School of Nursing, Zhejiang Chinese Medical University, Hangzhou, China.
First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.
Lipids Health Dis. 2024 Aug 20;23(1):256. doi: 10.1186/s12944-024-02241-7.
Recent studies have implicated remnant cholesterol (RC) in the etiology, progression, and prognosis of cancer. However, very few of them concentrated on the study of the precise relationship between serum RC levels and cancer risk, leaving this subject unexplored. Consequently, this study aims to investigate the association between serum RC levels and 4 site-specific cancers, employing a dual approach that combines observational and mendelian randomization (MR) analysis.
Based on data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2020, this study collected data from18,067 participants. To rule out confounders, this study utilized weighted multivariable logistic regression and assessed non-linear associations using restricted cubic spline (RCS) regression, followed by two-piecewise linear regression. Sensitivity analysis conducted in this study included subgroup analysis, multiple imputation, outlier removal, and propensity score matching. To strengthen causal inference, this study employed univariable and multivariable MR analysis. The robustness and reliability of the findings were estimated by the application of replication and meta-analysis.
The results of multivariable logistic regression analysis demonstrated a significant association between serum RC levels and breast cancer, showing that individuals in the higher logRC category had a higher risk of breast cancer compared to those in the lower category (Q3 vs. Q1: OR = 1.71, 95% CI: 1.01-2.88, P = 0.044). Weighted RCS revealed an inverted L-shape association between RC and the risk of breast cancer (P-nonlinear = 0.0386, P-overall = 0.010). Primary MR analysis provided evidence for an increased risk of breast (IVW: OR = 1.08, 95% CI: 1.03-1.12, P = 0.000951) and colorectal cancer (IVW: OR = 1.12, 95% CI: 1.00-1.24, P = 0.0476) associated with RC. However, the results of replication and meta-analysis did not support a significant causal association of RC with the risk of breast cancer (OR = 1.04, 95% CI: 0.95-1.13), lung cancer (OR = 0.95, 95% CI: 0.88-1.03), colorectal cancer (OR = 1.05, 95% CI: 0.92-1.19), and prostate cancer (OR = 1.01, 95% CI: 0.95-1.08).
Although a non-linear relationship was observed in the cross-sectional study between remnant cholesterol levels and breast cancer risk, MR analyses failed to provide any causal evidence.
最近的研究表明残胆固醇（RC）与癌症的病因、进展和预后有关。然而，很少有研究集中在研究血清 RC 水平与癌症风险之间的确切关系，因此这一主题仍未得到探索。因此，本研究旨在通过观察性和孟德尔随机化（MR）分析相结合的双重方法，研究血清 RC 水平与 4 个特定部位癌症之间的关系。
本研究基于 1999 年至 2020 年国家健康和营养检查调查（NHANES）的数据，从 18067 名参与者中收集数据。为了排除混杂因素，本研究采用加权多变量逻辑回归，并使用限制性立方样条（RCS）回归评估非线性关联，然后进行两段线性回归。本研究进行的敏感性分析包括亚组分析、多重插补、异常值剔除和倾向评分匹配。为了加强因果推断，本研究采用单变量和多变量 MR 分析。通过复制和荟萃分析来估计结果的稳健性和可靠性。
多变量逻辑回归分析的结果表明，血清 RC 水平与乳腺癌之间存在显著关联，与低类别相比，高 logRC 类别的个体患乳腺癌的风险更高（Q3 与 Q1：OR=1.71，95%CI：1.01-2.88，P=0.044）。加权 RCS 显示 RC 与乳腺癌风险之间呈倒 L 形关联（P-非线性=0.0386，P-总体=0.010）。主要的 MR 分析提供了证据表明，RC 与乳腺癌（IVW：OR=1.08，95%CI：1.03-1.12，P=0.000951）和结直肠癌（IVW：OR=1.12，95%CI：1.00-1.24，P=0.0476）风险增加有关。然而，复制和荟萃分析的结果并不支持 RC 与乳腺癌（OR=1.04，95%CI：0.95-1.13）、肺癌（OR=0.95，95%CI：0.88-1.03）、结直肠癌（OR=1.05，95%CI：0.92-1.19）和前列腺癌（OR=1.01，95%CI：0.95-1.08）风险之间存在因果关系的显著证据。
尽管横断面研究显示血清 RC 水平与乳腺癌风险之间存在非线性关系，但 MR 分析未能提供任何因果证据。
