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. 2024 Aug 20;23(1):256.
doi: 10.1186/s12944-024-02241-7.

Association between remnant cholesterol and the risk of 4 site-specific cancers: evidence from a cross-sectional and Mendelian randomization study

Mengjie Li #  1 , Qi Liu #  2 , Ming Shi  1 , Manyi Fu  1 , Guijuan He  3
Affiliations

Association between remnant cholesterol and the risk of 4 site-specific cancers: evidence from a cross-sectional and Mendelian randomization study

Mengjie Li et al. Lipids Health Dis. .

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Keywords: Cancer; Mendelian randomization; NHANES; Remnant cholesterol.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Outline of the study design
Fig. 2
Fig. 2
RCS plot illustrating the association between RC and breast cancer. (A) Weighted RCS for Association of RC with breast cancer. (B) Unweighted RCS for Association of RC with breast cancer. (C) Weighted age RCS for Association of RC with breast cancer. (D) Unweighted age RCS for Association of RC with breast cancer
Fig. 3
Fig. 3
Meta-analysis of RC and 4 site-specific cancers. (A) RC and breast cancer. (B) RC and lung cancer. (C) RC and colorectal cancer. (D) RC and prostate cancer
See this image and copyright information in PMC

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