阿尔茨海默病（AD）在女性中发病率较高。先前的流行病学研究表明 AD 与妇科癌症之间存在潜在关联，但它们之间的因果关系仍不清楚。本研究旨在采用双向孟德尔随机化 (MR) 方法探讨 12 种妇科癌症与 AD 之间的因果关系。我们利用最广泛的全基因组关联研究的数据获得了 AD 的遗传相关工具。 12 种妇科癌症的遗传相关数据也来自芬兰生物库。这些癌症包括乳腺癌（BC）、宫颈腺癌（CA）、宫颈鳞状细胞癌（CSCC）、宫颈癌（CC）、子宫内膜癌（EC）、卵巢子宫内膜样癌（OEC）、卵巢癌（OC）、卵巢浆液性癌癌（OSC）、乳腺癌原位癌（BCIS）、宫颈原位癌（CCIS）、子宫内膜原位癌（ECIS）和外阴原位癌（VCIS）。我们使用逆方差加权（IVW）模型进行因果分析，并进行水平多效性检验、异质性检验、MR-PRESSO检验和留一分析，以确保结果的稳健性。我们还应用复制分析和荟萃分析来进一步验证我们的实验结果。研究发现EC (P_IVW =0.037, OR [95% CI] = 1.032 [1.002, 1.064])和CCIS (P_IVW = 0.046, OR [95] % CI] = 1.032 [1.011, 1.064]）增加 AD 风险，而 OC 与 AD 呈负相关（P_IVW = 0.016，OR [95% CI] = 0.974[0.954, 0.995]）。在反向 MR 分析中，AD 增加 CC（P_IVW = 0.039，OR [95% CI] = 1.395 [1.017, 1.914]）和 VCIS（P_IVW = 0.041，OR [95% CI] = 1.761 [1.027, 2.021]）的风险），但与 OEC 呈负相关（P_IVW = 0.034，OR [95% CI] = 0.634 [0.417, 0.966]）。敏感性分析结果证明了稳健性。这些发现通过重复和荟萃分析得到了进一步证实。我们的 MR 研究支持 AD 和妇科癌症之间的因果关系。这鼓励进一步研究女性阿尔茨海默氏症患者妇科癌症的发病率以及积极预防 AD。© 2024。作者。

Alzheimer's disease (AD) manifests with a higher rate of occurrence in women. Previous epidemiological studies have suggested a potential association between AD and gynecological cancers, but the causal relationship between them remains unclear. This study aims to explore the causal link between 12 types of gynecological cancers and AD using a bidirectional Mendelian randomization (MR) approach.We obtained genetic correlation tools for AD using data from the most extensive genome-wide association study. Genetic correlation data for 12 types of gynecological cancers were also sourced from the Finnish Biobank. These cancers include breast cancer (BC), cervical adenocarcinoma (CA), cervical squamous cell carcinoma (CSCC), cervical cancer (CC), endometrial cancer (EC), ovarian endometrioid carcinoma (OEC), ovarian cancer (OC), ovarian serous carcinoma (OSC), breast carcinoma in situ (BCIS), cervical carcinoma in situ (CCIS), endometrial carcinoma in situ (ECIS), and vulvar carcinoma in situ (VCIS). We used the inverse-variance weighted (IVW) model for causal analysis and conducted horizontal pleiotropy tests, heterogeneity tests, MR-PRESSO tests, and leave-one-out analyses to ensure the robustness of our results. We also applied replication analysis and meta-analysis to further validate our experimental results.The study found that EC (P_IVW =0.037, OR [95% CI] = 1.032 [1.002, 1.064]) and CCIS (P_IVW = 0.046, OR [95% CI] = 1.032 [1.011, 1.064]) increase the risk of AD, whereas OC was negatively correlated with AD (P_IVW = 0.016, OR [95% CI] = 0.974[0.954, 0.995]). In reverse MR analysis, AD increased the risk of CC (P_IVW = 0.039, OR [95% CI] = 1.395 [1.017, 1.914]) and VCIS (P_IVW = 0.041, OR [95% CI] = 1.761 [1.027, 2.021]), but was negatively correlated with OEC (P_IVW = 0.034, OR [95% CI] = 0.634 [0.417, 0.966]). Sensitivity analysis results demonstrated robustness. These findings were further substantiated through replication and meta-analyses.Our MR study supports a causal relationship between AD and gynecological cancers. This encourages further research into the incidence of gynecological cancers in female Alzheimer's patients and the active prevention of AD.© 2024. The Author(s).