Genetics of SV40 T-antigen expression: studies of twins, heritable syndromes and cancer families.

Susceptibility of human skin fibroblasts to SV40 virus infection has been suggested as a marker of cancer risk. To evaluate the role of heritable factors in the regulation of SV40 T-antigen, fibroblasts from 9 pairs of identical twins and 129 members of cancer-prone families, including 16 with cancer, were tested in a 3-day immunofluorescence assay. In the twin study, the variance of T-antigen values was significantly less in identical than in fraternal or non-twin sibs, suggesting a heritable component in the regulation of SV40 infection. In the families, T-antigen values of parents and children were compared to models of Mendelian inheritance. At least three modes of inheritance--autosomal dominant, recessive, and X-linker--were observed. The distribution of offspring values compared to those of their parents suggested that interaction of multiple genetic factors influences the T-antigen value in individual patients. With the exception of Fanconi's anemia, the values for patients with cancer or predisposing syndromes were not uniformly elevated. The utility of this assay as a marker of cancer risk appears limited because of the complexity of factors that influence T-antigen expression in individual cases.