Association of a common AKAP9 variant with breast cancer risk:: A collaborative analysis
Association of a common AKAP9 variant with breast cancer risk:: A collaborative analysis
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DOI：
10.1093/jnci/djn037
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发表时间：
2008-03-19
期刊：
影响因子：
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通讯作者：
Burwinkel, Barbara
中科院分区：
文献类型：
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作者：
Frank, Bernd;Wiestler, Miriam;Burwinkel, Barbara
多项研究的数据表明，A 激酶锚定蛋白 (AKAP) 是信号转导的关键组成部分，其多态性有助于致癌。为了评估 AKAP 变异对乳腺癌风险的影响，我们对 6 个预计有害的非同义单核苷酸多态性进行了基因分型，并发现其中两个（M4631，1389G>T 和 N2792S，8375A>G）与德国人群中等位基因剂量依赖性家族性乳腺癌风险增加相关。我们将与 AKAP9 N2792S 存在强连锁不平衡的 AKAP9 M4631 的分析扩展到来自七项独立的欧洲和澳大利亚乳腺癌研究的 9523 名乳腺癌患者和 13770 名健康对照受试者。所有统计检验都是双面的。协作分析证实了 M4631 与乳腺癌风险增加之间的关联。在所有乳腺癌患者中，罕见等位基因 TT 纯合子（频率 = 0.19）与 GG 纯合子相比，乳腺癌的综合调整优势比 (OR) 为 1.17（95% 置信区间 [CL] = 1.08 至 1.27，P =.0003），TT 纯合子加 GT 杂合子与 GG 纯合子相比，OR 为 1.10 （95% Cl = 1.04 至 1.17，P=.001）。在 2795 名家族性乳腺癌患者的合并亚组中，各自的 OR 分别为 1.27（95% Cl = 1.12 至 1.45，P = 0.0003）和 1.16（95% Cl = 1.06 至 1.27，P = 0.001）。
Data from several studies have suggested that polymorphisms in A-kinase anchoring proteins (AKAPs), which are key components of signal transduction, contribute to carcinogenesis. To evaluate the impact of AKAP variants on breast cancer risk, we genotyped six nonsynonymous sing le-nucleotide polymorphisms that were predicted to be deleterious and found two (M4631, 1389G>T and N2792S, 8375A>G) to be associated with an allele dose-dependent increase in risk of familial breast cancer in a German population. We extended the analysis of AKAP9 M4631, which is in strong linkage disequilibrium with AKAP9 N2792S, to 9523 breast cancer patients and 13770 healthy control subjects from seven independent European and Australian breast cancer studies. All statistical tests were two-sided. The collaborative analysis confirmed the association of M4631 with increased breast cancer risk. Among all breast cancer patients, the combined adjusted odds ratio (OR) of breast cancer for individuals homozygous for the rare allele TT (frequency = 0.19) compared with GG homozygotes was 1.17 (95% confidence interval [CL] = 1.08 to 1.27, P =.0003), and the OR for TT homozygotes plus GT heterozygotes compared with GG homozygotes was 1.10 (95% Cl = 1.04 to 1.17, P=.001). Among the combined subset of 2795 familial breast cancer patients, the respective ORs were 1.27 (95% Cl = 1.12 to 1.45, P =.0003) and 1.16 (95% Cl = 1.06 to 1.27, P =.001).