阿尔茨海默病（AD）和癌症是常见的与年龄相关的疾病，流行病学证据表明它们之间存在一种逆相关关系。然而，研究两者关系的潜在机制仍然不足。本研究利用GWAS目录中的42,034名AD患者和609,951名癌症患者的全基因组关联概览统计数据，采用双样本遗传学随机化（MR）方法。此外，我们采用两步MR方法确定介导AD和癌症之间关系的代谢产物。此外，我们采用共定位分析，通过对33种TCGA癌症类型的转录组数据进行分析，确定上调与AD风险相关基因，并证明这些基因的上调对癌症有益的预后因素。双样本MR分析揭示增加AD风险对降低癌症风险具有显著的因果影响。两步MR分析确认了极低密度脂蛋白（VLDL）作为AD和癌症之间负相关因果关系的关键介质。共定位分析揭示了PVRIG上调是AD风险的一个因素。转录组分析显示，在全癌症和多种癌症类型中，PVRIG表达与干细胞程度评分显著负相关，并与抗肿瘤免疫反应和整体生存率呈正相关。AD可能导致较低的癌症风险。VLDL是AD与癌症之间的一个重要中间变量。PVRIG的丰度对AD是一个风险因素，但对癌症是一个保护因素。本研究证明了AD对癌症的因果关系，并提供了两种疾病之间潜在的分子联系。© 2023年 BioMed Central Ltd., Springer Nature的一部分。

Alzheimer's disease (AD) and cancer are common age-related diseases, and epidemiological evidence suggests an inverse relationship between them. However, investigating the potential mechanism underlying their relationship remains insufficient.Based on genome-wide association summary statistics for 42,034 AD patients and 609,951 cancer patients from the GWAS Catalog using the two-sample Mendelian randomization (MR) method. Moreover, we utilized two-step MR to identify metabolites mediating between AD and cancer. Furthermore, we employed colocalization analysis to identify genes whose upregulation is a risk factor for AD and demonstrated the genes' upregulation to be a favorable prognostic factor for cancer by analyzing transcriptomic data for 33 TCGA cancer types.Two-sample MR analysis revealed a significant causal influence for increased AD risk on reduced cancer risk. Two-step MR analysis identified very low-density lipoprotein (VLDL) as a key mediator of the negative cause-effect relationship between AD and cancer. Colocalization analysis uncovered PVRIG upregulation to be a risk factor for AD. Transcriptomic analysis showed that PVRIG expression had significant negative correlations with stemness scores, and positive correlations with antitumor immune responses and overall survival in pan-cancer and multiple cancer types.AD may result in lower cancer risk. VLDL is a significant intermediate variable linking AD with cancer. PVRIG abundance is a risk factor for AD but a protective factor for cancer. This study demonstrates a causal influence for AD on cancer and provides potential molecular connections between both diseases.© 2023. BioMed Central Ltd., part of Springer Nature.