Liu Xin, Cicek Mine S, Plummer Sarah J, Jorgenson Eric, Casey Graham, Witte John S
Department of Epidemiology and Biostatistics, and Institute for Human Genetics, University of California, San Francisco, San Francisco, California 94143-0794, USA.
J Urol. 2007 Mar;177(3):894-8. doi: 10.1016/j.juro.2006.10.057.
The testis derived transcript gene has been suggested as a tumor suppressor gene for prostate cancer at 7q31. To investigate this concept we evaluated the effects of 7 tagging single nucleotide polymorphisms that comprehensively captured the common genetic variants in TES on aggressive prostate cancer in a case-control study.
A total of 506 cases diagnosed with aggressive prostate cancer, and an equal number of age, institute and ethnicity matched controls, were recruited from the major medical institutions in Cleveland, Ohio. A logistic regression model was used to evaluate the association between SNPs/multimarker haplotypes and prostate cancer.
When looking at all study subjects and white men only, no statistically significant associations were observed between any variants and more aggressive disease. However, 3 variants showed inverse associations with disease in black men (178), including 2 intronic SNPs (rs2402056, rs1004109) and 1 SNP close to the 3' untranslated region (rs4730721) with ORs of 0.57 (95% CI 0.36-0.90, under an additive mode of inheritance), 0.57 (95% CI 0.36-0.91, under an additive mode of inheritance) and 0.45 (95% CI 0.21-0.98, under a dominant mode of inheritance), respectively. Variants rs2402056 and rs1004109 are in tight linkage disequilibrium (r2=0.8) and the reconstructed haplotype did not provide any additional evidence for association than their genotype level results.
Our findings suggest that the variants in TES, or in a nearby gene, may be associated with prostate cancer in black men.
睾丸衍生转录本基因被认为是位于7q31的前列腺癌抑癌基因。为了研究这一概念，我们在一项病例对照研究中评估了7个标签单核苷酸多态性对侵袭性前列腺癌的影响，这些多态性全面捕获了睾丸衍生转录本基因（TES）中的常见遗传变异。
从俄亥俄州克利夫兰的主要医疗机构招募了总共506例被诊断为侵袭性前列腺癌的病例，以及数量相等的年龄、机构和种族匹配的对照。使用逻辑回归模型评估单核苷酸多态性/多标记单倍型与前列腺癌之间的关联。
在查看所有研究对象以及仅白人男性时,未观察到任何变异与侵袭性更强的疾病之间存在统计学上的显著关联。然而，3个变异在黑人男性（178例）中显示出与疾病的反向关联，包括2个内含子单核苷酸多态性（rs2402056、rs1004109）和1个靠近3'非翻译区的单核苷酸多态性（rs4730721），其优势比分别为0.57（95%可信区间0.36 - 0.90，在加性遗传模式下）、0.57（95%可信区间0.36 - 0.91，在加性遗传模式下）和0.45（95%可信区间0.21 - 0.98，在显性遗传模式下）。单核苷酸多态性rs2402056和rs1004109处于紧密连锁不平衡状态（r2 = 0.8），重建的单倍型没有比其基因型水平结果提供更多的关联证据。
我们的研究结果表明，睾丸衍生转录本基因（TES）或其附近基因中的变异可能与黑人男性的前列腺癌有关。
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