Blood metabolites mediate the causal relationship between circulating CX3CL1 levels and prostate cancer: A 2-step Mendelian randomization study

Author:

Zhou Yinshu1,Chen Zheng1,Guo Zexiong1,Gao Guie2,Duan Yiping3,Wang Haoyu4,Sun Luping1,Huang Wanwei1,Zhuo Yumin1ORCID

Affiliation:

1. Department of Urology, The First Affiliated Hospital of Jinan University, Guangzhou, China

2. Surgery Center, The First Affiliated Hospital of Jinan University, Guangzhou, China

3. School of Basic Medicine and Public Health, Jinan University, Guangzhou, China

4. International School, Jinan University, Guangzhou, China.

Abstract

Chemokines influence the progression of prostate cancer (PCa) through multiple mechanisms. However, the effect of C-X3-C chemokine ligand 1 (CX3CL1) on PCa risk remains controversial. Our study aimed to investigate whether circulating CX3CL1 is causally associated with PCa and to identify metabolites that have mediating effects using the 2-step bidirectional Mendelian randomization (MR) analysis process. Inverse variance weighting (IVW) results were used as the primary observations, while additional sensitivity analyses were conducted. For each standard deviation increase exhibited by the circulating CX3CL1 levels, the risk of PCa was reduced by 0.4% (IVW: OR = 0.996, [95% CI = 0.994–0.998], P < .001), and blood alliin levels increased by 19% (IVW: OR = 1.185, [95% CI = 1.01–1.54], P = .003). For each standard deviation increase in the blood alliin levels, the risk of PCa was reduced by 0.1% (IVW: OR = 0.999, [95% CI = 0.997–0.999], P = .03). Therefore, the protective effect of circulating CX3CL1 on PCa may be mediated by blood alliin levels (mediated proportion = 6.7%). The results supported the notion that high levels of circulating CX3CL1 indicate a lower PCa risk and the idea that the food-derived antioxidant alliin may mediate this association. We emphasize that the use of CX3CL1 as a protective factor against PCa may provide new strategies for PCa prevention and care in the future.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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