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

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.

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).

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.

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.