Laboratory of Cancer Genetics, Institute of Medical Technology and Centre of Laboratory Medicine, University of Tampere and Tampere University Hospital, Biokatu 8, FI-33014 Tampere, Finland.
Int J Cancer. 2011 Aug 1;129(3):599-606. doi: 10.1002/ijc.25754. Epub 2011 Jan 6.
Prostate cancer is the most frequently diagnosed cancer in men; however, the genetic basis of susceptibility remains elusive. The EMSY gene is located in the prostate cancer linked chromosome region at 11q13.5. The aim of this study was to screen EMSY for sequence variants and to evaluate its association with the risk of prostate cancer. We performed a Finnish population-based case-control study with 923 controls, 184 familial prostate cancer cases and 2,301 unselected prostate cancer cases. Variants were screened using sequencing and validated using the TaqMan assay and High Resolution Melting analysis. A total of 27 sequence variants were found, and 17 of them were novel. A rare intronic variant, IVS6-43A>G (minor allele frequency of 0.004), increased the prostate cancer risk in familial cases (odds ratio [OR] = 7.5; 95% confidence interval [CI] = 1.3-45.5; p = 0.02). Further analysis with clinicopathological data revealed that the variant is associated with aggressive unselected cases (prostate specific antigen ≥ 20 μg/L or Gleason grade ≥ 7), based on both case-control (OR = 6.0; 95% CI = 1.3-26.4; p = 0.03) and case-case analyses (OR = 6.5; 95% CI = 1.5-28.4; p = 0.002). In addition, all variant-positive familial cases had aggressive cancer. Our results indicate that the intronic variant IVS6-43A>G increases the familial and unselected prostate cancer risk in a Finnish population and contributes to the aggressive progression of the disease in a high-penetrance manner. The potential role of the variant as a predictive genetic marker for aggressive prostate cancer should be further evaluated.
前列腺癌是男性中最常见的癌症；然而，其易感性的遗传基础仍然难以捉摸。EMSY 基因位于 11q13.5 的前列腺癌相关染色体区域。本研究旨在筛选 EMSY 的序列变异，并评估其与前列腺癌风险的关联。我们进行了一项基于芬兰人群的病例对照研究，共有 923 名对照、184 例家族性前列腺癌病例和 2301 例非选择性前列腺癌病例。使用测序筛选变体，并使用 TaqMan 测定法和高分辨率熔解分析进行验证。共发现 27 个序列变异，其中 17 个是新的。一个罕见的内含子变异，IVS6-43A>G（次要等位基因频率为 0.004），增加了家族性病例的前列腺癌风险（比值比 [OR] = 7.5；95%置信区间 [CI] = 1.3-45.5；p = 0.02）。进一步的临床病理数据分析表明，该变体与侵袭性非选择性病例（前列腺特异性抗原≥20μg/L 或 Gleason 分级≥7）相关，这是基于病例对照（OR=6.0；95%CI=1.3-26.4；p=0.03）和病例病例分析（OR=6.5；95%CI=1.5-28.4；p=0.002）。此外，所有变体阳性的家族性病例均患有侵袭性癌症。我们的研究结果表明，内含子变异 IVS6-43A>G 增加了芬兰人群中的家族性和非选择性前列腺癌风险，并以高外显率方式促进疾病的侵袭性进展。该变体作为侵袭性前列腺癌预测遗传标志物的潜在作用应进一步评估。
