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. 2024 Oct 10:15:1460275.
doi: 10.3389/fimmu.2024.1460275. eCollection 2024.

Understanding bladder cancer risk: Mendelian randomization analysis of immune cell and inflammatory factor influence

Hiocheng Un #  1 , Wumier Wusimanjiang #  1 , Wenhao Zhan #  1 , Xinxin Zhang  1 , Minghao Li  1 , Jiahao Lei  1 , Renxuan Lin  1 , Yuliang Zhang  2 , Junxing Chen  1 , Zongren Wang  1
Affiliations

Understanding bladder cancer risk: Mendelian randomization analysis of immune cell and inflammatory factor influence

Hiocheng Un et al. Front Immunol. .

Abstract

Introduction: The intricate roles of immune cells and inflammatory factors in cancer, particularly their association with the risk of bladder cancer, are not well understood.

Methods: This study aimed to clarify potential causal relationships between these elements and the development of bladder cancer using genome-wide association study (GWAS) summary statistics for 731 immune cell phenotypes and 91 circulating inflammatory factors (cases=2,053; controls=287,137). The primary analytical approach was Inverse Variance Weighting (IVW), supplemented by MR-Egger regression, weighted median, and weighted mode analyses. Sensitivity analyses included Cochran Q test, MR-Egger intercept test, and Leave-one-out test.

Results: The findings indicated that monocytes are positively correlated with an increased risk of bladder cancer. On the contrary, double-negative (DN) T cells, HLA DR+CD8br, and CD28 on CD28+CD45RA+CD8br T cells exhibited an inverse correlation, suggesting a possible protective effect. Furthermore, inflammatory factors IL-20, IL-22RA1, and Eotaxin were significantly associated with an increased risk of bladder cancer.

Discussion: These results suggest that certain immune cell phenotypes and inflammatory factors may play a role in the development of bladder cancer and could serve as potential biomarkers for assessing tumor risk. The findings also offer new insights into the pathogenesis of bladder cancer, indicating a need for further investigation.

Keywords: GWAS; Mendelian randomization; bladder cancer; immune cell phenotypes; inflammatory factors.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer XD declared a shared parent affiliation, with no collaboration, with the authors to the handling editor at the time of the review.

Figures

Figure 1
Figure 1
Overview of the study.
Figure 2
Figure 2
MR analysis results of immune cell phenotypes and circulating inflammatory factors in relation to bladder cancer: (A) is a pie chart for the results in the inverse-variance weighting (IVW) method with p<0.01. (B) presented the results using IVW, MR Egger, Weighted median and Weighted mode method, displaying odds ratios (OR), confidence intervals (CI), and the relevant single nucleotide polymorphisms (SNPs) associated with the study.
Figure 3
Figure 3
Scatter plots according to the analysis result of MR-Egger, weighted median, and weighted mode for the causal association between immune cell phenotypes and circulating inflammatory factors and bladder cancer. Illustrated the association with a focus on the relevant single nucleotide polymorphisms (SNPs) involved.
Figure 4
Figure 4
Leave-one-out plots for the causal association between immune cell phenotypes and circulating inflammatory factors and bladder cancer. Demonstrated the stability of the causal inference through a leave-one-out methodology.
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