Isolation of two regions on rat chromosomes 5 and 18 affecting mammary cancer susceptibility

We previously mapped several quantitative trait loci (QTLs) con-trolling DMBA-induced mammary tumor development in female rats derived from a SPRD-Cu3 (susceptible strain) 3WKY (resist-ant strain) cross. Two of these QTLs were assigned to chromosomes 5 and 18. In the present study, we generated and characterized con-genic strains in which a segment of WKY chromosomes 5 or 18 was introduced in the SPRD-Cu3 genetic background, thereby physi-cally demonstrating that each of these two chromosomes controls mammary tumor multiplicity. The chromosome 5 QTL (Mcstm1) accounts for 7 tumors per animal (versus a total of 11 tumors per SPRD-Cu3 rat). The chromosome 18 QTL (Mcstm2) accounts for 3 tumors per animal and is the first chemically-induced mammary cancer susceptibility locus assigned to this chromosome. In addi-tion, the Mcstm1 region was shown to also controls tumor latency. These loci thus play a major role in chemically-induced mammar