Wisconsin consanguinity studies. II: Familial adenocarcinomatosis

Predisposition to carcinoma in certain families has been recognized as an autosomal dominant trait. We describe a large pedigree (over 1,000 persons) including ten consanguineous unions with inbreeding coefficients from 0.02 to 0.17. Persons of consanguineous parentage accounted for 16 of 18 cases of adenocarcinoma (most of which were colorectal). Three women with breast cancer were relatives but not of consanguineous parentage. Only six of 36 persons with a malignancy of any kind were unrelated spouses, and only one of these had adenocarcinoma. Multiple primary carcinomas and/or early age-of-onset were observed only in products of consanguinity. In this extended family, the occurrence of adenocarcinoma appears to segregate as an autosomal recessive trait. It is conceivable that a proto-oncogene is segregating in this family and that, in some members, consanguineous unions have produced homozygosity for this oncogene.