精神分裂症与前列腺癌风险的关联：基于队列研究荟萃分析和孟德尔随机化分析的结果。
Association between schizophrenia and prostate cancer risk: Results from a pool of cohort studies and Mendelian randomization analysis.
机构信息
Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 511436, China; Guangdong Key Laboratory of Urology, Guangzhou Institute of Urology, Guangzhou 511436, China; Department of Clinical Medicine, First Clinical School, Guangzhou Medical University, Guangzhou 511436, China.
Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 511436, China; Guangdong Key Laboratory of Urology, Guangzhou Institute of Urology, Guangzhou 511436, China; Department of Clinical Medicine, Nanshan School, Guangzhou Medical University, Guangzhou 511436, China.
出版信息
Compr Psychiatry. 2022 May;115:152308. doi: 10.1016/j.comppsych.2022.152308. Epub 2022 Mar 12.
BACKGROUND
Observational studies analyzing the risk of prostate cancer in schizophrenia patients have generated mixed results. We performed a meta-analysis and a Mendelian randomization (MR) analysis to evaluate the relationship and causality between schizophrenia and the risk of prostate cancer.
METHODS
A comprehensive and systematic search of cohort studies was conducted, and a random-effects model meta-analysis was performed to calculate the standardized incidence ratios (SIRs) for prostate cancer incidence among schizophrenia patients versus the general population. To investigate the correlation between genetically-predicted schizophrenia and prostate cancer risk, we used summary statistics from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium (61,106 controls and 79,148 cases), and 75 schizophrenia-associated single nucleotide polymorphisms (SNP) from European descent as the instrumental variable.
RESULTS
In the meta-analysis of 13 cohort studies with 218,076 men involved, a decreased risk of prostate cancer was observed among schizophrenia patients [SIR 0.610; 95% confidence interval (CI) 0.500-0.740; p < 0.001] with significant heterogeneity (I = 83.3%; p < 0.001). However, MR analysis did not sustain the link between genetically-predicted schizophrenia and prostate cancer [odds ratio (OR) 1.033; 95% CI 0.998-1.069; p = 0.065]. The result was robust against extensive sensitivity analyses.
CONCLUSIONS
Our study indicated a decreased risk of prostate cancer in schizophrenia patients through meta-analysis, while MR analysis did not support the connection between schizophrenia and prostate cancer. Due to the interaction of genetic variants between binary exposures, we need to be cautious in interpreting and presenting causal associations. Moreover, further research is needed to investigate underlying factors that might link schizophrenia to the risk of prostate cancer.
背景
分析精神分裂症患者前列腺癌风险的观察性研究得出的结果不一。我们进行了荟萃分析和孟德尔随机分析（MR），以评估精神分裂症与前列腺癌风险之间的关系和因果关系。
方法
全面系统地检索了队列研究，并采用随机效应模型荟萃分析计算了精神分裂症患者与普通人群相比前列腺癌发病率的标准化发病比（SIR）。为了研究遗传预测的精神分裂症与前列腺癌风险之间的相关性，我们使用了前列腺癌协会（PCAG）的汇总统计数据来研究基因组相关的癌症改变（PRACTICAL）联盟（61106 名对照和 79148 例），以及 75 个来自欧洲血统的与精神分裂症相关的单核苷酸多态性（SNP）作为工具变量。
结果
在对 13 项涉及 218076 名男性的队列研究进行的荟萃分析中，精神分裂症患者前列腺癌的发病风险降低（SIR 0.610；95%置信区间 0.500-0.740；p<0.001），且存在显著的异质性（I=83.3%；p<0.001）。然而，MR 分析并未证实遗传预测的精神分裂症与前列腺癌之间存在关联（比值比 1.033；95%置信区间 0.998-1.069；p=0.065）。该结果在广泛的敏感性分析中仍然稳健。
结论
我们的研究通过荟萃分析表明精神分裂症患者前列腺癌的发病风险降低，而 MR 分析不支持精神分裂症与前列腺癌之间的关联。由于二元暴露之间遗传变异的相互作用，我们在解释和呈现因果关系时需要谨慎。此外，还需要进一步研究潜在的因素，这些因素可能将精神分裂症与前列腺癌的风险联系起来。
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