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ORIGINAL RESEARCH article

Front. Genet.
Sec. Nutritional Genomics
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1449205

Fatty acid traits mediate the effects of uric acid on cancers: A Mendelian randomization study

Provisionally accepted
Jianing Li Jianing Li 1Yongsheng Zhang Yongsheng Zhang 2Tong Fu Tong Fu 3Songyan Wang Songyan Wang 4Hongbo Cai Hongbo Cai 4Fenghua Xu Fenghua Xu 4Guoli Xing Guoli Xing 4Ying Tong Ying Tong 4*
  • 1 Heilongjiang University of Chinese Medicine, Harbin, China
  • 2 Harbin Institute of Technology, Harbin, Heilongjiang Province, China
  • 3 Brandeis University, Waltham, Massachusetts, United States
  • 4 First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China

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

    Introduction: Previous findings on the association between uric acid (UA) levels and cancer risk are conflicting. Moreover, the mechanisms underlying the interactions between UA levels, fatty acid traits, and cancer outcomes remain complex; it is still unclear whether elevated UA levels influence fatty acid traits and, thereby, contribute to an increased cancer risk. Therefore, we aimed to investigate the association between UA levels and cancer risk, with a specific focus on the potential mediating role of fatty acid traits. Methods: We employed a mendelian randomization (MR) analysis utilizing genetic data from large-scale genome-wide association studies to assess the causal relationships among UA levels, fatty acid traits, and cancer risk. The primary method used was the inverse variance-weighted approach alongside Bayesian-weighted mendelian randomization. Other MR models were also applied for comparison. Sensitivity analyses, based on various statistical assumptions, were also performed to evaluate the robustness of the findings. A two-step MR analysis was conducted to explore the mediating effects of fatty acid traits on the relationship between UA levels and cancer risk. Results and Discussion: Elevated UA levels were associated with an increased risk of in situ neoplasms, cervical cancer, and invasive mucinous ovarian cancer, while they were linked to a decreased risk of cancers of the eye and adnexa, small cell lung cancer, bronchus and lung cancer, respiratory system and intrathoracic organ cancers, as well as lung cancer. Mediation analysis revealed that fatty acid traits, particularly the docosahexaenoic acid/trans fatty acid ratio, mediated the relationship between UA levels and lung cancer risk. These findings underscore the potential of fatty acid traits to mediate the association between UA levels and cancer risk, offering new insights for targeted interventions and potentially improving clinical outcomes.

    Keywords: Mendelian randomization, Uric Acid, Fatty Acids, Cancer, Mediate

    Received: 27 Jun 2024; Accepted: 18 Nov 2024.

    Copyright: © 2024 Li, Zhang, Fu, Wang, Cai, Xu, Xing and Tong. 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: Ying Tong, First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.