Swift M, Morrell D, Massey R B, Chase C L
Biological Sciences Research Center, University of North Carolina, Chapel Hill 27599-7250.
N Engl J Med. 1991 Dec 26;325(26):1831-6. doi: 10.1056/NEJM199112263252602.
Ataxia-telangiectasia is an autosomal recessive syndrome in which cancers develop in affected homozygotes at a rate approximately 100 times higher than in unaffected age-matched subjects. Retrospective studies have shown that persons heterozygous for the ataxia-telangiectasia gene, who make up about 1 percent of the general population, also have an excess risk of cancer, particularly breast cancer in women. Patients with ataxia-telangiectasia and cells derived from homozygotes and heterozygotes are unusually sensitive to ionizing radiation.
Cancer incidence and mortality, mortality from ischemic heart disease, and mortality from all causes were compared prospectively for a mean of 6.4 years in 1599 adult blood relatives of patients with ataxia-telangiectasia and 821 of their spouses, who served as controls, in 161 families affected by ataxia-telangiectasia. In a case-control substudy, we compared documented occupational and fluoroscopic diagnostic exposures to radiation in the 19 female blood relatives in whom breast cancer was first diagnosed during the period of prospective observation with the exposures in 57 matched blood relatives who did not have breast cancer.
Cancer rates were significantly higher in the group of blood relatives than in their spouses, specifically in the subgroup of 294 blood relatives who were known to be heterozygous for the ataxia-telangiectasia gene. The estimated risk of cancer of all types among heterozygotes as compared with noncarriers was 3.8 in men and 3.5 in women, and that for breast cancer in women was 5.1. Among the blood relatives, women with breast cancer were more likely to have been exposed to selected sources of ionizing radiation than controls without cancer (odds ratio = 5.8, P = 0.005). Male and female blood relatives also had 3-fold and 2.6-fold excess mortality from all causes, respectively, from the ages of 20 through 59 years.
The ataxia-telangiectasia gene predisposes heterozygotes to cancer, particularly breast cancer in women. There is also excess mortality from all causes in adults under the age of 60. Diagnostic or occupational exposure to ionizing radiation probably increases the risk of breast cancer in women heterozygous for ataxia-telangiectasia.
共济失调毛细血管扩张症是一种常染色体隐性综合征，患病纯合子患癌症的几率比年龄匹配的未患病者高约100倍。回顾性研究表明，共济失调毛细血管扩张症基因的杂合子人群（约占总人口的1%）患癌症的风险也更高，尤其是女性乳腺癌。共济失调毛细血管扩张症患者以及来自纯合子和杂合子的细胞对电离辐射异常敏感。
在161个受共济失调毛细血管扩张症影响的家庭中，对1599名共济失调毛细血管扩张症患者的成年血亲及其821名配偶（作为对照）进行了平均6.4年的前瞻性比较，比较内容包括癌症发病率和死亡率、缺血性心脏病死亡率以及全因死亡率。在一项病例对照子研究中，我们比较了在前瞻性观察期间首次诊断出乳腺癌的19名女性血亲与57名未患乳腺癌的匹配血亲的职业和荧光透视诊断辐射暴露记录。
血亲组的癌症发病率显著高于其配偶组，特别是在已知为共济失调毛细血管扩张症基因杂合子的294名血亲亚组中。与非携带者相比，杂合子男性患各类癌症的估计风险为3.8，女性为3.5，女性患乳腺癌的风险为5.1。在血亲中，患乳腺癌的女性比未患癌症的对照者更有可能接触特定的电离辐射源（优势比=5.8，P=0.005）。在20至59岁年龄段，男性和女性血亲的全因死亡率也分别高出3倍和2.6倍。
共济失调毛细血管扩张症基因使杂合子易患癌症，尤其是女性乳腺癌。60岁以下成年人的全因死亡率也较高。诊断性或职业性电离辐射暴露可能会增加共济失调毛细血管扩张症基因杂合子女性患乳腺癌的风险。
