penetrance genes. The low-penetrance genes contributing to increased and decreased risk likely exist at appreciable frequencies in the human population. To identify high-frequency, low-penetrance modifier genes, we are using a rat genetic model. Eight quantitative trait loci, named mammary carcinoma susceptibility (Mcs) loci, have been genetically identified in two rat strains, Wistar-Kyoto (WKy) and Copenhagen. These strains are resistant to developing mammary cancer compared to susceptible Wistar-Furth (WF) female rats. Here we provide physical evidence of the existence of Mcs5 in the resistant WKy rat and further narrow the candidate region defining the QTL. Two congenic rat lines (C and D) containing large segments of the WKy Mcs5 QTL on chromosome 5 were generated on a WF background. The minimal WKy interval from markers D5Wox7 and D5Uwm37 (line C) conferred resistance to developing 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinomas. Line C females that were homozygous for the WKy allele at this interval averaged 1.1±0.3 carcinomas/rat compared to 6.9±0.4 average carcinomas/rat for WF control females (p<0.01). Line D females containing the minimal WKy interval from D5Rat26 to D5Uwm42, were as susceptible to developing mammary carcinomas as WF controls (5.7±0.6 vs. 6.9±0.4, respectively). The WKy region in common to these lines from D5Rat26 to D5Uwm37 is thus not expected to contain Mcs5-associated genes. Based on results presented here, the Mcs5 locus has been physically located within a congenic interval on rat chromosome 5 between markers D5Uwm8 and D5Rat26.


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