Qian Shuyi, Gong Yuting, Chen Ying
Department of Nephrology and Laboratory of Kidney Disease, Hunan Clinical Research Center for Chronic Kidney Disease, Hunan Provincial People's Hospital, Hunan Normal University, No. 61 Jiefang West Road, Furong District, Changsha, 410002, China.
Discov Oncol. 2025 Jun 1;16(1):974. doi: 10.1007/s12672-025-02785-9.
Observational studies have yielded inconsistent findings on the relationship between chronic kidney disease (CKD) and the risk of colorectal cancer (CRC). This research utilized a meta-analysis of cohort studies along with two-sample Mendelian randomization (MR) approaches to explore the causal impact of CKD on CRC.
A thorough search was performed across PubMed, Web of Science, Embase, and the Cochrane Library, encompassing all relevant studies from their inception until December 20, 2024. The data on the causal link between CKD and CRC were pooled using risk ratio (RR), with findings reported within 95% confidence interval (CI). For MR analysis, data were synthesized from genome-wide association studies (GWAS) that concentrated on CKD and CRC in cohorts of European descent. The inverse-variance weighted (IVW) approach was utilized as the primary method for MR analysis.
This meta-analysis encompassed 8 cohort studies involving 613,135 CKD patients and 733,068 controls. The pooled results revealed that CKD was associated with an increased risk of CRC in the total population (RR: 1.332, 95% CI 1.084-1.637, 95% prediction interval [PI] = 0.669-2.651). Subgroup analysis indicated that the association between CKD and elevated CRC risk was more pronounced in individuals younger than 50 years (RR: 2.119, 95% CI 1.205-3.725, 95% PI = 0.276-16.284) and in women (RR: 1.550, 95% CI 1.121-2.144, 95% PI = 0.594 to 4.043). Further MR analysis, using the IVW approach, showed a significant causal connection between CKD and the heightened CRC risk (odds ratio [OR]: 1.171, 95% CI 1.063-1.289, p = 0.001). Results from the sensitivity analyses provided no evidence of heterogeneity or horizontal pleiotropy in MR analysis.
Evidence from meta-analysis and MR analysis suggested that CKD may increase the risk of CRC. It remains essential to further investigate the relationship between CKD and CRC incidence across diverse ethnic populations.
观察性研究在慢性肾脏病（CKD）与结直肠癌（CRC）风险之间的关系上得出了不一致的结果。本研究采用队列研究的荟萃分析以及两样本孟德尔随机化（MR）方法，以探讨CKD对CRC的因果影响。
全面检索了PubMed、科学网、Embase和考克兰图书馆，涵盖从各库建库起至2024年12月20日的所有相关研究。使用风险比（RR）汇总CKD与CRC之间因果关系的数据，并在95%置信区间（CI）内报告结果。对于MR分析，数据来自专注于欧洲血统队列中CKD和CRC的全基因组关联研究（GWAS）。采用逆方差加权（IVW）方法作为MR分析的主要方法。
该荟萃分析纳入了8项队列研究，涉及613135例CKD患者和733068例对照。汇总结果显示，在总体人群中，CKD与CRC风险增加相关（RR：1.332，95%CI 1.084 - 1.637，95%预测区间[PI] = 0.669 - 2.651）。亚组分析表明，CKD与CRC风险升高之间的关联在50岁以下个体（RR：2.119，95%CI 1.205 - 3.725，95%PI = 0.276 - 16.284）和女性中（RR：1.550，95%CI 1.121 - 2.144，95%PI = 0.594至4.043）更为明显。使用IVW方法的进一步MR分析显示，CKD与CRC风险升高之间存在显著的因果关系（优势比[OR]：1.171，95%CI 1.063 - 1.289，p = 0.001）。敏感性分析结果未提供MR分析中存在异质性或水平多效性的证据。
荟萃分析和MR分析的证据表明，CKD可能增加CRC的风险。进一步研究不同种族人群中CKD与CRC发病率之间的关系仍然至关重要。
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