Mendelian Randomization Analysis Supports a Causal Relationship Between Circulating Inflammatory Proteins and Basal Cell Carcinoma

Background
It has been shown that the Basal cell carcinoma (BCC) is associated with chronic inflammation of skin conditions, the circulating inflammatory protein levels may be a more intuitive index in response to inflammation, however, the cause-and-effect relationship between circulating inflammatory proteins and BCC is currently unknown.

Methods
This study performed a Mendelian randomization (MR) analysis using the plasma inflammatory protein levels from a large genome-wide protein quantitative trait loci study as the exposure data, and the outcome data from a GWAS for BCC. Inverse variance weighed, MR-Egger, maximum likelihood ratio, and weighted median for assessing causality between inflammatory proteins and BCC. MR-Egger regression and Cochran’s Q statistic were applied for sensitivity analysis and MRPRESSO was applied to exclude outliers. Inverse MR analysis was performed on inflammatory proteins found to be causally associated with BCC.

Results
Six circulating inflammatory proteins with a causal relationship with BCC were obtained, including CCL4, was of a significant protective effect on BCC development. IL-18 and CCL28, were of suggestive protective effects on BCC development. CX3CL1, IL-17A, and CSF-1 were potential risk factors in the development of BCC. According to the results of reverse MR analysis, there is no significant causal relationship between BCC and the above-mentioned inflammatory proteins.

Conclusion
This two-sample MR study revealed a strong association between circulating inflammatory proteins and the development of BCC. Specifically, CCL4, CCL28, IL-18, CX3CL1, IL-17A, and CSF-1 emerged as potential targets for prognostic evaluation and treatment of BCC. However, further experimental studies are needed to elucidate the specific mechanisms.