alexa Molecular genotyping shows that ataxia-telangiectasia heterozygotes are predisposed to breast cancer.
Oncology

Oncology

Journal of Cancer Science & Therapy

Author(s): Athma P, Rappaport R, Swift M

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Abstract About 1.4\% of the general population are heterozygous carriers of the gene for ataxiatelangiectasia (A-T), an autosomal recessive progressive neurologic syndrome in which cancer incidence of homozygotes is approximately 100-fold greater than the general population's rates. The hypothesis that A-T heterozygotes are predisposed to breast cancer was tested by the unbiased statistically powerful index-test method based on molecular genotyping. The A-T gene carrier status of 775 blood relatives in 99 A-T families was determined by tracing the A-T gene in each family through tightly linked flanking DNA markers. There were 33 women with breast cancer who could be genotyped; 25 of these were A-T heterozygotes, compared to an expected 14.9 (odds ratio 3.8, 95\% confidence limits 1.7-8.4, one-sided p = .0001). This demonstrates that the A-T gene predisposes heterozygotes to breast cancer. For the 21 breast cancers with onset before age 60, the odds ratio was 2.9 (1.1-7.6, p = .009) and for the 12 cases with onset at age 60 or older, the odds ratio was 6.4 (1.4-28.8, p = .002). Thus the breast cancer risk for A-T heterozygous women is not limited to young women but appears even higher at older ages. Of all breast cancers in the United States, 6.6\% may occur in women who are A-T heterozygotes. This proportion is several fold greater than the estimated proportion of carriers of BRCA1 mutations in breast cancer cases with onset at any age.
This article was published in Cancer Genet Cytogenet and referenced in Journal of Cancer Science & Therapy

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