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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Reproduction
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1446457
This article is part of the Research Topic Adipose tissue and adipokines: their roles in human reproduction View all 4 articles

Genetic association of lipids and lipid-lowering drug target genes with Endometrial carcinoma: A drug target Mendelian randomization study

Provisionally accepted
Zhehan Yang Zhehan Yang 1Junpan Chen Junpan Chen 1Minghao Wen Minghao Wen 1Jiayuan Lei Jiayuan Lei 2Ming Zeng Ming Zeng 1Sichen Li Sichen Li 1Yao Long Yao Long 1Zhiyi Zhou Zhiyi Zhou 1*Chunyan Wang Chunyan Wang 1*
  • 1 Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
  • 2 The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, Guangdong, China

The final, formatted version of the article will be published soon.

    Background: Aberrant lipid metabolism is intricately linked to the development of endometrial cancer, and statin lipid-lowering medications are regarded as promising adjunctive therapies for future management of this malignancy. This study employed Mendelian randomization (MR) to explore the causal association between lipid traits and endometrial cancer while assessing the potential impact of drug targets on lower lipids on endometrial cancer.Method: Two-sample Mendelian randomization was employed to probe the causal association between lipid traits and endometrial carcinoma. Drug-target Mendelian randomization was also utilized to identify potential drug-target genes for managing endometrial carcinoma. In instances where lipid-mediated effects through particular drug targets were notable, the impacts of these drug targets on endometrial carcinoma risk factors were investigated to bolster the findings.: No causal association between genetically predicted lipid traits (LDL-C, TG, TC, and HDL-C) and EC was found in two-sample Mendelian randomization. In drug target Mendelian randomization, genetic modeling of apolipoprotein B (APOB) (OR [95%CI]=0.31, [0.16-0.60]; p=4.73e-04) and cholesteryl ester transfer protein (CETP) (OR [95%CI]=1.83, [1.38-2.43]; p=2.91e-05) genetic mimicry was associated with non-endometrioid carcinoma.The results of our MR study revealed no causal association between genetically predicted lipid traits (LDL-C, TG, TC, and HDL-C) and EC. Among the six lipid-lowering drug targets, we observed a significant association between lower predicted APOB levels and higher CETP levels with an increased risk of endometrioid carcinoma. These findings provide novel insights into the importance of lipid regulation in individuals with endometrial carcinoma, warranting further clinical validation and mechanistic investigations.

    Keywords: Endometrioid carcinoma, Mendelian randomization, ApoB, CETP, drug target

    Received: 09 Jun 2024; Accepted: 25 Jul 2024.

    Copyright: © 2024 Yang, Chen, Wen, Lei, Zeng, Li, Long, Zhou and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Zhiyi Zhou, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
    Chunyan Wang, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

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