Zhan Yongle, Ruan Xiaohao, Liu Jiacheng, Huang Da, Huang Jingyi, Huang Jinlun, Chun Tsun Tsun Stacia, Ng Ada Tsui-Lin, Wu Yishuo, Wei Gonghong, Jiang Haowen, Xu Danfeng, Na Rong
Division of Urology, Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Cancers (Basel). 2023 May 8;15(9):2650. doi: 10.3390/cancers15092650.
Telomerase reverse transcriptase () has been consistently associated with prostate cancer (PCa) risk. However, few studies have explored the association between variants and PCa aggressiveness.
Individual and genetic data were obtained from UK Biobank and a Chinese PCa cohort (Chinese Consortium for Prostate Cancer Genetics).
A total of 209,694 Europeans (14,550 PCa cases/195,144 controls) and 8873 Chinese (4438 cases/4435 controls) were involved. Nineteen susceptibility loci with five novel ones (rs144704378, rs35311994, rs34194491, rs144020096, and rs7710703) were detected in Europeans, whereas seven loci with two novel ones (rs7710703 and rs11291391) were discovered in the Chinese cohort. The index SNP for the two ancestries was rs2242652 (odds ratio [OR] = 1.16, 95% confidence interval [CI]:1.12-1.20, = 4.12 × 10) and rs11291391 (OR = 1.73, 95%CI:1.34-2.25, = 3.04 × 10), respectively. SNPs rs2736100 (OR = 1.49, 95%CI:1.31-1.71, = 2.91 × 10) and rs2853677 (OR = 1.74, 95%CI:1.52-1.98, = 3.52 × 10) were found significantly associated with aggressive PCa, while rs35812074 was marginally related to PCa death (hazard ratio [HR] = 1.61, 95%CI:1.04-2.49, = 0.034). Gene-based analysis showed a significant association of with PCa (European: = 3.66 × 10, Chinese: = 0.043) and PCa severity ( = 0.006) but not with PCa death ( = 0.171).
polymorphisms were associated with prostate tumorigenesis and severity, and the genetic architectures of PCa susceptibility loci were heterogeneous among distinct ancestries.
端粒酶逆转录酶（）一直与前列腺癌（PCa）风险相关。然而，很少有研究探讨基因变异与PCa侵袭性之间的关联。
从英国生物银行和一个中国PCa队列（中国前列腺癌遗传学联盟）获取个体和基因数据。
共纳入209,694名欧洲人（14,550例PCa病例/195,144例对照）和8873名中国人（4438例病例/4435例对照）。在欧洲人中检测到19个易感位点，其中5个为新位点（rs144704378、rs35311994、rs34194491、rs144020096和rs7710703），而在中国队列中发现7个位点，其中2个为新位点（rs7710703和rs11291391）。两个祖先群体的索引单核苷酸多态性（SNP）分别为rs2242652（优势比[OR]=1.16，95%置信区间[CI]：1.12 - 1.20，=4.12×10）和rs11291391（OR = 1.73，95%CI：1.34 - 2.25，=3.04×10）。SNP rs2736100（OR = 1.49，95%CI：1.31 - 1.71，=2.91×10）和rs2853677（OR = 1.74，95%CI：1.52 - 1.98，=3.52×10）被发现与侵袭性PCa显著相关，而rs35812074与PCa死亡有边缘相关性（风险比[HR]=1.61，95%CI：1.04 - 2.49，=0.034）。基于基因的分析显示与PCa（欧洲人：=3.66×10，中国人：=0.043）和PCa严重程度（=0.006）显著相关，但与PCa死亡无关（=0.171）。
基因多态性与前列腺肿瘤发生和严重程度相关，且PCa易感位点的遗传结构在不同祖先群体中存在异质性。
