Cultured fibroblasts of 17 first-degree relatives of familial melanoma patients and six first- degree relatives of cutaneous melanoma (CMM) patients with multiple CMM primaries were tested for in vitro sensitivity to UV light. Fibroblasts of nine familial CMM patients with a known UV-sensitivity and 19 healthy probands served as a control. Sister chromatid exchange (SCE) was used as a parameter to detect UV-induced genotoxic damage. We found significantly (p < 0.001) increased UV-induced SCE levels in familial melanoma patients, as well as in first- degree relatives of familial melanoma patients (p < 0.001) after UV-A,B irradiation (375 J/m2), compared to the healthy probands without a family history of CMM. A significant (p < 0.001) increase of UV-induced SCE was also observed in the relatives of CMM patients with multiple CMM primaries. In addition, the spontaneous SCE were significantly increased (p < 0.05) in familial CMM patients. This study shows that increased UV sensitivity is a familial phenome- non. It is consistent with the concept of a genetic predisposition to CMM, which is based on
increased UV sensitivity and may help to define groups with an elevated risk of developing cutaneous malignant melanoma.