Lipid Profiles, Telomere Length, and the Risk of Malignant Tumors: A Mendelian Randomization and Mediation Analysis

<b>Background/Objectives:</b> The relationship between lipid profiles, telomere length (TL), and cancer risk remains unclear. <b>Methods:</b> This study employed two-sample Mendelian randomization (MR) with mediation analysis to investigate their causal relationships, examini...

Full description

Saved in:
Bibliographic Details
Main Authors: Shupeng Liu, Zhengzheng Fu, Hui Liu, Yinghui Wang, Meijuan Zhou, Zhenhua Ding, Zhijun Feng
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/13/1/13
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832589047560667136
author Shupeng Liu
Zhengzheng Fu
Hui Liu
Yinghui Wang
Meijuan Zhou
Zhenhua Ding
Zhijun Feng
author_facet Shupeng Liu
Zhengzheng Fu
Hui Liu
Yinghui Wang
Meijuan Zhou
Zhenhua Ding
Zhijun Feng
author_sort Shupeng Liu
collection DOAJ
description <b>Background/Objectives:</b> The relationship between lipid profiles, telomere length (TL), and cancer risk remains unclear. <b>Methods:</b> This study employed two-sample Mendelian randomization (MR) with mediation analysis to investigate their causal relationships, examining lipid profiles as exposure, TL as mediator, and nine cancer types as outcomes. We conducted our analysis using two-stage least squares (2SLS) regression integrated with inverse variance weighted (IVW) methods to address potential endogeneity and strengthen our causal inference. <b>Results:</b> we found that unfavorable lipid profiles were causally linked to increased TL (<i>p</i> < 0.05). TL showed positive causal associations with lung and hematologic cancers (OR > 1, <i>p</i> < 0.05). Direct associations were observed between total and low-density lipoprotein (LDL) cholesterol and gastric cancer (OR < 1, <i>p</i> < 0.05), and between remnant cholesterol and colorectal cancer (OR > 1, <i>p</i> < 0.05). Mediation analysis revealed TL as a significant mediator in the pathway from lipid profiles to cancer development (<i>p</i> < 0.05). No horizontal pleiotropy was detected. <b>Conclusions:</b> Our findings suggest that lipid metabolism disorders may influence cancer development through telomere regulation, particularly in lung and hematologic cancers. This emphasizes the importance of lipid management in cancer prevention and treatment, especially for these cancer types.
format Article
id doaj-art-65c1734c9dbe43189bbfd5f6d13244c7
institution Kabale University
issn 2227-9059
language English
publishDate 2024-12-01
publisher MDPI AG
record_format Article
series Biomedicines
spelling doaj-art-65c1734c9dbe43189bbfd5f6d13244c72025-01-24T13:23:43ZengMDPI AGBiomedicines2227-90592024-12-011311310.3390/biomedicines13010013Lipid Profiles, Telomere Length, and the Risk of Malignant Tumors: A Mendelian Randomization and Mediation AnalysisShupeng Liu0Zhengzheng Fu1Hui Liu2Yinghui Wang3Meijuan Zhou4Zhenhua Ding5Zhijun Feng6Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Radiation Medicine, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of Tropical Disease Research, Department of Radiation Medicine, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of Tropical Disease Research, Department of Radiation Medicine, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of Tropical Disease Research, Department of Radiation Medicine, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of Tropical Disease Research, Department of Radiation Medicine, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of Tropical Disease Research, Department of Radiation Medicine, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of Tropical Disease Research, Department of Radiation Medicine, School of Public Health, Southern Medical University, Guangzhou 510515, China<b>Background/Objectives:</b> The relationship between lipid profiles, telomere length (TL), and cancer risk remains unclear. <b>Methods:</b> This study employed two-sample Mendelian randomization (MR) with mediation analysis to investigate their causal relationships, examining lipid profiles as exposure, TL as mediator, and nine cancer types as outcomes. We conducted our analysis using two-stage least squares (2SLS) regression integrated with inverse variance weighted (IVW) methods to address potential endogeneity and strengthen our causal inference. <b>Results:</b> we found that unfavorable lipid profiles were causally linked to increased TL (<i>p</i> < 0.05). TL showed positive causal associations with lung and hematologic cancers (OR > 1, <i>p</i> < 0.05). Direct associations were observed between total and low-density lipoprotein (LDL) cholesterol and gastric cancer (OR < 1, <i>p</i> < 0.05), and between remnant cholesterol and colorectal cancer (OR > 1, <i>p</i> < 0.05). Mediation analysis revealed TL as a significant mediator in the pathway from lipid profiles to cancer development (<i>p</i> < 0.05). No horizontal pleiotropy was detected. <b>Conclusions:</b> Our findings suggest that lipid metabolism disorders may influence cancer development through telomere regulation, particularly in lung and hematologic cancers. This emphasizes the importance of lipid management in cancer prevention and treatment, especially for these cancer types.https://www.mdpi.com/2227-9059/13/1/13lipid profilestelomere lengthdyslipidemiaMendelian randomizationmediation analysis
spellingShingle Shupeng Liu
Zhengzheng Fu
Hui Liu
Yinghui Wang
Meijuan Zhou
Zhenhua Ding
Zhijun Feng
Lipid Profiles, Telomere Length, and the Risk of Malignant Tumors: A Mendelian Randomization and Mediation Analysis
Biomedicines
lipid profiles
telomere length
dyslipidemia
Mendelian randomization
mediation analysis
title Lipid Profiles, Telomere Length, and the Risk of Malignant Tumors: A Mendelian Randomization and Mediation Analysis
title_full Lipid Profiles, Telomere Length, and the Risk of Malignant Tumors: A Mendelian Randomization and Mediation Analysis
title_fullStr Lipid Profiles, Telomere Length, and the Risk of Malignant Tumors: A Mendelian Randomization and Mediation Analysis
title_full_unstemmed Lipid Profiles, Telomere Length, and the Risk of Malignant Tumors: A Mendelian Randomization and Mediation Analysis
title_short Lipid Profiles, Telomere Length, and the Risk of Malignant Tumors: A Mendelian Randomization and Mediation Analysis
title_sort lipid profiles telomere length and the risk of malignant tumors a mendelian randomization and mediation analysis
topic lipid profiles
telomere length
dyslipidemia
Mendelian randomization
mediation analysis
url https://www.mdpi.com/2227-9059/13/1/13
work_keys_str_mv AT shupengliu lipidprofilestelomerelengthandtheriskofmalignanttumorsamendelianrandomizationandmediationanalysis
AT zhengzhengfu lipidprofilestelomerelengthandtheriskofmalignanttumorsamendelianrandomizationandmediationanalysis
AT huiliu lipidprofilestelomerelengthandtheriskofmalignanttumorsamendelianrandomizationandmediationanalysis
AT yinghuiwang lipidprofilestelomerelengthandtheriskofmalignanttumorsamendelianrandomizationandmediationanalysis
AT meijuanzhou lipidprofilestelomerelengthandtheriskofmalignanttumorsamendelianrandomizationandmediationanalysis
AT zhenhuading lipidprofilestelomerelengthandtheriskofmalignanttumorsamendelianrandomizationandmediationanalysis
AT zhijunfeng lipidprofilestelomerelengthandtheriskofmalignanttumorsamendelianrandomizationandmediationanalysis