Familial and Sporadic Neoplasia

Most human cancers are "sporadic" because there is no identifiable inherited gene involved, but the cancers developed as a result of environmental factors (carcinogens such as cigarette smoke) that randomly induced mutations in cells that led to uncontrolled growth. Such factors are encountered throughout life and act over a long period of time; hence, most sporadic cancers occur in adults. Most affected persons have one primary site, and that site is where you would expect most cancers to be (breast, lung, prostate, colon, etc.)

Familial cancers have a specific gene with a defined inheritance pattern. Thus, one is born with "one strike" and it is a matter of years before another event triggers the cancer growth. They tend to occur at a younger age than sporadic cancers. One form of classic familial cancer syndrome involves a tumor suppressor gene, with the "two hit" hypothesis. A person inherits a bad p53 gene, for example, (first hit), but still has another functional copy of this gene on the other chromosome. Sometime later, a mutation wipes out the good gene (second hit) and growth control is lost, allowing a clone of neoplastic cells to arise. Multiple organs can be affected. Thus, familial cancers often involve more than one organ, and affected individuals can have more than one cancer, and malignancies other than epithelial are more likely (soft tissue sarcomas, leukemias/lymphomas, nervous system tumors).

The rare Li Fraumeni Syndrome illustrates the difference between "familial" and "sporadic" cancers. In Li Fraumeni syndrome there is an inherited mutation in the p53 gene, and a variety of cancers arise in persons with this mutation. However, it should be noted that p53 mutations are the most common mutations in sporadic cancers, too.