Ataxia-telangiectasia is an autosomal recessive disease characterized by neurological and immunological symptoms, radiosensitivity and cancer predisposition. Heterozygous carriers of an ataxia-telangiectasia gene mutation are predisposed to epithelial cancers. We initiated a study to elucidate the frequency and clinical relevance of ATM gene mutations in former uranium miners exposed to high levels of radiation from radon and its decay products. Former uranium miners with Schneeberg lung cancer (n=48), former uranium miners suffering from silicosis (n=60) and uranium miners without occupational lung disorders (n=102) were investigated for nine mutations in the ATM gene. One gastric and one prostate cancer occurred in the group of miners without occupational lung diseases. Mutation analyses for S707P, IVS10-6T↷G, 2250G↷A, E1978X, R2443X, 3801delG, S49C and D2625E-A2626P were performed using genomic DNA obtained from peripheral blood samples. Three ATM gene alterations (S707P, S49C or IVS10-6T↷G) were observed. Of all cancer patients, 8.0% were heterozygous, but only 1.9% of the non-cancer controls were [OR=4.6; 95% confidence interval (CI), 0.8-26.8]. In this pilot study a major role of six ATM gene mutations could not be revealed for cancer predisposition in former uranium miners. The results leave the possibility of a moderate risk associated with more subtle ATM gene alterations.

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