Novel approaches to identify low-penetrance cancer susceptibility genes using mouse models.
Studies of cancer predisposition have largely concentrated on the role of high-penetrance susceptibility genes. Less than 10% of the total human tumor burden, however, is accounted for by mutations in these genes. More genetic variation in cancer risk is likely to be due to commoner but lower penetrance alleles. In man, such modifier genes will be difficult to find since they do not segregate as single Mendelian traits. The mouse offers a powerful system for studying polygenic traits such as cancer and has been widely used for this purpose. Novel approaches that might accelerate the identification of these low-penetrance cancer susceptibility genes by using mouse models will be discussed.
de Koning
John P
JP
UCSF Comprehensive Cancer Center and Cancer Research Institute, Department of Biochemistry and Biophysics, University of California San Francisco, 2340 Sutter Street, San Francisco, CA 94115, USA.
Mao
Jian-Hua
JH
Balmain
Allan
A
D000483:Alleles; D000818:Animals; D004195:Disease Models, Animal; D016147:Genes, Tumor Suppressor; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D020412:Multifactorial Inheritance; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D019683:Penetrance; D010641:Phenotype; D040641:Quantitative Trait Loci