Infrequent but important, the Li-Fraumeni syndrome is a familial tendency to common tumors such as breast cancer, sarcomas, and central nervous system tumors. In cancers that occur in the Li-Fraumeni syndrome, the tumor suppressor gene p53 has been found to be inactivated by a point mutation. Healthy carriers of p53 mutations can be placed under medical surveillance. Molecular epidemiological studies may identify individuals at high risk. Lung cancer provides another example of the interaction between genetic and environmental factors in the development of neoplasia.
Smoking is the major cause of lung cancer.
However, although lung cancer develops in 10 percent of individuals with a history of 40 pack-years of smoking, it does not occur in 90 percent of such smokers, which suggests that genetic and other factors contribute to the risk of lung cancer. Most chemical carcinogens, including those present in cigarette smoke, must be activated enzymatically by the cytochrome P 450 system for carcinogenesis to occur. The cytochrome P 450 system includes enzymes that activate and inactivate chemical carcinogens. An imbalance of these enzymes that favors carcinogen activation is associated with an increased risk of lung cancer. The interplay of environmental and genetic factors in lung cancer has been clearly defined.