Vahed Iman Elahi, Esmaili Zahra, Mamaghani Mina Pourhabib, Farshid Shohreh, Salarian Behina, Alamdari Mobina, Azimizadeh Zahra, Rastad Zahra, Radmard Hoda, Soltaninejad Hossein, Rahmanian Mohammad
School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Shiraz University of Medical Sciences, Shiraz, Iran.
PLoS One. 2025 Oct 16;20(10):e0333907. doi: 10.1371/journal.pone.0333907. eCollection 2025.
Colorectal cancer (CRC) ranks as the third most prevalent cancer globally and the second leading cause of cancer-related mortality. Based on recent studies, lipid levels may have a relationship with the risk of CRC. This meta-analysis aims to better understand the association between various serum lipids and CRC risk.
A comprehensive search was conducted in Web of Science, PubMed, and Scopus. This meta-analysis, including only prospective cohort studies, performed random-effects meta-analyses using the Restricted Maximum Likelihood (REML) model to assess the association between the highest versus lowest categories of serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoproteins (LDL) with the risk of CRC, primarily using hazard ratios (HR) as the effect size. Subgroup analyses (e.g., by tumor site, region, and risk of bias) and meta-regression analyses (e.g., for mean age, mean BMI, sex distribution, and duration of follow-up) were conducted to explore heterogeneity. Dose-response analyses were performed utilizing three model types.
Following the screening of 27,278 articles, 23 articles have been included in this study finally. The associations between TG, TC, HDL, and LDL levels and the risk of CRC, colon, and rectum cancers were examined separately. Higher levels of TC were not significantly associated with the risk of CRC (HR = 1.08; 95% CI: 0.90-1.30; I2 = 50.55%; p = 0.4187) and colon cancer (HR = 1.08; 95% CI: 0.99-1.18; I2 = 35.57%; p = 0.0720), but were significantly associated with an increased risk of rectum cancer (HR = 1.19; 95% CI: 1.08-1.32; I2 = 28.36%; p = 0.0004). Higher levels of TG were associated with an increased hazard of CRC (HR 1.11; 95% CI: 1.044-1.18; I2 = 0.0%; p = 0.0008). For colon cancer, TG showed a marginally significant association (HR 1.23; 95% CI: 0.99-1.55; I2 = 52.0%; p = 0.0576). No significant association was found between TG levels and rectum cancer risk (HR 1.036; 95% CI: 0.69-1.56; I2 = 67.29%; p = 0.8674).Also, higher levels of HDL were not significantly associated with the risk of CRC (HR 0.93; 95% CI: 0.83-1.03; I2 = 28.8%; p = 0.1527), colon cancer (HR 0.94; 95% CI: 0.75-1.19; I2 = 0.0%; p = 0.6243), and rectum cancer (HR: 0.95; 95% CI: 0.66;1.37; I2 = 0.0%; p = 0.7888). For colon cancer, higher LDL level was not significantly associated with risk (HR 0.91; 95% CI: 0.60-1.37; p = 0.21; I2 = 37%; p = 6558). Accordingly quadratic and RCS models represented as lowest AIC for TC (p = 0.026), for TG (p = 0.004), for LDL (p = 0.942) and for HDL (p = 0.295).
Higher TG level was significantly associated with increased risk of CRC and showed a borderline association with colon cancer (HR 1.23, 95% CI 0.99-1.55; p = 0.0576), while TC, HDL, and LDL showed no significant associations with these cancers. For rectum cancer, higher TC was significantly linked to increased risk, whereas TG, HDL, and LDL showed no significant associations. Future research should prioritize longitudinal studies to investigate the mechanistic roles of hormones and the gut microbiota in modulating colorectal cancer risk, alongside multi-omics studies that integrate lipid metabolism with other biological variables such as inflammatory markers and genetic predispositions. These efforts could clarify causal pathways and inform targeted prevention strategies.
结直肠癌（CRC）是全球第三大常见癌症，也是癌症相关死亡的第二大主要原因。根据最近的研究，血脂水平可能与结直肠癌风险有关。本荟萃分析旨在更好地了解各种血清脂质与结直肠癌风险之间的关联。
在Web of Science、PubMed和Scopus中进行了全面检索。本荟萃分析仅纳入前瞻性队列研究，使用限制最大似然（REML）模型进行随机效应荟萃分析，以评估血清甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白（HDL）和低密度脂蛋白（LDL）最高类别与最低类别与结直肠癌风险之间的关联，主要使用风险比（HR）作为效应量。进行了亚组分析（如按肿瘤部位、地区和偏倚风险）和荟萃回归分析（如针对平均年龄、平均BMI、性别分布和随访持续时间）以探索异质性。利用三种模型类型进行剂量反应分析。
在筛选的27278篇文章中，最终有23篇文章纳入本研究。分别检查了TG、TC、HDL和LDL水平与结直肠癌、结肠癌和直肠癌风险之间的关联。较高的TC水平与结直肠癌风险（HR = 1.08；95% CI：0.90 - 1.30；I2 = 50.55%；p = 0.4187）和结肠癌风险（HR = 1.08；95% CI：0.99 - 1.18；I2 = 35.57%；p = 0.0720）无显著关联，但与直肠癌风险增加显著相关（HR = 1.19；95% CI：1.08 - 1.32；I2 = 28.36%；p = 0.0004）。较高的TG水平与结直肠癌风险增加相关（HR 1.11；95% CI：1.044 - 1.18；I2 = 0.0%；p = 0.0008）。对于结肠癌，TG显示出边缘显著关联（HR 1.23；95% CI：0.99 - 1.55；I2 = 52.0%；p = 0.0576）。未发现TG水平与直肠癌风险之间存在显著关联（HR 1.036；95% CI：0.69 - 1.56；I2 = 67.29%；p = 0.8674）。此外，较高的HDL水平与结直肠癌风险（HR 0.93；95% CI：0.83 - 1.03；I2 = 28.8%；p = 0.1527）、结肠癌风险（HR 0.94；95% CI：0.75 - 1.19；I2 = 0.0%；p = 0.6243）和直肠癌风险（HR：0.95；95% CI：0.66；1.37；I2 = 0.0%；p = 0.7888）均无显著关联。对于结肠癌，较高的LDL水平与风险无显著关联（HR 0.91；95% CI：0.60 - 1.37；p = 0.21；I2 = 37%；p = 6558）。因此，二次模型和RCS模型在TC（p = 0.026）、TG（p = 0.004）、LDL（p = 0.942）和HDL（p = 0.295）方面表现出最低的AIC。
较高的TG水平与结直肠癌风险增加显著相关，与结肠癌存在边缘关联（HR 1.23，95% CI 0.99 - 1.55；p = 0.0576），而TC、HDL和LDL与这些癌症无显著关联。对于直肠癌，较高的TC与风险增加显著相关，而TG、HDL和LDL无显著关联。未来的研究应优先进行纵向研究，以调查激素和肠道微生物群在调节结直肠癌风险中的机制作用，同时进行多组学研究，将脂质代谢与其他生物变量如炎症标志物和遗传易感性整合起来。这些努力可以阐明因果途径并为有针对性的预防策略提供信息。
