[Genetic predisposition and radiation sensitivity of tumors]. / Genetische Prädisposition und Strahlenempfindlichkeit von Tumoren.

ABSTRACT

BACKGROUND: Studies on normal tissue radiation sensitivity have demonstrated profound differences of individual sensitivities. A number of genetic syndromes associated with abnormal radiation sensitivity have been described. Significant differences have also been detected in persons without known genetic disorders. The question arises as to whether tumors originating from normal tissues with abnormal radiation sensitivity share this abnormal sensitivity and as to whether a general correlation between normal tissue sensitivity and tumor tissue sensitivity can be substantiated. METHODS: Experimental and clinical data derived from own investigations and an extensive review of the literature was used to answer the question. RESULTS: Experimental studies on normal and tumor tissues of SCID-and C3H-mice demonstrated that the 2.7-fold enhanced radiation sensitivity of SCID normal tissues is also found in SCID tumors. Clinical investigations on cervical carcinoma and breast cancer patients revealed higher local control rates in patients with more pronounced acute side effects. A weak trend towards the same relationship was found in head and neck cancer patients. Case reports on unusually severe acute radiation side effects or unexpected tumor remissions as well as few reports on radiotherapy in ataxia telangiectasia (AT) patients suggest a correlation between normal- and tumor-tissue radiation sensitivity. Studies on fibroblasts and tumor cells from the same patient support this hypothesis in soft tissue sarcoma patients, but do not so for head and neck cancer patients. Tumor cells exhibit a considerably higher variation of radiation sensitivities than normal tissue cells. CONCLUSIONS: Experimental and clinical data are compatible with the hypothesis that normal tissue radiation sensitivity predicts for tumor tissue sensitivity. However, in view of the larger heterogeneity of tumor cell radiation sensitivity as compared to normal tissue radiation sensitivity, the development of a clinically useful predictive test for tumor sensitivity based on normal cell sensitivity appears to be unrealistic.