Study design: evaluating gene-environment interactions in the etiology of breast cancer - the WECARE study.
Study design: evaluating gene-environment interactions in the etiology of breast cancer - the WECARE study.
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DOI：
10.1186/bcr771
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
WECARE study
中科院分区：
文献类型：
--
作者：
Bernstein JL;Langholz B;Haile RW;Bernstein L;Thomas DC;Stovall M;Malone KE;Lynch CF;Olsen JH;Anton-Culver H;Shore RE;Boice JD Jr;Berkowitz GS;Gatti RA;Teitelbaum SL;Smith SA;Rosenstein BS;Børresen-Dale AL;Concannon P;Thompson WD;WECARE study
细胞对DNA损伤的反应缺陷可能易患癌症。电离辐射可导致细胞簇损伤和双链断裂（DSB），从而给细胞修复过程带来问题。三个基因（ATM，BRCA 1和BRCA 2）编码的产物是正常细胞对DSB反应所必需的，但突变时易患乳腺癌。为了研究辐射暴露和遗传易感性在乳腺癌病因学中的联合作用，我们设计了一项病例对照研究，该研究嵌套在五个基于人群的癌症登记处中。我们假设在这些基因中携带突变等位基因的女性比非携带者更容易患辐射诱发的乳腺癌。在我们的研究中，700名患有非同步双侧乳腺癌的女性与1400名患有单侧乳腺癌的对照者在首次乳腺癌诊断的日期和年龄、种族和登记区域方面进行了单独匹配，并在放射治疗方面进行了反向匹配。每个三联体包括两名接受放射治疗的妇女和一名没有接受放射治疗的妇女。采用综合剂量重建方法估计初始治疗后对侧乳房的辐射吸收剂量，该方法包括应用患者治疗参数在拟人和水模型中进行实验测量。从所有参与者中采集血液样本进行遗传分析。我们的研究设计提高了检测基因-环境相互作用的疾病时，基因突变和感兴趣的环境暴露在一般人群中是罕见的潜力。这是特别适用于双侧乳腺癌的研究，因为辐射剂量和遗传易感性具有重要的病因作用，可能是通过相互作用的机制。通过使用反匹配，我们通过增加病例对照组内辐射剂量的变异性来优化收集的剂量测定数据的信息量，并增强我们检测辐射-基因型相互作用的能力。
Deficiencies in cellular responses to DNA damage can predispose to cancer. Ionizing radiation can cause cluster damage and double-strand breaks (DSBs) that pose problems for cellular repair processes. Three genes (ATM, BRCA1, and BRCA2) encode products that are essential for the normal cellular response to DSBs, but predispose to breast cancer when mutated. To examine the joint roles of radiation exposure and genetic susceptibility in the etiology of breast cancer, we designed a case-control study nested within five population-based cancer registries. We hypothesized that a woman carrying a mutant allele in one of these genes is more susceptible to radiation-induced breast cancer than is a non-carrier. In our study, 700 women with asynchronous bilateral breast cancer were individually matched to 1400 controls with unilateral breast cancer on date and age at diagnosis of the first breast cancer, race, and registry region, and counter-matched on radiation therapy. Each triplet comprised two women who received radiation therapy and one woman who did not. Radiation absorbed dose to the contralateral breast after initial treatment was estimated with a comprehensive dose reconstruction approach that included experimental measurements in anthropomorphic and water phantoms applying patient treatment parameters. Blood samples were collected from all participants for genetic analyses. Our study design improves the potential for detecting gene–environment interactions for diseases when both gene mutations and the environmental exposures of interest are rare in the general population. This is particularly applicable to the study of bilateral breast cancer because both radiation dose and genetic susceptibility have important etiologic roles, possibly by interactive mechanisms. By using counter-matching, we optimized the informativeness of the collected dosimetry data by increasing the variability of radiation dose within the case–control sets and enhanced our ability to detect radiation–genotype interactions.
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影响因子：
56.9
作者：
Cortez, D;Wang, Y;Elledge, SJ
通讯作者：
Elledge, SJ
影响因子：
10.4
作者：
Langholz B;Clayton D
通讯作者：
Clayton D
影响因子：
5.5
作者：
JOHN, EM;KELSEY, JL
通讯作者：
KELSEY, JL
影响因子：
4.7
作者：
Cologne, J;Langholz, B
通讯作者：
Langholz, B
影响因子：
3.9
作者：
Bernstein, JL;Teraoka, S;Concannon, P
通讯作者：
Concannon, P