Some families are heavily affected by cancer and twin studies suggest that 1/3 of cancer risk can be attributed to genetic factors . The hereditary cancer syndromes caused by >100 highly-penetrant genes  account for less than 5% of cancer . Thus we are unable to identify causative mutations in many families with strong histories of cancer. The goal of this database is to collect samples from individuals in high-risk families to identify genetic variation responsible for cancer risk. This germ line genetic variation may be encoded in single nucleotide and structural variations, and our studies will seek both types of variation, when appropriate. When a cancer-associated mutation is identified in a family, I can perform genetic testing and propose intensive surveillance, cancer-preventing medications and risk reducing surgery. In the absence of a known syndrome, I have few risk assessment tools or medical interventions. This study will help to develop and validate genetic risk assessment tools. It may also be used to identify genetic variations that influence a patient’s response to cancer preventing or treating medications. While the findings of this study will not influence the care of enrolled patients, it will form the basis for influencing clinical practice in the next decades.