Breast cancer risk in ataxia telangiectasia (AT) heterozygotes:: haplotype study in French AT families
Breast cancer risk in ataxia telangiectasia (AT) heterozygotes:: haplotype study in French AT families
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DOI：
10.1038/sj.bjc.6690460
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发表时间：
1999-06-01
影响因子：
8.8
通讯作者：
Stoppa-Lyonnet, D
中科院分区：
文献类型：
--
作者：
Janin, N;Andrieu, N;Stoppa-Lyonnet, D
共济失调毛细血管扩张 (AT) 家族的流行病学研究表明，AT 杂合子可能会增加患癌症的风险，尤其是女性患乳腺癌 (BC) 的风险。也有人提出，AT 杂合子对电离辐射影响的敏感性增加可能是 BC 风险增加的原因。本文介绍了通过 AT 儿童确定的家庭内 AT 杂合子的 BC 相对风险 (RR) 估计。收集的家庭数据包括人口特征、癌症发生情况、过去的辐射暴露和血液样本，DNA 样本使用七个 ATM 连接的微卫星标记进行研究，允许 AT 单倍型重建。使用法国估计发病率评估 BC 的相对风险。在专性 ATM 杂合子中发现 BC 风险显着增加，点估计值为 3.32 (P = 0.002)。根据年龄计算的BC相对风险在年龄小于或等于44岁的专性ATM杂合子女性亲属中显着增加（RR = 4.55，P = 0.005）。在年龄大于或等于45岁的专性ATM杂合子女性亲属中，BC相对风险在统计上处于临界状态（RR = 2.48，P = 0.08），ATM杂合子中估计的BC相对风险与之前发表的数据一致。然而，增加的风险仅比传统的生殖风险因素高一点，并且与受 BC 影响的一级亲属相关的风险相似。
Epidemiological studies in ataxia telangiectasia (AT) families have suggested that AT heterozygotes could have an increased cancer risk, especially breast cancer (BC) in women. It has also been suggested that an increased sensibility of AT heterozygotes to the effect of ionizing radiation could be responsible for the increased BC risk. BC relative risk (RR) estimation in AT heterozygotes within families ascertained through AT children is presented here. Family data collected included demographic characteristics, occurrence of cancers, past radiation exposures and blood samples, DNA samples were studied using seven ATM linked microsatellites markers allowing AT haplotypes reconstitution. The relative risk of BC was assessed using French estimated incidence rates. A significant increase risk of BC is found among obligate ATM heterozygotes with a point estimate of 3.32 (P = 0.002). BC relative risk calculated according to age is significantly increased among the obligate ATM heterozygotes female relatives with an age less than or equal to 44 years (RR = 4.55, P = 0.005). The BC relative risk is statistically borderline among the obligate ATM heterozygote female relatives with an age greater than or equal to 45 years (RR = 2.48, P= 0.08), The estimated BC relative risk among ATM heterozygotes is consistent with previously published data. However, the increased risk is only a little higher than classical reproductive risk factors and similar to the risk associated with a first-degree relative affected by BC.