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

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 between metabolic and anthropometric changes in skin cancer remains unclear. This study aimed to examine possible associations between these changes and the risk of skin cancer.

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 nonmelanoma skin cancer.

Out of 97,106 participants, 4,195 (4.3%) developed skin cancer. Decrease and increase in body mass index (BMI) were both associated with lower skin cancer risk: adjusted HRs (aHR) of 0.88 (0.80-0.98) and 0.78 (0.72-0.86), respectively. Triglyceride and waist-to-hip ratio decreases were also associated with lower risk: aHR: 0.89 (0.80-0.98) and 0.89 (0.83-0.98), respectively. Increase in Hemoglobin A1c (HbA1c) was associated with a higher risk in individuals below the age of 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).

Changes in BMI and decrease in triglycerides and waist-to-hip ratio are related to lower skin cancer risk, whereas an 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.

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