Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Br J Cancer. 2020 Dec;123(12):1808-1817. doi: 10.1038/s41416-020-01081-3. Epub 2020 Sep 23.
Although prostate cancer is a leading cause of cancer death, its aetiology is not well understood. We aimed to identify novel biochemical factors for prostate cancer incidence and mortality in UK Biobank.
A range of cardiovascular, bone, joint, diabetes, renal and liver-related biomarkers were measured in baseline blood samples collected from up to 211,754 men at recruitment and in a subsample 5 years later. Participants were followed-up via linkage to health administrative datasets to identify prostate cancer cases. Hazard ratios (HRs) and 95% confidence intervals were calculated using multivariable-adjusted Cox regression corrected for regression dilution bias. Multiple testing was accounted for by using a false discovery rate controlling procedure.
After an average follow-up of 6.9 years, 5763 prostate cancer cases and 331 prostate cancer deaths were ascertained. Prostate cancer incidence was positively associated with circulating vitamin D, urea and phosphate concentrations and inversely associated with glucose, total protein and aspartate aminotransferase. Phosphate and cystatin-C were the only biomarkers positively and inversely, respectively, associated with risk in analyses excluding the first 4 years of follow-up. There was little evidence of associations with prostate cancer death.
We found novel associations of several biomarkers with prostate cancer incidence. Future research will examine associations by tumour characteristics.
尽管前列腺癌是癌症死亡的主要原因，但它的病因尚不清楚。我们旨在英国生物银行中确定与前列腺癌发病和死亡相关的新的生化因素。
在招募时，从多达 211754 名男性的基线血液样本中测量了一系列心血管、骨骼、关节、糖尿病、肾脏和肝脏相关的生物标志物，并在 5 年后的亚样本中进行了测量。通过与健康管理数据集的链接对参与者进行随访，以确定前列腺癌病例。使用多变量调整的 Cox 回归校正回归稀释偏差计算危险比（HR）和 95%置信区间。通过使用错误发现率控制程序来解释多重检验。
平均随访 6.9 年后，确定了 5763 例前列腺癌病例和 331 例前列腺癌死亡病例。前列腺癌的发病率与循环维生素 D、尿素和磷酸盐浓度呈正相关，与葡萄糖、总蛋白和天冬氨酸氨基转移酶呈负相关。在排除前 4 年随访的分析中，磷酸盐和半胱氨酸蛋白酶 C 是唯一与风险呈正相关和负相关的生物标志物。几乎没有证据表明与前列腺癌死亡有关。
我们发现了几种生物标志物与前列腺癌发病之间的新关联。未来的研究将通过肿瘤特征来检验这些关联。
