Causal relationship between genetically determined plasma metabolites and skin cancer: a two-sample Mendelian randomization study.

Abstract

We aimed to unveil the underlyingpathogenic mechanismsof skin cancer inrelation tometabolic factors and pathway mechanisms. This studyutilized the TwoSample Mendelian randomization (MR) method to investigatethe causalrelationshipbetween 1400 plasma metabolites and skin cancer. The primary method employed was the inverse variance weighting (IVW). ThroughIVW analysis, wefound 105 plasma metabolitesassociatedwith Basal Cell Carcinoma (BCC),withthe highestassociationobserved forProlylglycine levels (OR [95% CI]: 1.1902 [1.0274, 1.3788]). For Malignant Melanoma of Skin (MSS),68 plasma metabolites werelinked, with the highestcausal relationship seen for3-Hydroxybutyrate levels (OR [95% CI]: 1.0030 [1.0013, 1.0048]). Regarding actinic keratosis (AK),and the highest association observed forHexadecadienoate (16:2n6) levels (OR [95% CI]: 1.3302 [1.0333, 1.7125]).Glycerol to palmitoylcarnitine (16: n6) levels (OR [95% CI]: 1.3302 [1.0333, 1.125]) werefound to be significant for BCC and AK.Palmitoylcarnitine (C16) had themost positive causal effect for BCC (OR [95% CI]: 1.1777 [1.0493, 1.3218]),while5-hydroxy-2-methylpyridine sulfate levelshad the highest effectfor AK (OR [95% CI]:1.1788 [1.0295, 1.3498]).And 4-guanidinobutanoate levels had the largest positive causal effect (OR [95% CI]: 1.0857 [1.0417, 1.1317]) for BCC, and X-11880 levels for MSS(OR [95% CI]: 1.0013 [1.0000, 1.0025]). The study revealed a positive association betweenhereditary Glycerol to palmitoylcarnitine (C16) and 5-hydroxy-2-methylpyridine sulfate levelswith the risk of developing BCC and AK. Additionally,4-guanidinobutanoate levels and X 11880 levels werefound to bepositively associated with the risk of BCC and MMS.