血浆微 Seminoprotein-β 在前列腺癌中的作用：在欧洲癌症前瞻性调查和营养研究中的观察性巢式病例对照和孟德尔随机化研究。
The role of plasma microseminoprotein-beta in prostate cancer: an observational nested case-control and Mendelian randomization study in the European prospective investigation into cancer and nutrition.
机构信息
Cancer Epidemiology Unit.
Medical Research Council Population Health Research Unit, University of Oxford, Oxford; Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Oxford; National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospital, Oxford; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
出版信息
Ann Oncol. 2019 Jun 1;30(6):983-989. doi: 10.1093/annonc/mdz121.
BACKGROUND
Microseminoprotein-beta (MSP), a protein secreted by the prostate epithelium, may have a protective role in the development of prostate cancer. The only previous prospective study found a 2% reduced prostate cancer risk per unit increase in MSP. This work investigates the association of MSP with prostate cancer risk using observational and Mendelian randomization (MR) methods.
PATIENTS AND METHODS
A nested case-control study was conducted with the European Prospective Investigation into Cancer and Nutrition (EPIC) with 1871 cases and 1871 matched controls. Conditional logistic regression analysis was used to investigate the association of pre-diagnostic circulating MSP with risk of incident prostate cancer overall and by tumour subtype. EPIC-derived estimates were combined with published data to calculate an MR estimate using two-sample inverse-variance method.
RESULTS
Plasma MSP concentrations were inversely associated with prostate cancer risk after adjusting for total prostate-specific antigen concentration [odds ratio (OR) highest versus lowest fourth of MSP = 0.65, 95% confidence interval (CI) 0.51-0.84, Ptrend = 0.001]. No heterogeneity in this association was observed by tumour stage or histological grade. Plasma MSP concentrations were 66% lower in rs10993994 TT compared with CC homozygotes (per allele difference in MSP: 6.09 ng/ml, 95% CI 5.56-6.61, r2=0.42). MR analyses supported a potentially causal protective association of MSP with prostate cancer risk (OR per 1 ng/ml increase in MSP for MR: 0.96, 95% CI 0.95-0.97 versus EPIC observational: 0.98, 95% CI 0.97-0.99). Limitations include lack of complete tumour subtype information and more complete information on the biological function of MSP.
CONCLUSIONS
In this large prospective European study and using MR analyses, men with high circulating MSP concentration have a lower risk of prostate cancer. MSP may play a causally protective role in prostate cancer.
背景
微精囊蛋白-β（MSP）是前列腺上皮细胞分泌的一种蛋白质，可能在前列腺癌的发展中具有保护作用。之前唯一的前瞻性研究发现，MSP 每增加一个单位，前列腺癌的风险就降低 2%。本研究使用观察性和孟德尔随机化（MR）方法研究 MSP 与前列腺癌风险的关联。
患者和方法
使用欧洲癌症与营养前瞻性调查（EPIC）进行了一项巢式病例对照研究，共纳入 1871 例病例和 1871 例匹配对照。采用条件逻辑回归分析方法，研究了 MSP 与总体前列腺癌风险以及肿瘤亚型风险的相关性。使用 EPIC 数据进行估计，并结合已发表的数据，使用两样本逆方差法计算 MR 估计值。
结果
在调整总前列腺特异性抗原浓度后，血浆 MSP 浓度与前列腺癌风险呈负相关[最高与最低四分之一 MSP 的比值比（OR）=0.65，95%置信区间（CI）0.51-0.84，Ptrend=0.001]。按肿瘤分期或组织学分级观察到这种关联无异质性。与 CC 纯合子相比，rs10993994 TT 纯合子的血浆 MSP 浓度低 66%（MSP 每等位基因差异：6.09ng/ml，95%CI 5.56-6.61，r2=0.42）。MR 分析支持 MSP 与前列腺癌风险之间存在潜在的因果保护关联（MR 每增加 1ng/ml MSP 的 OR：0.96，95%CI 0.95-0.97；EPIC 观察性研究：0.98，95%CI 0.97-0.99）。局限性包括缺乏完整的肿瘤亚型信息和对 MSP 生物学功能的更完整信息。
结论
在这项大型前瞻性欧洲研究中，使用 MR 分析发现，循环 MSP 浓度较高的男性患前列腺癌的风险较低。MSP 可能在前列腺癌中发挥因果保护作用。
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