Association between inflammatory factors and melanoma: a bidirectional Mendelian randomization study.

Abstract

Purpose: This study performed a bidirectional Mendelian randomization (MR) analysis to elucidate the causal relationships of C-reactive protein and 41 inflammatory regulators with melanoma, including data from UK Biobank, Cardiovascular Risk in Young Finns Study, and Cohorts for Inflammation Work Group.

Methods: We selected the inverse variance weighting (IVW) to merge the estimated causal effects of multiple SNPs into a weighted average. To evaluate the heterogeneities of IVW, the Cochran Q statistic, and I² index were used. What's more, several sensitivity analyses were employed, including IVW, MR-Egger, weighted median, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO).

Results: With SNPs reaching P < 5 × 10^-8, the analyses findings revealed that IL-16 had a significant positively association with genetically risk of melanoma (OR_IVW: 1.05; 95% CI: 1.03-1.07; P < 0.001), and high levels of MCP1 (OR_IVW: 1.13; 95% CI: 1.03-1.23; P = 0.01) were suggestively associated with melanoma susceptibility. What's more, TNF-β (OR_IVW: 1.07; 95% CI: 1.01-1.13; P = 0.02) and IL-8 (OR_IVW: 1.08, 95% CI: 1.01-1.16; P = 0.03) were demonstrated a positive association with the risk of melanoma under a less stringent cut-off (P < 5 × 10^-6). Conversely, we found a facilitative effect of melanoma susceptibility on IP-10 and inhibitory effects on IL-6, IL-1b, and GRO-α.

Conclusion: The genetic evidence that we have uncovered indicates a potential association between the levels of specific inflammatory markers (IL-16, IL-8, MCP-1, and TNF-β) and the risk of melanoma. Further research is imperative to translate these findings into clinical applications.