Causal Effects of Circulating Lipid Traits on Epithelial Ovarian Cancer: A Two-Sample Mendelian Randomization Study

Ovarian cancer (OC), and particularly epithelial OC (EOC), is an increasing challenge for women. Circulating lipids play different roles in the occurrence and development of OC, but no causal relationship has been confirmed. We used two-sample Mendelian randomization (MR) to evaluate the genetic eff...

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Main Authors: Hongen Meng, Rong Wang, Zijun Song, Fudi Wang
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Metabolites
Subjects:
Online Access:https://www.mdpi.com/2218-1989/12/12/1175
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author Hongen Meng
Rong Wang
Zijun Song
Fudi Wang
author_facet Hongen Meng
Rong Wang
Zijun Song
Fudi Wang
author_sort Hongen Meng
collection DOAJ
description Ovarian cancer (OC), and particularly epithelial OC (EOC), is an increasing challenge for women. Circulating lipids play different roles in the occurrence and development of OC, but no causal relationship has been confirmed. We used two-sample Mendelian randomization (MR) to evaluate the genetic effects of circulating Apolipoprotein A1 (APOA1), Apolipoprotein B (APOB), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyc-erides (TG) on EOC risks based on summary data obtained from the UK Biobank and the Ovarian Cancer Association Consortium. We used the inverse-variance weight as the main statistical method and the MR-Egger, weighted median, and MR-PRESSO for sensitivity analysis. A 1-SD increment in HDL gave odds ratios (OR) and 95% confidence intervals (CI) of OR = 0.80 (95% CI: 0.69–0.93), OR = 0.77 (95% CI: 0.66–0.90), and OR = 0.76 (95% CI: 0.63–0.90) for low malignant potential OC (LMPOC), low-grade low malignant OC (LGLMSOC), and low malignant serous OC (LMSOC), respectively. Genetic liability due to TG was associated with an increased risk of LGLMSOC and LGSOC and a suggestive association with an increased risk of LMSOC (<i>p</i> = 0.001, <i>p</i> = 0.007, and <i>p</i> = 0.027, respectively). Circulating HDL was negatively associated with the risk of LMPOC, LGLMSOC, and LMSOC, while elevated circulating TG levels genetically predicted an increased risk of LGLMSOC and LGSOC. Further research is needed to investigate the causal effects of lipids on EOC and potential intervention and therapeutic targets.
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spelling doaj.art-80ce32a81d0f45e9b677c7b40bb1226a2023-11-24T16:36:59ZengMDPI AGMetabolites2218-19892022-11-011212117510.3390/metabo12121175Causal Effects of Circulating Lipid Traits on Epithelial Ovarian Cancer: A Two-Sample Mendelian Randomization StudyHongen Meng0Rong Wang1Zijun Song2Fudi Wang3The Fourth Affiliated Hospital, The First Affiliated Hospital, Institute of Translational Medicine, School of Public Health, Cancer Center, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou 310030, ChinaThe Fourth Affiliated Hospital, The First Affiliated Hospital, Institute of Translational Medicine, School of Public Health, Cancer Center, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou 310030, ChinaThe Fourth Affiliated Hospital, The First Affiliated Hospital, Institute of Translational Medicine, School of Public Health, Cancer Center, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou 310030, ChinaThe Fourth Affiliated Hospital, The First Affiliated Hospital, Institute of Translational Medicine, School of Public Health, Cancer Center, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou 310030, ChinaOvarian cancer (OC), and particularly epithelial OC (EOC), is an increasing challenge for women. Circulating lipids play different roles in the occurrence and development of OC, but no causal relationship has been confirmed. We used two-sample Mendelian randomization (MR) to evaluate the genetic effects of circulating Apolipoprotein A1 (APOA1), Apolipoprotein B (APOB), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyc-erides (TG) on EOC risks based on summary data obtained from the UK Biobank and the Ovarian Cancer Association Consortium. We used the inverse-variance weight as the main statistical method and the MR-Egger, weighted median, and MR-PRESSO for sensitivity analysis. A 1-SD increment in HDL gave odds ratios (OR) and 95% confidence intervals (CI) of OR = 0.80 (95% CI: 0.69–0.93), OR = 0.77 (95% CI: 0.66–0.90), and OR = 0.76 (95% CI: 0.63–0.90) for low malignant potential OC (LMPOC), low-grade low malignant OC (LGLMSOC), and low malignant serous OC (LMSOC), respectively. Genetic liability due to TG was associated with an increased risk of LGLMSOC and LGSOC and a suggestive association with an increased risk of LMSOC (<i>p</i> = 0.001, <i>p</i> = 0.007, and <i>p</i> = 0.027, respectively). Circulating HDL was negatively associated with the risk of LMPOC, LGLMSOC, and LMSOC, while elevated circulating TG levels genetically predicted an increased risk of LGLMSOC and LGSOC. Further research is needed to investigate the causal effects of lipids on EOC and potential intervention and therapeutic targets.https://www.mdpi.com/2218-1989/12/12/1175circulating lipidapolipoproteintriglycerideMendelian randomizationepithelial ovarian cancer
spellingShingle Hongen Meng
Rong Wang
Zijun Song
Fudi Wang
Causal Effects of Circulating Lipid Traits on Epithelial Ovarian Cancer: A Two-Sample Mendelian Randomization Study
Metabolites
circulating lipid
apolipoprotein
triglyceride
Mendelian randomization
epithelial ovarian cancer
title Causal Effects of Circulating Lipid Traits on Epithelial Ovarian Cancer: A Two-Sample Mendelian Randomization Study
title_full Causal Effects of Circulating Lipid Traits on Epithelial Ovarian Cancer: A Two-Sample Mendelian Randomization Study
title_fullStr Causal Effects of Circulating Lipid Traits on Epithelial Ovarian Cancer: A Two-Sample Mendelian Randomization Study
title_full_unstemmed Causal Effects of Circulating Lipid Traits on Epithelial Ovarian Cancer: A Two-Sample Mendelian Randomization Study
title_short Causal Effects of Circulating Lipid Traits on Epithelial Ovarian Cancer: A Two-Sample Mendelian Randomization Study
title_sort causal effects of circulating lipid traits on epithelial ovarian cancer a two sample mendelian randomization study
topic circulating lipid
apolipoprotein
triglyceride
Mendelian randomization
epithelial ovarian cancer
url https://www.mdpi.com/2218-1989/12/12/1175
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