Is Metabolic Syndrome a Risk Factor for Skin Cancer? A UK Biobank Observational and Two-Sample Mendelian Randomization Study.

BACKGROUND

Skin cancers 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 one in five 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 skin cancer.

METHODS

A prospective cohort study was conducted in the UK Biobank. The association between MetS and skin cancer 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 the UK Biobank (MetS) and FinnGen (skin cancer).

RESULTS

A total of 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 basal-cell carcinoma, whereas the effect for squamous cell carcinoma and malignant melanoma crossed the null. Overall, MR found there was some weak evidence for increased odds of skin cancer in those with MetS [OR = 1.07 (95% confidence interval: 1.01, 1.14)].

CONCLUSIONS

The observational study identifies a moderately sized protective effect of MetS on basal-cell carcinoma with MR evidence suggesting a weak causal effect in the opposite direction.

IMPACT: This study has found little-to-no effect of MetS on skin cancer despite links between MetS and at least 14 other cancers.