INCIDENCE OF CANCER IN 161 FAMILIES AFFECTED BY ATAXIA-TELANGIECTASIA
INCIDENCE OF CANCER IN 161 FAMILIES AFFECTED BY ATAXIA-TELANGIECTASIA
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DOI：
10.1056/nejm199112263252602
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发表时间：
1991-12-26
影响因子：
158.5
通讯作者：
CHASE, CL
中科院分区：
文献类型：
--
作者：
SWIFT, M;MORRELL, D;CHASE, CL
背景共济失调-毛细血管扩张症是一种常染色体隐性遗传综合征，其中癌症在受影响的纯合子中的发生率比未受影响的年龄匹配受试者高约100倍。回顾性研究表明，共济失调-毛细血管扩张症基因杂合子占总人口的1%左右，也有患癌症的过度风险，特别是女性乳腺癌。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个共济失调毛细血管扩张症家族中，前瞻性地比较了1599名共济失调毛细血管扩张症患者的成年亲属和821名作为对照的配偶的癌症发病率和死亡率、缺血性心脏病死亡率以及所有原因导致的死亡率，平均时间为6.4年。在一项病例对照子研究中，我们比较了在前瞻性观察期内首次诊断为乳腺癌的19名女性血亲的职业和透视诊断辐射暴露记录，以及57名匹配的未患乳腺癌的血亲的辐射暴露记录。血亲组的癌症发病率明显高于配偶组，特别是在294名已知为共济失调-毛细血管扩张症基因杂合子的血亲亚组中。与非携带者相比，杂合子中所有类型癌症的估计风险男性为3.8，女性为3.5，女性乳腺癌为5.1。在血亲中，乳腺癌妇女比对照组更有可能暴露于选定的电离辐射源（比值比= 5.8，P = 0.005）。从20岁到59岁，男性和女性血亲的所有原因死亡率分别高出3倍和2.6倍。共济失调-毛细血管扩张基因使杂合子易患癌症，特别是女性乳腺癌。60岁以下的成年人各种原因造成的死亡率也很高。诊断性或职业性电离辐射暴露可能增加共济失调-毛细血管扩张杂合子女性患乳腺癌的风险。
Background. 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.Methods. 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.Results. 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.Conclusions. 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.