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Genetics, Vol. 167, 859-866, June 2004, Copyright © 2004
doi:10.1534/genetics.103.024521
A Potent Modifier of Liver Cancer Risk on Distal Mouse Chromosome 1
Linkage Analysis and Characterization of Congenic Lines
Andrea Bilger, L. Michelle Bennett1, Reynaldo A. Carabeo2, Teresa A. Chiaverotti3, Cecily Dvorak4, Kristin M. Liss, Susan A. Schadewald, Henry C. Pitot and Norman R. Drinkwater5
McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, Wisconsin 53706
5 Corresponding author: McArdle Laboratory for Cancer Research, 1400 University Ave., University of Wisconsin Medical School, Madison, WI 53706.
E-mail: drinkwater{at}oncology.wisc.edu
The C3H/HeJ (C3H) and CBA/J (CBA) mouse strains are classical mouse models of cancer susceptibility, exhibiting high risks for both spontaneous and chemically induced liver cancer. By analysis of backcrosses and intercrosses between C3H or CBA and resistant B6 mice, we have mapped a potent modifier of hepatocellular carcinoma development to distal chromosome 1, linked to the marker D1Mit33 with combined LODW scores of 
5.9 (C3H) and 6.5 (CBA). We previously identified this region as one of two that modify susceptibility in the more distantly related C57BR/cdJ (BR) strain. Congenic B6.C3H(D1Mit5-D1Mit17) and B6.BR(D1Mit5-D1Mit17) mice developed significantly more liver tumors than B6 mice did (6- to 13-fold, P < 10–11, in males; 3- to 4-fold, P < 10–3, in females). Thus, distal chromosome 1 carries one or more genes that are sufficient to confer susceptibility to liver cancer.
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