The uncontrolled clonal expansion of a cell, which often leads to invasion of surrounding tissues and metastatic spread, produces cancer. A clear histologic and molecular genetic evolution from precancerous lesions to frankly malignant and invasive cancer has been defined for some tumors (e.g., colon and bladder cancers). In rare cases, mutations may occur and be passed on in the germline, resulting in genetic predisposition to cancer (i.e., familial cancer syndromes). Environmental factors are also thought to contribute to the development of cancer. Interactions between environmental factors and subtle germline genetic variations that distinguish individuals may in some cases constitute an important determinant of cancer risk within the general population. Finally, viral infection has been linked to the development of specific cancers. Oncogenes and proto-oncogenes, and germline genetic analysis and cancer risk assessment are covered. Also discussed are genetic alterations and abnormalities, tumor suppressor genes, tumor progression, genetic mechanisms of treatment sensitivity and resistance, and emerging trends in cancer genomics and risk assessment. Figures illustrate activation
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