Testicular neoplasms occurring in four brothers. A search for a genetic predisposition

Four brothers who developed testicular neoplasms, one bilaterally, are described. Histologic examination showed four of the tumors to be seminomas and one to be a mixed germ cell tumor. Three of the brothers are alive. Apart from a late-onset bladder carcinoma in their father and a pulmonary cancer in a maternal uncle, cancers were not recorded in the extended kindred. One patient, a sister, and the parents had normal frequency of sister chromatid exchange (SCE) and chromosome aberrations, whereas the two patients sampled after radiation showed increase in one or both. The father was found heterozygous in 12 and the mother in 8 genetic marker systems among 25 tested. For the blood group gene loci JK and MNSs, and the erythrocyte enzyme locus GPT the father had given the same allele to all three affected sons examined. The mother had given different alleles to the sons in all of her informative markers. On the model of a recessively acting susceptibility gene, only JK and GPT remained consistent with linkage without recombination. These investigations did not add support to a genetic etiology for the unusual family occurrence of testicular cancer. An apparent birth-order effect on time at onset/diagnosis in this and published families suggests time-limited environmental factors. Nevertheless, JK, MNSs, and GPT should be included in future testis cancer families to test the model of a "dominant" genetic predisposition.