The Cancer Genetic Markers of Susceptibility (CGEMS) project began in 2005 as a 3-year pilot study to identify inherited genetic susceptibility to prostate and breast cancer (cgems.cancer.gov). CGEMS has developed into a robust research program involving genome-wide association studies (GWASs) for dozens of different cancer phenotypes to identify common genetic variants that affect an individual’s risk of developing cancer. In collaboration with extramural scientists, NCI's Division of Cancer Epidemiology and Genetics (DCEG) has carried out genome-wide scans for common and/or highly lethal cancers extensively studied by the Division. CGEMS relies upon data from the NCI Consortium as well as collaborative case-control epidemiologic studies with biospecimens. By scanning the DNA collected from individuals participating in these cohort or case-control studies, scientists have identified common inherited genetic variants associated with cancer risk that may lead to new preventive, diagnostic, and therapeutic interventions. The pooling of large data sets provides the statistical power to quantify the risks associated with specific gene variants and exposures, and enables subset analyses that uncover gene-gene and gene-environment interactions. Researchers are applying fine-mapping and deep sequencing techniques to regions or loci identified by these scans to pinpoint the specific functional variants responsible for disease risk and the biologic mechanisms involved. Ultimately, findings from these studies may yield new preventive, diagnostic, and therapeutic interventions for cancer.