Malignant Neoplasms in the Families of Patients with Ataxia-Telangiectasia¹

Ataxia-telangiectasia (A-T) is an autosomal recessive syndrome associated with a greatly increased incidence of malignant neoplasms in homozygous affected individuals. Heterozygotes for the gene for A-T are thought to comprise about 1% of the general population and, therefore, it is important to know whether this gene also predisposes the heterozygous carrier to cancers. Heterozygous carriers of this gene are common among the close relatives of patients with A-T, although individual carriers cannot be identified by any clinical criterion or laboratory test. For this reason, we compared the incidence of death from malignant neoplasms in 27 families of patients with A-T to that expected in a random sample of the general population.

There were 59 deaths from malignant neoplasms in relatives dying before age 75, compared to 42.6 expected (p < 0.02). For A-T heterozygotes younger than age 45, the risk of dying from a malignant neoplasm was estimated to be greater than 5 times the risk for the general population. A-T heterozygotes may comprise more than 5% of all persons dying from a cancer before age 45.

The incidence of ovarian, gastric, and biliary system carcinomas and of leukemia and lymphoma was increased in these A-T families. Other neoplasms that may be associated with this gene in heterozygotes include pancreatic, basal cell, colonic, breast, and cervical carcinomas.