{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T17:15:20Z","timestamp":1779902120967,"version":"3.53.1"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T00:00:00Z","timestamp":1704412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Colorectal cancer and Alzheimer\u2019s disease are both common life-threatening diseases in the elderly population. Some studies suggest a possible inverse relationship between colorectal cancer and Alzheimer\u2019s disease, but real-world research is subject to many biases. We hope to clarify the causal relationship between the two through a bidirectional two-sample Mendelian randomization study.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> In our study, we used genetic summary data from large-scale genome-wide association studies to investigate the relationship between colorectal cancer and Alzheimer\u2019s disease. Our primary analysis employed the inverse-variance weighted method and we also used complementary techniques, including MR-Egger, weighted median estimator, and Maximum likelihood. We applied simex adjustment to the MR-Egger results. We also utilized the MRlap package to detect potential sample overlap and its impact on the bias of the results. In addition, we performed several sensitivity and heterogeneity analyses, to ensure the reliability of our results.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The combined effect size results of the inverse-variance weighted method indicate that colorectal cancer may decrease the incidence of Alzheimer\u2019s disease, with an odds ratio (OR) of 0.846 (95% CI: 0.762\u20130.929). Similar results were observed using other methods such as MR-Egger, weighted median estimator, and Maximum likelihood. On the other hand, Alzheimer\u2019s disease may slightly increase the incidence of colorectal cancer, with an OR of 1.014 (95% CI: 1.001\u20131.027). However, the results of one subgroup were not significant, and the results from MRlap indicated that sample overlap introduced bias into the results. Therefore, the results of the reverse validation are not reliable. The F-statistic for all SNPs was greater than 20. Four SNPs related to the outcome were excluded using Phenoscanner website but the adjustment did not affect the overall direction of the results. The results of these statistics were further validated by MR-PRESSO, funnel plots, leave-one-out analyses, Cochran\u2019s Q, demonstrating the reliability of the findings.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> According to the findings of this Mendelian randomization study, there appears to be a causal association between colorectal cancer and Alzheimer\u2019s disease. These results could have important implications for clinical practice in terms of how colorectal cancer and Alzheimer\u2019s disease are treated. To better understand the relationship between these two diseases, more research and screening are needed in clinical settings.<\/jats:p>","DOI":"10.3389\/fgene.2023.1180905","type":"journal-article","created":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T05:52:24Z","timestamp":1704433944000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Causal association between colorectal cancer and Alzheimer\u2019s disease: a bidirectional two-sample mendelian randomization study"],"prefix":"10.3389","volume":"14","author":[{"given":"Chunsheng","family":"Yuan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saisai","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kezhen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiyu","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yantong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jincheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e0133380","DOI":"10.1371\/journal.pone.0133380","article-title":"Perceived stress levels, chemotherapy, radiation treatment and tumor characteristics are associated with a persistent increased frequency of somatic chromosomal instability in women diagnosed with breast cancer: a one year longitudinal study","volume":"10","author":"Aboalela","year":"2015","journal-title":"PLoS One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"16199","DOI":"10.3390\/ijms232416199","article-title":"Relationship of cognition and Alzheimer's disease with gastrointestinal tract disorders: a large-scale genetic overlap and mendelian randomisation analysis","volume":"23","author":"Adewuyi","year":"2022","journal-title":"Int. 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