Amplified in breast cancer-1 glutamine repeat and prostate cancer risk

E. Platz, E. Giovannucci, Myles A. Brown, Carsta Cieluch, T. F. Shepard, M. Stampfer, P. Kantoff
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引用次数: 19

Abstract

Objectives: Amplified in breast cancer-1 (AIB1) is a steroid receptor coactivator that enhances estrogen-dependent transcriptional activation by the estrogen receptor. It is unknown whether AIB1 also interacts with the androgen receptor. Because the development and progression of prostate cancer is likely to be partially mediated by steroid hormones, we investigated whether a polymorphic CAG/CAA repeat encoding glutamine in the AIB1 gene is related to prostate cancer risk in a nested study of 581 patients and 786 age-matched control subjects in the Physicians' Health Study. Materials and Methods: DNA was extracted from peripheral whole blood, and the region encompassing the repeat was amplified using fluorescent-labeled primers. The fragments were run on polyacrylamide gels and sized by computer software. We estimated the relative risk (RR) of prostate cancer for AIB1 glutamine repeat length from logistic regression models controlling for the matching variables. Results: Three glutamine repeat lengths were prevalent: 29 (47.8% among control subjects), 28 (38.5% among control subjects), and 26 (12.6% among control subjects). Compared to 29 repeats, the RR of prostate cancer was 0.92 (95% confidence interval [CI] 0.72–1.17) for 26 repeats and 1.01 (95% CI 0.86–1.19) for 28 repeats. Compared to 28/29, the RR of prostate cancer was not significantly altered for any of the other common genotypes. No clear associations were present for AIB1 glutamine repeat length genotype by stage at the diagnosis/histologic grade of the tumor. Conclusion: This study does not support an important role in prostate cancer incidence or aggressiveness of AIB1 glutamine repeat length in the range observed in this predominately white cohort.
在乳腺癌中扩增-1谷氨酰胺重复序列和前列腺癌风险
目的:在乳腺癌中扩增的AIB1是一种类固醇受体共激活因子,可增强雌激素受体对雌激素依赖性的转录激活。目前尚不清楚AIB1是否也与雄激素受体相互作用。由于前列腺癌的发生和发展可能部分由类固醇激素介导,我们在《医师健康研究》中对581名患者和786名年龄匹配的对照组进行了巢式研究,研究了AIB1基因中编码谷氨酰胺的多态性CAG/CAA重复序列是否与前列腺癌风险相关。材料和方法:外周全血提取DNA,用荧光标记引物扩增重复序列周围区域。这些碎片在聚丙烯酰胺凝胶上运行,并通过计算机软件确定大小。我们通过控制匹配变量的逻辑回归模型估计了AIB1谷氨酰胺重复序列长度与前列腺癌的相对风险(RR)。结果:谷氨酰胺重复长度共有3种:29(对照组47.8%)、28(对照组38.5%)和26(对照组12.6%)。与29个重复相比,26个重复的前列腺癌的RR为0.92(95%可信区间[CI] 0.72-1.17), 28个重复的RR为1.01(95%可信区间[CI] 0.86-1.19)。与28/29相比,前列腺癌的RR在其他常见基因型中没有显著改变。AIB1谷氨酰胺重复序列长度基因型在肿瘤的诊断/组织学分级中没有明显的相关性。结论:本研究不支持AIB1谷氨酰胺重复序列长度在以白人为主的队列中观察到的范围内对前列腺癌发病率或侵袭性的重要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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