Li Wenjie, Huang Mingkai, Wang Rong, Wang Wei
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Cardiovasc Med. 2023 Jan 5;9:974402. doi: 10.3389/fcvm.2022.974402. eCollection 2022.
Increasing incidences of both atrial fibrillation (AF) and cancer have been observed in recent years. However, the casual association of both serious conditions has been scarcely evaluated and is considered to be a blank slate in cardio-oncology. Thus, we introduced Mendelian randomization (MR) methods to estimate the effects of AF on cancer risks.
We performed univariable and multivariable two-sample MR analyses to evaluate the effects of AF on the risk of 19 site-specific types of cancer. This MR study was conducted based on 111 independent AF-associated genetic instruments from genome-wide association studies and summarized-level data from corresponding cancer consortia. Multiple sensitivity analyses, including the leave-one-out analysis, MR-Egger regression, and MR-PRESSO tests, were further performed to examine the potential directional pleiotropic effects. Functional annotation was performed for common differentially expressed genes of AF and prostate cancer (PCA).
A total of 6,777,155 European-descent people, including 533,725 cases and 6,243,430 controls, were included in the present MR analysis. Univariable MR analyses demonstrated a causal effect of AF on the incidence of PCA [odds ratio (OR): 0.96; 95% confidence interval (CI) 0.92-0.99, = 0.01], and the causal effect remained significant (OR: 0.65; 95% CI 0.47-0.90, = 0.01) after adjusting for potential confounders through the multivariable MR approach. However, no casual associations between AF and the other 18 site-specific cancer risks were observed (all -values were > 0.05). The consistency of outcomes across complementary sensitivity MR methods further supported the causality. The functional analysis emphasized the essential role of antioxidant and xenobiotic catabolic processes in AF and PCA.
Contrary to the findings of several previous observational studies, our comprehensive MR analyses did not corroborate a causal role for AF in increasing the risk of various types of cancer. They did, however, demonstrate that AF may decrease the risk of PCA. Studies from larger sample sizes and individuals with different ethnic backgrounds are required to further support our conclusions.
近年来，房颤（AF）和癌症的发病率均呈上升趋势。然而，这两种严重疾病之间的因果关系鲜有评估，在心脏肿瘤学领域被认为是一片空白。因此，我们引入孟德尔随机化（MR）方法来估计房颤对癌症风险的影响。
我们进行了单变量和多变量双样本MR分析，以评估房颤对19种特定部位癌症风险的影响。这项MR研究基于全基因组关联研究中的111个独立的房颤相关基因工具以及相应癌症联盟的汇总数据进行。进一步进行了多种敏感性分析，包括留一法分析、MR-Egger回归和MR-PRESSO检验，以检验潜在的方向性多效性效应。对房颤和前列腺癌（PCA）的常见差异表达基因进行了功能注释。
本MR分析共纳入了6,777,155名欧洲血统人群，包括533,725例病例和6,243,430名对照。单变量MR分析显示房颤对PCA发病率有因果效应[比值比（OR）：0.96；95%置信区间（CI）0.92 - 0.99，P = 0.01]，通过多变量MR方法调整潜在混杂因素后，因果效应仍然显著（OR：0.65；95% CI 0.47 - 0.90，P = 0.01）。然而，未观察到房颤与其他18种特定部位癌症风险之间存在因果关联（所有P值均> 0.05）。互补敏感性MR方法结果的一致性进一步支持了因果关系。功能分析强调了抗氧化和外源性物质分解代谢过程在房颤和PCA中的重要作用。
与之前几项观察性研究的结果相反，我们全面的MR分析并未证实房颤在增加各类癌症风险中起因果作用。然而，研究确实表明房颤可能降低PCA的风险。需要来自更大样本量和不同种族背景个体的研究来进一步支持我们的结论。
