Genetic prediction of causal association between serum bilirubin and hematologic malignancies: a two-sample Mendelian randomized and bioinformatics study

Lihua Lu; Luting Luo; Xiang Li; Wanying Liu; Boheng Wu; Qing Cai; Jiazheng Li; Yan Huang; Yanxin Chen; Yongzhi Zheng; Jianda Hu

doi:10.3389/fonc.2024.1364834

Genetic prediction of causal association between serum bilirubin and hematologic malignancies: a two-sample Mendelian randomized and bioinformatics study

Front Oncol. 2024 Apr 8:14:1364834. doi: 10.3389/fonc.2024.1364834. eCollection 2024.

Authors

Lihua Lu^#¹, Luting Luo^#², Xiang Li^#², Wanying Liu², Boheng Wu¹, Qing Cai², Jiazheng Li², Yan Huang¹, Yanxin Chen¹, Yongzhi Zheng¹, Jianda Hu^{1

2

3}

Affiliations

¹ Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
² The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China.
³ Institute of Precision Medicine, Fujian Medical University, Fuzhou, Fujian, China.

^# Contributed equally.

Abstract

Introduction: An increasing number of cohort studies have shown a correlation between serum bilirubin and tumors, but no definitive causal relationship has been established between serum bilirubin and hematological malignancies.Therefore, the aim of the present study was to assess the causal relationship of serum bilirubin, including total bilirubin (TBIL) and direct bilirubin (DBIL), with hematological malignancies, including leukemia, lymphoma, and myeloma.

Methods: We used a genome-wide association study (GWAS) collection of TBIL, DBIL, and hematological malignancies data. Using two-sample Mendelian randomization(MR), we assessed the impact of TBIL and DBIL on hematological malignancies. For this study, the inverse variance weighting method (IVW) was the primary method of MR analysis. In the sensitivity analysis, the weighted median method, MR Egger regression, and MR-PRESSO test were used. To understand the mechanisms behind TBIL and DBIL, we used three different approaches based on screening single nucleotide polymorphisms (SNPs) and their associated genes, followed by bioinformatics analysis.

Results: The IVW test results showed evidence of effects of TBIL (odds ratio [OR]: 4.47, 95% confidence interval [CI]: 1.58-12.62) and DBIL (OR: 3.31, 95% CI: 1.08-10.18) on the risk of acute myeloid leukemia (AML).The findings from bioinformatics indicated that TBIL could potentially undergo xenobiotic metabolism through cytochrome P450 and contribute to chemical carcinogenesis.

Discussion: In this study, two-sample MR analysis revealed a causal relationship between TBIL, DBIL, and AML.

Keywords: Mendelian randomized; acute myeloid leukemia; bioinformatics; direct bilirubin; hematologic malignancies; total bilirubin.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by National Natural Science Foundation of China (82000142), Natural Science Foundation of Fujian Province (2022J01735), Joint Funds for the innovation of science and Technology, Fujian province (2021Y9086,2020Y9052).