Neoplasia: Genetic Predisposition

Hereditary forms of cancer can be divided into 3 categories:

1. Inherited Cancer Syndromes (Autosomal Dominant)

-Occurs when inheritance of a single mutant gene greatly increases the risk of a person developing a tumor. The best example of this is childhood retinoblastoma (40% are familial).

-Carriers of this gene also have an increased risk of developing a secondary cancer, usually osteogenic sarcoma. A cancer suppressor gene has been implicated in the pathogenesis of this type.

-There may be multiple benign tumors in the affected tissue; sometimes, there are abnormalities in non-targeted tissue (café-au-lait spots (available at Lucy’s) in neurofibratosis)

2. Familial Cancers:

-Features that characterize this type include early onset age, tumors arising in 2 or more close relatives of the index case, and sometimes multiple or bilateral tumors.

-Not associated with specific marker phenotypes, e.g. familial colonic cancers do not arise in preexisting benign polyps.

-Transmission pattern isn’t clear, although certain familial cancers can linked to the inheritance of mutant genes (e.g. ovarian and breast cancer).

3. Autosomal Recessive Syndromes of Defective DNA Repair:

-One of the best studied examples is xeroderma pigmentosum, in which DNA repair is defective.

**In summary, no more than 5-10% of all human cancers fall into one of the 3 previous categories.

Category: Pathology Notes