A potent modifier of liver cancer risk on distal mouse chromosome 1: Linkage analysis and characterization of congenic lines

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 carcinoina development to distal chromosome 1, linked to the marker D1Mit33 with combined LODw scores of similar to5.9 (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-D1-Mit17 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.