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:
- Is melanoma risk and survival related to obesity and levels of leptin and vitamin D?
- 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.
Stenehjem JS, Grimsrud TK, Rees JR, Vos L, Babigumira R, Veierød MB, Robsahm TE. A protocol for prospective studies of 25-hydroxyvitamin D, leptin and body mass index in relation to cutaneous melanoma incidence and survival. BMJ Open. 2017 Jun 21;7(6):e014829. doi: 10.1136/bmjopen-2016-014829. PMID: 28637727; PMCID: PMC5623373.
Gislefoss RE, Stenehjem JS, Hektoen HH, Andreassen BK, Langseth H, Axcrona K, Weiderpass E, Mondul A, Robsahm TE. Vitamin D, obesity and leptin in relation to bladder cancer incidence and survival: prospective protocol study. BMJ Open. 2018 Mar 30;8(3):e019309. doi: 10.1136/bmjopen-2017-019309. PMID: 29602840; PMCID: PMC5884376.
Stenehjem JS, Veierød MB, Nilsen LT, Ghiasvand R, Johnsen B, Grimsrud TK, Babigumira R, Støer NC, Rees JR, Robsahm TE. Anthropometric factors and Breslow thickness: prospective data on 2570 cases of cutaneous melanoma in the population-based Janus Cohort. Br J Dermatol. 2018 Sep;179(3):632-641. doi: 10.1111/bjd.16825. Epub 2018 Jul 26. PMID: 29858512.
Stenehjem JS, Veierød MB, Nilsen LT, Ghiasvand R, Johnsen B, Grimsrud TK, Babigumira R, Støer NC, Rees JR, Robsahm TE. Anthropometric factors and Breslow thickness: prospective data on 2570 cases of cutaneous melanoma in the population-based Janus Cohort. Br J Dermatol. 2018 Sep;179(3):632-641. doi: 10.1111/bjd.16825. Epub 2018 Jul 26. PMID: 29858512.
Stenehjem JS, Støer NC, Ghiasvand R, Grimsrud TK, Babigumira R, Rees JR, Nilsen LT, Johnsen B, Thorsby PM, Veierød MB, Robsahm TE. Prediagnostic serum 25-hydroxyvitamin D and melanoma risk. Sci Rep. 2020 Nov 18;10(1):20129. doi: 10.1038/s41598-020-77155-2. PMID: 33208828; PMCID: PMC7676247.
Stenehjem JS, Støer NC, Ghiasvand R, Grimsrud TK, Babigumira R, Rees JR, Nilsen LT, Johnsen B, Thorsby PM, Veierød MB, Robsahm TE. Prediagnostic serum 25-hydroxyvitamin D and leptin in relation to melanoma-specific death and overall death. Pigment Cell Melanoma Res. 2022 Mar;35(2):280-284. doi: 10.1111/pcmr.13026. Epub 2022 Jan 10. PMID: 34978150.
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