Chen Peixian, Wang Yue, Xiong Zhi, Luo Tianlong, Lai Yiming, Zhong Haitao, Peng Shirong, Zhuang Ruilin, Li Kaiwen, Huang Hai
Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China.
National Institutes for Food and Drug Control, Beijing 102629, China.
Cancer Pathog Ther. 2024 Mar 29;2(4):292-298. doi: 10.1016/j.cpt.2024.03.002. eCollection 2024 Oct.
Although many epidemiological studies and meta-analyses have reported an association between autoimmune disorders and prostate cancer, none has reported a clear correlation or the direction of the association. The purpose of our study was to explore the potential relationship between autoimmunity-related disorders and prostate cancer using Mendelian randomization (MR).
We retrieved literature from PubMed using the keywords "autoimmune disorder" AND "prostate cancer" to find more clues on the correlation between prostate cancer and autoimmunity-related disorder. Based on this literature search, we selected 16 autoimmunity-related disorders that had genome-wide association study (GWAS) data and may be associated with prostate cancer. The inverse variance weighting (IVW) method was applied as our primary analysis for two-sample MR and multivariate MR analysis to estimate the odds ratio (OR) and 95% confidence interval (CI). We further verified the robustness of our conclusions using a series of sensitivity analyses.
The autoimmunity-related diseases selected include rheumatoid arthritis, ankylosing spondylitis, coxarthrosis, gonarthrosis, Crohn's disease, ulcerative colitis, irritable bowel syndrome, celiac disease, primary sclerosing cholangitis, asthma, type 1 diabetes, systemic lupus erythematosus, multiple sclerosis, autoimmune hyperthyroidism, psoriatic arthropathies, and polymyalgia rheumatica. The results of inverse variance weighting (IVW suggested that six diseases were associated with the development of prostate cancer. The three diseases that may increase the risk of prostate cancer are rheumatoid arthritis ( = 0.001), coxarthrosis ( < 0.001), and gonarthrosis ( = 0.008). The three possible protective factors against prostate cancer are primary sclerosing cholangitis ( = 0.001), autoimmune hyperthyroidism ( = 0.011), and psoriatic arthropathies ( = 0.001). Horizontal pleiotropy was not observed in the MR-Egger test.
Our findings provide predictive genetic evidence for an association between autoimmune disorders and prostate cancer. Further research is needed to explore the underlying mechanisms of comorbidities at the molecular level.
尽管许多流行病学研究和荟萃分析报告了自身免疫性疾病与前列腺癌之间存在关联，但尚无研究报告明确的相关性或关联方向。我们研究的目的是使用孟德尔随机化（MR）方法探索自身免疫相关疾病与前列腺癌之间的潜在关系。
我们在PubMed上检索了关键词为“自身免疫性疾病”和“前列腺癌”的文献，以寻找更多关于前列腺癌与自身免疫相关疾病相关性的线索。基于此文献检索，我们选择了16种有全基因组关联研究（GWAS）数据且可能与前列腺癌相关的自身免疫相关疾病。逆方差加权（IVW）方法被用作我们对两样本MR和多变量MR分析的主要分析方法，以估计比值比（OR）和95%置信区间（CI）。我们通过一系列敏感性分析进一步验证了我们结论的稳健性。
所选的自身免疫相关疾病包括类风湿性关节炎、强直性脊柱炎、髋关节炎、膝关节炎、克罗恩病、溃疡性结肠炎、肠易激综合征、乳糜泻、原发性硬化性胆管炎、哮喘、1型糖尿病、系统性红斑狼疮、多发性硬化症、自身免疫性甲状腺功能亢进、银屑病关节炎和风湿性多肌痛。逆方差加权（IVW）结果表明，六种疾病与前列腺癌的发生有关。可能增加前列腺癌风险的三种疾病是类风湿性关节炎（P = 0.001）、髋关节炎（P < 0.001）和膝关节炎（P = 0.008）。三种可能预防前列腺癌的因素是原发性硬化性胆管炎（P = 0.001）、自身免疫性甲状腺功能亢进（P = 0.011）和银屑病关节炎（P = 0.001）。在MR-Egger检验中未观察到水平多效性。
我们的研究结果为自身免疫性疾病与前列腺癌之间的关联提供了预测性遗传证据。需要进一步研究以探索共病在分子水平上的潜在机制。
