Epidemiological approaches to the identification of cancer predisposition genes

The goal of appropriate epidemiologic approaches to identify cancer susceptibility genes is to maximize the potential of identifying causal relationships and minimize the potential that spurious relationships will be found. It is similarly important to target the appropriate approach for the identification of specific types of genes. Germline mutations in high-penetrance genes often confer Mendelian patterns of inheritance, and can be optimally identified by segregation and genetic linkage analysis methods. In contrast, low-penetrance genes may not confer Mendelian patterns of inheritance, and may be involved in cancer etiology only through complex interactions with other genes and exposures. Association studies may be more appropriate means of determining a role for these genes in cancer etiology.