Nam Robert K, Zhang William W, Trachtenberg John, Seth Arun, Klotz Laurence H, Stanimirovic Aleksandra, Punnen Sanoj, Venkateswaran Vasundara, Toi Ants, Loblaw D Andrew, Sugar Linda, Siminovitch Katherine A, Narod Steven A
Division of Urology, Sunnybrook Research Institute, Department of Radiation Oncology, Sunnybrook Health Sciences, University of Toronto, Toronto, Ontario, Canada.
Clin Cancer Res. 2009 Mar 1;15(5):1787-93. doi: 10.1158/1078-0432.CCR-08-1593. Epub 2009 Feb 17.
Several single nucleotide polymorphisms (SNP) have been associated with the risk of prostate cancer. The clinical utility of using SNPs in the early detection of prostate cancer has not been evaluated.
We examined a panel of 25 SNPs from candidate genes and chromosomal regions in 3,004 unselected men who were screened for prostate cancer using serum prostate-specific antigen (PSA) and digital rectal examination. All underwent a prostate biopsy. We evaluated the ability of these SNPs to help predict the presence of prostate cancer at biopsy.
Of the 3,004 patients, 1,389 (46.2%) were found to have prostate cancer. Fifteen of the 25 SNPs studied were significantly associated with prostate cancer (P=0.02-7x10(-8)). We selected a combination of 4 SNPs with the best predictive value for further study. After adjusting for other predictive factors, the odds ratio for patients with all four of the variant genotypes compared with men with no variant genotype was 5.1 (95% confidence interval, 1.6-16.5; P=0.006). When incorporated into a nomogram, genotype status contributed more significantly than PSA, family history, ethnicity, urinary symptoms, and digital rectal examination (area under the curve=0.74). The positive predictive value of the PSA test ranged from 42% to 94% depending on the number of variant genotypes carried (P=1x10(-15)).
SNP genotyping can be used in a clinical setting for the early detection of prostate cancer in a nomogram approach and by improving the positive predictive value of the PSA test.
多个单核苷酸多态性（SNP）与前列腺癌风险相关。尚未评估在前列腺癌早期检测中使用SNP的临床效用。
我们检测了来自候选基因和染色体区域的一组25个SNP，检测对象为3004名未经过筛选的男性，这些男性通过血清前列腺特异性抗原（PSA）和直肠指检进行前列腺癌筛查。所有人均接受了前列腺活检。我们评估了这些SNP在活检时帮助预测前列腺癌存在与否的能力。
在3004名患者中，1389名（46.2%）被发现患有前列腺癌。所研究的25个SNP中有15个与前列腺癌显著相关（P = 0.02 - 7×10⁻⁸）。我们选择了具有最佳预测价值的4个SNP组合进行进一步研究。在调整其他预测因素后，具有所有四种变异基因型的患者与无变异基因型男性相比的优势比为5.1（95%置信区间，1.6 - 16.5；P = 0.006）。当纳入列线图时，基因型状态比PSA、家族史、种族、尿路症状和直肠指检的贡献更显著（曲线下面积 = 0.74）。PSA检测的阳性预测值根据携带的变异基因型数量在42%至94%之间（P = 1×10⁻¹⁵）。
SNP基因分型可用于临床环境，通过列线图方法以及提高PSA检测的阳性预测值来早期检测前列腺癌。
