Centre for BioinformaticsBiomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia Priority Research Centre for CancerSchool of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia.
Centre for Clinical Epidemiology and BiostatisticsSchool of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia Clinical Research DesignIT and Statistical Support Unit, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
Endocr Connect. 2016 May;5(3):115-22. doi: 10.1530/EC-16-0003. Epub 2016 Apr 18.
Due to the lack of high-throughput genetic assays for tandem repeats, there is a paucity of knowledge about the role they may play in disease. A polymorphic CA repeat in the promoter region of the insulin-like growth factor 1 gene (IGF1 has been studied extensively over the past 10 years for association with the risk of developing breast cancer, among other cancers, with variable results. The aim of this study was to determine if this CA repeat is associated with the risk of developing breast cancer and endometrial cancer. Using a case-control design, we analysed the length of this CA repeat in a series of breast cancer and endometrial cancer cases and compared this with a control population. Our results showed an association when both alleles were considered in breast and endometrial cancers (P=0.029 and 0.011, respectively), but this did not pass our corrected threshold for significance due to multiple testing. When the allele lengths were analysed categorically against the most common allele length of 19 CA repeats, an association was observed with the risk of endometrial cancer due to a reduction in the number of long alleles (P=0.013). This was confirmed in an analysis of the long alleles separately for endometrial cancer risk (P=0.0012). Our study found no association between the length of this polymorphic CA repeat and breast cancer risk. The significant association observed between the CA repeat length and the risk of developing endometrial cancer has not been previously reported.
由于缺乏用于串联重复的高通量遗传检测方法，因此对于它们在疾病中可能发挥的作用知之甚少。过去 10 年来，胰岛素样生长因子 1 基因（IGF1）启动子区域的一个多态性 CA 重复序列已被广泛研究，以探讨其与乳腺癌和其他癌症的发病风险之间的关联，但结果存在差异。本研究旨在确定该 CA 重复序列是否与乳腺癌和子宫内膜癌的发病风险相关。我们采用病例对照设计，分析了一系列乳腺癌和子宫内膜癌病例中该 CA 重复序列的长度，并将其与对照人群进行了比较。我们的结果表明，当同时考虑两个等位基因时，CA 重复序列与乳腺癌和子宫内膜癌均存在关联（P=0.029 和 0.011），但由于多次检验，这并未通过我们校正后的显著性阈值。当根据最常见的 19 个 CA 重复等位基因长度对等位基因长度进行分类分析时，观察到与子宫内膜癌风险相关的等位基因长度降低（P=0.013）。对子宫内膜癌风险的长等位基因单独分析也证实了这一点（P=0.0012）。本研究未发现该多态性 CA 重复序列长度与乳腺癌风险之间存在关联。CA 重复序列长度与子宫内膜癌发病风险之间存在显著关联，这在以前的研究中尚未报道过。
