Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Front Endocrinol (Lausanne). 2024 Jun 6;15:1322253. doi: 10.3389/fendo.2024.1322253. eCollection 2024.
Evidence has been increasingly pointing towards a potential link between phenotypes related to obesity and the incidence of colorectal cancer. However, confirming this as a direct causal connection remains elusive. This investigation aims to elucidate the causative links between obesity-associated phenotypes and the incidence of colorectal cancer.
Employing the Two Sample Mendelian Randomization (TwoSampleMR) R package, analyses were conducted using Mendelian randomization (MR) to discern potential causative links between obesity categories sourced from both the Institute for Education and University (IEU) Open GWAS Project and Zenodo, and colorectal tumors (data obtained from IEU Open GWAS and FinnGen). For primary evaluations, the study utilized the Wald ratio and the Inverse Variance Weighting (IVW) methods, while the MR-Egger approach was integrated for sensitivity assessment. Bidirectional Mendelian Randomization (Bidirectional MR), as well as Linkage Disequilibrium (LD) Score Regression with well-imputed HapMap3 single nucleotide polymorphisms (SNPs), were additionally executed. Sensitivity assessments entailed IVW, MR-Egger methodologies to assess heterogeneity and pleiotropy, along with a leave-one-out strategy. Instrumental variables were chosen judiciously based on predetermined P-value thresholds and F-statistics.
Results from MR evaluations did not identify a clear causative link between BMI and colorectal malignancy. Conversely, both measures of obesity, the Waist-Hip Ratio (WHR) and its adjusted form for BMI (WHRadjBMI), displayed a connection to increased risk of colorectal cancer, especially prominent among female subjects. Reverse MR analyses dismissed potential reverse causality between colorectal malignancies and obesity. A significant genetic interplay was observed between WHR, WHRadjBMI, and colorectal cancer instances. Ensuing MR probes spotlighted inflammatory bowel ailment as a protective factor, while salad intake was indicated as a potential risk concerning colorectal malignancies. Sensitivity reviews, which included tests for both pleiotropy and heterogeneity, validated the robustness of the MR findings.
Findings from this research indicate that specific obesity-related parameters, notably WHR and WHRadjBMI, carry a causal relationship with an elevated colorectal cancer risk. The impact is distinctly more evident among females. Such insights might be pivotal for public health deliberations, hinting that individuals boasting a high WHR might necessitate intensified colorectal cancer screenings.
越来越多的证据表明，肥胖相关表型与结直肠癌的发病率之间可能存在关联。然而，证实这是一种直接的因果关系仍然难以捉摸。本研究旨在阐明与肥胖相关表型和结直肠癌发病率之间的因果关系。
使用 Two Sample Mendelian Randomization (TwoSampleMR) R 包，采用 Mendelian randomization (MR) 分析方法，使用来自 Institute for Education and University (IEU) Open GWAS Project 和 Zenodo 的肥胖类别和结直肠肿瘤（数据来自 IEU Open GWAS 和 FinnGen）进行分析。对于主要评估，研究使用 Wald 比值和Inverse Variance Weighting (IVW) 方法，同时使用 MR-Egger 方法进行敏感性评估。此外，还进行了双向 Mendelian Randomization (Bidirectional MR) 和基于 well-imputed HapMap3 单核苷酸多态性 (SNP) 的 Linkage Disequilibrium (LD) Score Regression 敏感性评估。使用 IVW、MR-Egger 方法评估异质性和多效性，以及采用逐个删除策略。根据预设的 P 值阈值和 F 统计量，明智地选择了工具变量。
MR 评估结果表明，BMI 与结直肠恶性肿瘤之间没有明确的因果关系。相反，肥胖的两种衡量标准，腰围-臀围比（WHR）及其调整后的 BMI 形式（WHRadjBMI），与结直肠癌风险增加相关，尤其是在女性中更为明显。反向 MR 分析排除了结直肠癌和肥胖之间潜在的反向因果关系。在 WHR、WHRadjBMI 和结直肠癌病例之间观察到显著的遗传相互作用。随后的 MR 探测强调了炎症性肠病作为保护因素，而沙拉摄入则被认为是结直肠癌的潜在风险因素。包括多效性和异质性测试在内的敏感性审查验证了 MR 研究结果的稳健性。
本研究结果表明，特定的肥胖相关参数，特别是 WHR 和 WHRadjBMI，与结直肠癌风险升高有因果关系。这种影响在女性中更为明显。这些发现对于公共卫生讨论可能至关重要，表明 WHR 较高的个体可能需要加强结直肠癌筛查。
