Predicting who may carry inherited susceptibility to cancer
Cancer is caused by changes (mutations) in our genes. While many of these changes occur during one's lifetime, some are inherited (germline mutations). Genetic research has identified a number of genes, inherited mutations of which confer a significantly increased risk of one of more types of cancer. Important examples of these gens are the BRCA1 and BRCA2 genes, responsible for the familial breast/ovarian cancer syndrome, certain mismathch repair genes responsible for familial colorectal cacner, the APC gene, reponsible for familial polyposis, and genes for melanoma, pancreas and others.
Most mutations of cancer genes do not determine the fate of an individual. Genetic effects are therefore characterized probabilistically by penetrance functions, that is probability distributions of developing cancer by age, given a specific genetic variant, and prevalence functions, that is frequencies of mutation by population strata. Identifying individuals at high risk of cancer because of inherited genetic susceptibility is complex and increasingly important. Probabilistic prediction algorithms that exploit domain knowledge of Mendelian inheritance and other biological characteristics of susceptibility genes have successfully contributed to improved screening, prevention, and genetic testing, and to the design and analysis of cancer studies.