title: Molecular genotyping shows that ataxia-telangiectasia heterozygotes are predisposed to breast cancer.
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.
authors.affiliation: Institute for the Genetic Analysis of Common Diseases, New York Medical College, Hawthorne 10532, USA.
authors.forename: P
authors.initials: P
authors.lastname: Athma
authors.forename: R
authors.initials: R
authors.lastname: Rappaport
authors.forename: M
authors.initials: M
authors.lastname: Swift
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001260:Ataxia Telangiectasia / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004247:DNA / Q000097:blood; D005260:Female; D006580:Genetic Carrier Screening; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006720:Homozygote; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D016017:Odds Ratio; D011995:Recombination, Genetic
chemical_list: D005819:Genetic Markers; D004247:DNA