Change in Metabolic Markers and the Risk of Skin Cancer: Results from the Lifelines Cohort Study in the Netherlands

BACKGROUND: Skin-cancers are the most common cancers in Caucasians, and their incidence is rising. Although metabolic and anthropometric markers play a role in cancer development, the relationship of metabolic and anthropometric changes with skin-cancer remains unclear. This study aimed to examine possible associations between these changes and the risk of skin-cancer.

METHODS: Participants without prior skin-cancer history from the Northern-Netherlands representative of the general population were included. Histopathology data were obtained from the Dutch Nationwide Pathology-Database. Adjusted-Cox-regression analyzed associations between metabolic changes and time to pathology-confirmed skin-cancer incidence over a 7-year follow-up, assessing overall skin-cancer risk and subtypes, including melanoma and non-melanoma skin-cancer.

RESULTS: Out of 97,106 participants, 4,195 (4.3%) developed skin-cancer. Body-mass-index (BMI) decrease and increase were both associated with lower skin-cancer risk: adjusted-hazard-ratios(aHR) of 0.88(0.80-0.98) and 0.78(0.72-0.86), respectively. Triglyceride and waist-to-hip ratio (WHR)decreases were also associated with lower risk: aHR: 0.89(0.80-0.98) and 0.89(0.83-0.98), respectively. Increase in HbA1c was associated with higher risk in individuals under 45 years at baseline: aHR: 1.21(1.01-1.45). Subtype-analysis showed an increase in BMI was associated with lower melanoma risk: aHR: 0.72(0.58-0.91).

CONCLUSIONS: Changes in BMI and decrease in triglycerides and WHR are related to lower skin-cancer risk, whereas increase in HbA1c may elevate risk in individuals younger than 45 at baseline. These findings highlight the importance of non-sunlight-related risk factors for skin-cancer prevention and the need for further research into underlying mechanisms.

IMPACT: This study contributes to the broader understanding of how metabolic health impacts skin-cancer development, offering potential avenues for targeted prevention strategies.