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

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Abstract
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‐linked—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.