Vitamin D, obesity and cutaneous malignant melanoma

Background and purpose

Melanoma is among the cancer types with the fastest increasing incidence in Norway. Patients with a history of melanoma also have an increased risk of developing a new primary cancer, especially lymphoma, suggesting a potential shared etiological background. The rise in melanoma incidence is primarily linked to tanning habits and exposure to ultraviolet (UV) radiation. However, other factors, in conjunction with UV radiation, could also play a role. Concurrently with the increase in melanoma occurrence, the proportion of overweight individuals in the population has risen. Obesity is associated with an increased risk of several cancer types through various mechanisms that could also influence melanoma development. Obesity is linked to low levels of vitamin D and high levels of leptin, both of which could contribute to the progression of melanoma.

The purpose of this project is to study melanoma etiology by addressing the following questions:

1. Is melanoma risk and survival related to obesity and levels of leptin and vitamin D?
2. Is the risk of a new primary cancer, following melanoma, related to levels of leptin and vitamin D?

Data source

The project is based on data from population-based health surveys and serum samples from the Janus Serum Bank Cohort, covering nearly 300,000 Norwegians, with cancer data from the Cancer Registry, cause of death data from the Cause of Death Registry, and information on education and occupation from Statistics Norway. The project includes cohort studies based on health surveys and case-control studies based on serum samples from the Janus Serum Bank.

Results 

We found positive associations between height, weight, body mass index (BMI), and body surface area (BSA) and the risk of melanoma, with weight reduction decreasing the risk. The association is stronger for men than for women, which could be attributed to different tanning behaviors between overweight men and women. Similarly, we found positive associations between height, weight, BMI, and BSA, and tumor thickness (Breslow thickness), supporting the potential role of obesity in melanoma development.

Based on prediagnostic levels of vitamin D (25(OH)D), we observed a J-shaped relationship between vitamin D and melanoma risk, where a sufficient level (60-85 nmol/L) is associated with reduced risk. UV exposure is the primary causative factor for melanoma and the main source of vitamin D. Stratified analyses indicate that BMI and UV exposure could mediate this relationship.

Furthermore, we found that low prediagnostic levels of vitamin D were associated with increased tumor thickness and increased risk of melanoma-specific death, while increasing leptin levels were associated with an elevated risk of melanoma-specific death and overall mortality. This was particularly pronounced for thicker tumors (T3-T4). The results suggest that leptin could be a prognostic marker for melanoma, but these findings should be validated in studies with multiple measurements, including serum samples taken before, during, and after diagnosis.