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Breast Cancer Incidence and the Effect of Cigarette Smoking in Heterozygous Carriers of Mutations in the Ataxia-Telangiectasia Gene

Disease Insight Research Foundation, Ardsley, New York

Requests for reprints: Michael Swift, Disease Insight Research Foundation, 410 Saw Mill River Road, Ardsley, NY 10502. Phone: 914-693-1123; Fax: 914-239-3479. E-mail: mswiftmd{at}gmail.com

Background: Mutations in the ataxia-telangiectasia (A-T) gene cause an autosomal recessive syndrome in homozygotes and compound heterozygotes and predispose female heterozygous carriers to breast cancer. No environmental agent has been previously shown to increase the risk of cancer for women who carry a mutated gene that predisposes to breast cancer. This study assesses the effect of cigarette smoking on the risk of breast cancer in A-T mutation carriers and determines age-specific and cumulative incidence rates for breast cancer among such carriers.

Methods: Clinical data were collected between 1971 and 1999 from blood relatives from 274 families of patients with A-T. The A-T mutation carrier status of 973 females was determined by molecular analysis of blood and tissue samples. The breast cancer rates in carrier smokers and nonsmokers were compared. Age-specific and cumulative breast cancer rates were also compared between carriers and noncarriers using Kaplan-Meier survival curves.

Results: The cumulative incidence through age 80 years was 80% for carriers who smoked and 21% for carriers who never smoked (P = 0.01). Six cases of breast cancer were diagnosed between ages 70 and 79 years among carriers who smoked. The cumulative breast cancer incidence among A-T mutation carriers was 43% by age 80 years, compared with 17% for noncarriers (P = 0.002). Carriers had new incident breast cancers at an annual rate of 1.4% from ages 65 through 79 years; for noncarriers the rate was 0.20%.

Conclusions: A-T carrier females had an elevated risk of breast cancer, most pronounced at older ages, compared with noncarriers, and smoking increased this risk substantially. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3188–92)