Breast Cancer Incidence and the Effect of Cigarette Smoking in Heterozygous Carriers of Mutations in the Ataxia-Telangiectasia Gene
Breast Cancer Incidence and the Effect of Cigarette Smoking in Heterozygous Carriers of Mutations in the Ataxia-Telangiectasia Gene
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DOI：
10.1158/1055-9965.epi-08-0414
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发表时间：
2008-11-01
影响因子：
3.8
通讯作者：
Lukin, Jennifer L.
中科院分区：
文献类型：
--
作者：
Swift, Michael;Lukin, Jennifer L.
背景：共济失调-毛细血管扩张症(A-T)基因突变导致纯合子和复合杂合子常染色体隐性综合征，并使女性杂合子携带者易患乳腺癌。此前没有任何环境因素被证明会增加携带易患乳腺癌突变基因的女性患癌症的风险。本研究评估吸烟对A-T突变携带者患乳腺癌风险的影响，并确定此类携带者患乳腺癌的年龄和累积发病率。方法：收集1971-1999年间274个A-T患者家族的血亲的临床数据。通过血液和组织标本的分子分析，确定973例女性的A-T突变携带者状态。比较了携带者吸烟者和不吸烟者的乳腺癌发病率。使用Kaplan-Meier生存曲线比较不同年龄和不吸烟携带者的乳腺癌累积发病率。结果：吸烟携带者80岁的累积发病率为80%，从不吸烟的携带者为21%(P=0.01)。在吸烟的携带者中，有6例在70岁至79岁之间被诊断为乳腺癌。到80岁时，A-T突变携带者的乳腺癌累积发病率为43%，而非携带者为17%(P=0.002)。从65岁到79岁，携带者每年新发乳腺癌1.4%，非携带者为0.20%。结论：与非携带者相比，A-T携带者女性患乳腺癌的风险更高，最明显的年龄段，吸烟大大增加了这一风险。(癌症流行病学生物标记物2008；17(11)：3188-92)
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)