Cutaneous Melanoma and 486 Human Blood Metabolites: A Mendelian Randomization Study.

BACKGROUND

Cutaneous melanoma (CM) has long been recognized as a lethal form of cancer. Despite persistent research endeavors, the precise underlying pathological mechanisms remain largely unclear, and the optimal treatment for this patient population remains undetermined.

OBJECTIVES

This study aims to examine the causal associations between CM and 486 metabolites.

METHODS

A two-sample Mendelian randomization (MR) analysis was conducted to ascertain the causal relationship between blood metabolites and CM. The causality analysis involved the inverse variance weighted (IVW) method, followed by the MR-Egger and weighted median (WM) methods. To increase the robustness of our findings, several sensitivity analyses, including the MR-Egger intercept, Cochran's Q test, and MR-pleiotropy residual sum and outlier (MR-PRESSO), were performed. The robustness of our results was further validated in independent outcome samples followed by a meta-analysis. Additionally, a metabolic pathway analysis was carried out.

RESULTS

The two-sample MR analysis yielded a total of 27 metabolites as potential causal metabolites. After incorporating the outcomes of the sensitivity analyses, seven causal metabolites remained. Palmitoylcarnitine (OR 0.9903 95% CI 0.9848-0.9958, p = 0.0005) emerged as the sole metabolite with a significant causality after Bonferroni correction. Furthermore, the reverse MR analysis provided no evidence of reverse causality from CM to the identified metabolites.

CONCLUSIONS

This study suggested a causal relationship between seven human blood metabolites and the development of CM, thereby offering novel insights into the underlying mechanisms involved.

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