Genetics of lung cancer: implications for early detection and prevention

Human lung cancer is a complex disease originating in different cell types. In general, tumorigenesis in the lung appears to involve a complex series of molecular, genetic, and histopathologic events, leading to the transformation of normal cells to malignant cells. It is generally believed that it is the accumulation of biologic changes, not necessarily the order in which they occur, that could best describe the transformation of cells. Our knowledge of genetic changes during tumorigenesis in the lung is limited and comes from studies involving animal models and frankly malignant lung tissues. Such studies can be questioned as to their applicability in primary prevention. A vast majority of genetic changes occurring during the preclinical stage are yet to be documented. Study of these preclinical changes would offer a better opportunity for early detection and prevention. Oncogenes and tumor suppressor genes have potential for use as biomarkers in identifying high-risk groups and in early detection. The interaction between nature and nurture is nowhere as evident as in cancers of the lung, which are influenced by environmental exposure, familial inheritance, and metabolic phenotypes. The gene-environment interaction provides several targets for prevention and early detection. Biomarkers, if validated for specificity, sensitivity, and predictive values, could act as markers of exposure, susceptibility, progression, and disease. Validation of these markers, however, would require well-characterized, prospectively collected samples, representing normal, premalignant, malignant, invasive, and metastatic conditions. The NCI has started an initiative for a tissue bank of prostate, bladder, colorectum, head and neck, and lung cancers. Clinical and epidemiological information are also collected for each sample. Study of genetic and molecular changes in collected samples should shed light on the involvement of these changes in the transformation of normal to malignant tissues.