Is metabolic syndrome a risk factor for skin cancer? A UKBiobank Observational and two Sample Mendelian randomization Study

Abstract Background: Skin cancers (SCs) are the third most common cancer worldwide, with incidence increasing. Metabolic syndrome (MetS) is a cluster of metabolic abnormalities strongly associated with the development of cardiovascular disease. More than 1 in 5 individuals have MetS and it is linked with at least 14 different cancers. This study aimed to investigate whether MetS is a risk factor for SC. Methods: A prospective cohort study was conducted in UK Biobank. The association between MetS and SC was investigated using multivariable Poisson regression. To investigate causality, a two sample Mendelian randomization (MR) study was conducted using summary level Genome-wide association study data from UK Biobank (MetS) and FinnGen (SC). Results: 467,919 participants were included, 26.7% had MetS. Follow-up was for up to 10.8 years. MetS showed a moderately sized protective effect on BCC while the effect for SCC and MM crossed the null. Overall, MR found there was some weak evidence for increase odds of SC in those with MetS (1.07 (OR = 1.07 (95% CI: 1.01, 1.14)). Conclusions= The observational study identifies a moderately sized protective effect of MetS on BCC with MR evidence suggesting a weak causal effect is in the opposite direction. Impact: This study has found little to no effect of MetS on SC, despite links between MetS and at least 14 other cancers.