Causal Relationships Between Inflammatory Factors and Multiple Myeloma: A Bidirectional Mendelian Randomization Study
Menée à l'aide d'une méthode de randomisation mendélienne et des données de deux études d'association à l'échelle du génome portant sur 372 617 personnes, cette étude analyse l'association entre la protéine C-réactive, les régulateurs inflammatoires sériques et le risque de myélome multiple
Changes in serum inflammatory factors occur throughout the onset and multiple myeloma (MM) progression, the feedback loops make it harder to distinguish between causes and effects. In the present study, we performed a bidirectional summary-level Mendelian randomization (MR) analysis to elucidate the causal relationships of C-reactive protein (CRP) and inflammatory regulators with MM. Summary-level data of genetic variants associated with inflammation were extracted from two genome-wide association studies (GWASs) on CRP and human cytokines, and MM from large meta-analyses of GWASs among 372 617 UK Biobank participants. The inverse-variance weighted (IVW) method was used as the primary MR analysis and MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO) were used as the sensitivity analyses. Our results suggest that higher levels of monocyte-specific chemokine-3[IVW estimate odds ratio (ORIVW) per standard deviation genetic cytokines change: 1.24; 95% confidence interval (CI): 1.03-1.49; P=0.02], vascular endothelial growth factor [1.14, 1.03-1.27; P=0.02], interleukin-10 [1.33, 1.01-1.75; P=0.04], and interleukin-7 [1.24, 1.03-1.48; P=0.02] were associated with increased risk of MM, while lower levels of tumor necrosis factor-β [0.84, 0.74-0.92; P<0.001] was strongly associated with an increased risk of MM. And conversely, genetically predicted MM is related to increased levels of interleukin-17 [IVW estimate β: 0.051, 95% CI: 0.018-0.085; P =2.7×10-3]. Besides, we observed no such significant associations for other inflammatory factors in this study. Overall, this study provides genetic evidence on the relationships of CRP and systemic inflammatory regulators with MM. Targeted interventions of specific inflammatory factors may have implications to alleviate MM cancer risk.