A comprehensive survey of cancer risks in extended families

Purpose: Cancer is familial; yet known cancer predisposition genes, as well as recognized environmental factors, explain only a small percentage of familial cancer clusters. This population-based description of cancer clustering describes patterns of cancer coaggregation suggestive of a genetic predisposition. Methods: Using a computerized genealogy of Utah families linked to a statewide cancer registry, we estimated the relative risks for 36 different cancer sites in first-, second-, and third-degree relatives of cancer cases, for each cancer site individually, and between cancer sites. We estimated the sex-and birth-year-specific rates for cancer using 1 million individuals in the resource. We applied these rates to groups of cases or relatives and compared the observed and expected numbers of cancers to estimate relative risks. Results: Many cancer sites show significantly elevated relative risks among distant relatives for cancer of the same site, strongly supporting a heritable contribution. Multiple combinations of cancer sites were observed among first-, second-, and third-degree relatives, suggesting the existence of heritable syndromes involving more than one cancer site. Conclusion: This complete description of coaggregation of cancer by site in a well-defined population provides a set of observations supporting heritable cancer predispositions and may support the existence of genetic factors for many different cancers.