Cancer risks in A-T heterozygotes.
It is well established that ataxia-telangiectasia (A-T) patients suffer a grossly elevated risk of cancer, particularly lymphoma and leukaemia, but the possibility of an excess cancer risk of cancer in heterozygotes carriers of A-T mutations is more controversial. A number of studies indicate that female relatives of A-T patients suffer excess risk of breast cancer; based on an overview of all currently available data the estimated relative risk of breast cancer to A-T heterozygotes is 3.9-fold (95% CI 2.1-7.2). There is some suggestion that relative risk declines with age. In contrast, there is no consistent evidence of a risk from any other cancer; the estimated risk from all studies is 1.9 (95% CI 1.5-2.5) but some studies show a larger effect whilst others show no excess risk. On the basis of these results and the likely frequency of the A-T gene, A-T heterozygotes would account for between 1 and 13% of breast cancer cases, with 3.8% being the best estimate. However, unless the breast cancer risk has been seriously underestimated, the A-T gene will make little contribution to familial breast cancer.
Section of Epidemiology, Institute of Cancer Research, Belmont, UK.
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Easton
D000328:Adult; D000368:Aged; D001260:Ataxia Telangiectasia / Q000150:complications* / Q000235:genetics*; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D005192:Family Health; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology