He Chiyu, Qian Yu, Liu Bin, Yang Shaoxue, Ye Ding, Sun Xiaohui, Chen Tianhui, Mao Yingying
Second College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.
School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Front Oncol. 2020 Oct 14;10:545603. doi: 10.3389/fonc.2020.545603. eCollection 2020.
Inconsistent findings from observational studies have reported that C-reactive protein (CRP) is likely associated with risk of prostate cancer. Because conventional observational studies are susceptible to confounding and reverse causality, it remains unclear whether there is a causal relationship of CRP with risk of prostate cancer.
In this study, we applied a two-sample Mendelian randomization (MR) approach to evaluate the potential causal association of circulating CRP levels with prostate cancer risk. Instrumental variables (IVs) and corresponding genetic association estimates for circulating CRP levels were obtained from a meta-analysis of genome-wide association studies (GWASs) including 204,402 participants of European descent. The genetic association estimates of these IVs with prostate cancer were obtained from a GWAS meta-analysis including 79,148 cases and 61,106 controls of European ancestry. The inverse-variance weighted (IVW) method was used as primary MR analyses, whereas in sensitivity analyses, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO) test were used to assess the presence of pleiotropy. Odd ratio (OR) and 95% CI were calculated.
Overall, 58 single-nucleotide polymorphisms were used as instruments for circulating CRP levels. MR analysis suggested that genetically determined CRP levels were not associated with prostate cancer risk (OR 1.06, 95% CI 0.96 to 1.16) using the IVW method. Sensitivity analyses using alternative MR methods produced similar results (OR 1.00, 95% CI 0.93 to 1.08 for the weighted-median method; OR 1.02, 95% CI 0.95 to 1.08 for MR-PRESSO test). MR-Egger regression did not suggest evidence of directional pleiotropy ( = 0.25).
Our study found that genetically predicted circulating CRP levels were not associated with prostate cancer risk, suggesting that CRP is unlikely to be a causal factor in the development of prostate cancer.
观察性研究结果不一致，报告称C反应蛋白（CRP）可能与前列腺癌风险相关。由于传统的观察性研究易受混杂因素和反向因果关系的影响，CRP与前列腺癌风险之间是否存在因果关系仍不清楚。
在本研究中，我们应用两样本孟德尔随机化（MR）方法来评估循环CRP水平与前列腺癌风险之间的潜在因果关联。循环CRP水平的工具变量（IVs）和相应的基因关联估计值来自对包括204,402名欧洲血统参与者的全基因组关联研究（GWASs）的荟萃分析。这些IVs与前列腺癌的基因关联估计值来自对包括79,148例病例和61,106例欧洲血统对照的GWAS荟萃分析。采用逆方差加权（IVW）方法作为主要的MR分析，而在敏感性分析中，使用MR-Egger回归和MR多效性残差和异常值（MR-PRESSO）检验来评估多效性的存在。计算比值比（OR）和95%置信区间（CI）。
总体而言，58个单核苷酸多态性被用作循环CRP水平的工具。MR分析表明，使用IVW方法，基因决定的CRP水平与前列腺癌风险无关（OR 1.06，95% CI 0.96至1.16）。使用替代MR方法的敏感性分析产生了类似的结果（加权中位数方法的OR 1.00，95% CI 0.93至1.08；MR-PRESSO检验的OR 1.02，95% CI 0.95至1.08）。MR-Egger回归未提示定向多效性的证据（ = 0.25）。
我们的研究发现，基因预测的循环CRP水平与前列腺癌风险无关，这表明CRP不太可能是前列腺癌发生中的因果因素。
