Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA.
Prostate. 2024 Nov;84(15):1355-1365. doi: 10.1002/pros.24774. Epub 2024 Aug 15.
Multiple novel protein biomarkers have been shown to be associated with prostate cancer risk using genetic instruments. This study aimed to externally validate the associations of 30 genetically predicted candidate proteins with prostate cancer risk using aptamer-based levels in US Black and White men in the Atherosclerosis Risk in Communities (ARIC) study. Plasma protein levels were previously measured by SomaScan® using the blood collected in 1990-1992.
Among 4864 eligible participants, we ascertained 667 first primary prostate cancer cases through 2015. Hazard ratios (HRs) of prostate cancer and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression for tertiles of each protein. We adjusted for age, race, and other risk factors.
Of the 30 proteins and considering a nominal p trend < 0.05, two were positively associated with prostate cancer risk-RF1ML (tertile 3 vs. 1: HR = 1.23; 95% CI 1.02-1.48; p trend = 0.037) and TPST1 (1.28, 95% CI 1.06-1.55; p trend = 0.0087); two were inversely associated-ATF6A (HR = 0.80, 95% CI 0.65-0.98; p trend = 0.028) and SPINT2 (HR = 0.74, 95% CI 0.61-0.90; p trend = 0.0025). One protein, KDEL2, which was nonlinearly associated (test-for-linearity: p < 0.01) showed a statistically significant lower risk in the second tertile (HR = 0.79, 95% CI 0.65-0.95). Of these five, four proteins-ATF6A, KDEL2, RF1ML, and TPST1-were consistent in the direction of association with the discovery studies.
This study validated some pre-diagnostic protein biomarkers of the risk of prostate cancer.
多项新的蛋白质生物标志物已被证明与使用遗传工具的前列腺癌风险相关。本研究旨在通过美国黑人和白人男性的动脉粥样硬化风险社区（ARIC）研究中的基于适体的水平，对 30 种经遗传预测的候选蛋白与前列腺癌风险的关联进行外部验证。在 1990-1992 年采集的血液中，使用 SomaScan® 之前测量了血浆蛋白水平。
在 4864 名合格参与者中，我们通过 2015 年确定了 667 例首次原发性前列腺癌病例。使用 Cox 比例风险回归估计了每个蛋白质三分位的前列腺癌风险的风险比（HR）和 95%置信区间（CI）。我们调整了年龄、种族和其他风险因素。
在 30 种蛋白质中，考虑到名义 p 趋势<0.05，有两种与前列腺癌风险呈正相关-RF1ML（三分位 3 与 1 相比：HR=1.23；95%CI 1.02-1.48；p 趋势=0.037）和 TPST1（1.28，95%CI 1.06-1.55；p 趋势=0.0087）；两种呈负相关-ATF6A（HR=0.80，95%CI 0.65-0.98；p 趋势=0.028）和 SPINT2（HR=0.74，95%CI 0.61-0.90；p 趋势=0.0025）。一种蛋白质 KDEL2 呈非线性相关（检验线性：p<0.01），在第二三分位显示出统计学上较低的风险（HR=0.79，95%CI 0.65-0.95）。在这五个中，有四个蛋白质-ATF6A、KDEL2、RF1ML 和 TPST1-与发现研究的关联方向一致。
本研究验证了一些前列腺癌风险的预诊断蛋白质生物标志物。
