The Effects of Sun Exposure and Pigmentation Phenotype on Prognosis in Metastatic Melanoma

Authors

  • Teresa Svensson Department of Clinical Sciences Lund, Lund University Cancer Center, Lund University, Lund, Sweden; Department of Oncology, Skåne University Hospital Lund, Lund, Sweden
  • Sebastian Sahlberg Department of Clinical Sciences Lund, Lund University Cancer Center, Lund University, Lund, Sweden
  • Ana Carneiro Department of Clinical Sciences Lund, Lund University Cancer Center, Lund University, Lund, Sweden; Department of Oncology, Skåne University Hospital Lund, Lund, Sweden
  • Karolin Isaksson Department of Clinical Sciences Lund, Lund University Cancer Center, Lund University, Lund, Sweden; Department of Surgery, Skåne University Hospital Kristianstad, Kristianstad, Sweden
  • Kari Nielsen Department of Clinical Sciences Lund, Lund University Cancer Center, Lund University, Lund, Sweden; Department of Dermatology, Skåne University Hospital Lund, Lund, Sweden; Department of Dermatology, Skåne University Hospital Helsingborg, Helsingborg, Sweden https://orcid.org/0000-0002-7363-0455
  • Henrik Ekedahl Department of Clinical Sciences Lund, Lund University Cancer Center, Lund University, Lund, Sweden; Department of Oncology, Skåne University Hospital Lund, Lund, Sweden https://orcid.org/0000-0003-4337-8495

DOI:

https://doi.org/10.2340/actadv.v106.adv-2026-0388

Keywords:

immune checkpoint inhibitors, melanoma, phenotype, ultraviolet rays

Abstract

Ultraviolet radiation exposure and a fair pigmentation phenotype are well-established risk factors for primary cutaneous melanoma. However, the prognostic relevance of these risk factors is largely unexplored in metastatic disease. The aim of this study was to examine whether phenotypic characteristics and sun exposure patterns affect the prognosis of metastatic melanoma with immunotherapy available. In this retrospective study, 210 patients with stage IV melanoma were included. All patients were asked to answer a standardized questionnaire regarding risk factors for melanoma, including items on sun exposure habits and self-assessment
of phenotypic features. Survival analyses were performed with overall survival as the endpoint. Patients who reported >5 severe sunburns during childhood had a significantly decreased risk of death compared to patients with 0–1 sunburn (HR 0.46, CI 0.25–0.85, p=0.013). A fair or intermediate pigmentation phenotype was associated with a decreased risk of death compared to a dark phenotype after adjustment for distant metastasis category (HR 0.57, CI 0.34–0.93, p=0.026). This study indicates that the number of severe sunburns during childhood is associated with a more favourable prognosis in metastatic melanoma. However, due to the limited size of the study population, further research is required to confirm these results.

Downloads

Download data is not yet available.

References

Saginala K, Barsouk A, Aluru JS, Rawla P, Barsouk A. Epidemiology of melanoma. Med Sci 2021; 9: 9. DOI: https://doi.org/10.3390/medsci9040063

Gandini S, Sera F, Cattaruzza MS, Pasquini P, Picconi O, Boyle P, et al. Meta-analysis of risk factors for cutaneous melanoma: II. Sun exposure. Eur J Cancer 2005; 41: 45–60. DOI: https://doi.org/10.1016/j.ejca.2004.10.016

Sample A, He YY. Mechanisms and prevention of UV-induced melanoma. Photodermatol Photoimmunol Photomed 2018; 34: 13–24. DOI: https://doi.org/10.1111/phpp.12329

Gandini S, Sera F, Cattaruzza MS, Pasquini P, Zanetti R, Masini C, et al. Meta-analysis of risk factors for cutaneous melanoma: III. Family history, actinic damage and phenotypic factors. Eur J Cancer 2005; 41: 2040–2059. DOI: https://doi.org/10.1016/j.ejca.2005.03.034

Teixido C, Castillo P, Martinez-Vila C, Arance A, Alos L. Molecular markers and targets in melanoma. Cells 2021; 10: 2320. DOI: https://doi.org/10.3390/cells10092320

Wolchok JD, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD, et al. Long-term outcomes with nivolumab plus ipilimumab or nivolumab alone versus ipilimumab in patients with advanced melanoma. J Clin Oncol 2022; 40: 127–137. DOI: https://doi.org/10.1200/JCO.21.02229

Yang M, Brage SE, Lapins J, Grozman V, Svedman FC, Höiom V, et al. Germline MC1R variant status and efficacy of immune checkpoint inhibitors in patients with advanced melanoma. Pigment Cell Melanoma Res 2025; 38: e70050. DOI: https://doi.org/10.1111/pcmr.70050

Dousset L, Poizeau F, Robert C, Mansard S, Mortier L, Caumont C, et al. Positive association between location of melanoma, ultraviolet signature, tumor mutational burden, and response to anti-PD-1 therapy. JCO Precis Oncol 2021; 5: 5. DOI: https://doi.org/10.1200/PO.21.00084

Liu M, Li W, Ma X, Che Y, Wei B, Chen M, et al. Gradient differences of immunotherapy efficacy in metastatic melanoma related to sunlight exposure pattern: a population-based study. Front Oncol 2022; 12: 1086664. DOI: https://doi.org/10.3389/fonc.2022.1086664

Russo D, Dalle S, Dereure O, Mortier L, Dalac-Rat S, Dutriaux C, et al. Differential gradients of immunotherapy vs targeted therapy efficacy according to the sun-exposure pattern of the site of occurrence of primary melanoma: a multicenter prospective cohort study (MelBase). Front Oncol 2023; 13: 1250026. DOI: https://doi.org/10.3389/fonc.2023.1250026

Helkkula T, Christensen G, Ingvar C, Isaksson K, Harbst K, Persson B, et al. BioMEL: a translational research biobank of melanocytic lesions and melanoma. BMJ Open 2024; 14: e069694. DOI: https://doi.org/10.1136/bmjopen-2022-069694

Socialstyrelsen. Statistical database, cancer. Stockholm: Socialstyrelsen; 2025. [cited 2026 January 25]

Mao L, Qi Z, Zhang L, Guo J, Si L. Immunotherapy in acral and mucosal melanoma: current status and future directions. Front Immunol 2021; 12: 680407. DOI: https://doi.org/10.3389/fimmu.2021.680407

von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med 2007; 147: 573–577. DOI: https://doi.org/10.7326/0003-4819-147-8-200710160-00010

Westerdahl J, Anderson H, Olsson H, Ingvar C. Reproducibility of a self-administered questionnaire for assessment of melanoma risk. Int J Epidemiol 1996; 25: 245–251. DOI: https://doi.org/10.1093/ije/25.2.245

Loo K, Soliman I, Renzetti M, Li T, Wu H, Reddy S, et al. Impact of sun exposure and tanning patterns on next-generation sequencing mutations in melanoma. J Surg Res 2020; 254: 147–153. DOI: https://doi.org/10.1016/j.jss.2020.04.021

Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med 2014; 371: 2189–2199. DOI: https://doi.org/10.1056/NEJMoa1406498

Fortman D, Karunamurthy A, Hartman D, Wang H, Seigh L, Abukhiran I, et al. Automated quantitative CD8+ tumor-infiltrating lymphocytes and tumor mutation burden as independent biomarkers in melanoma patients receiving front-line anti-PD-1 immunotherapy. Oncologist 2024; 29: 619–628. DOI: https://doi.org/10.1093/oncolo/oyae054

Dwyer T, van der Mei I, Ponsonby AL, Taylor BV, Stankovich J, McKay JD, et al. Melanocortin 1 receptor genotype, past environmental sun exposure, and risk of multiple sclerosis. Neurology 2008; 71: 583–589. DOI: https://doi.org/10.1212/01.wnl.0000323928.57408.93

Newton-Bishop JA, Chang YM, Elliott F, Chan M, Leake S, Karpavicius B, et al. Relationship between sun exposure and melanoma risk for tumours in different body sites in a large case-control study in a temperate climate. Eur J Cancer 2011; 47: 732–741. DOI: https://doi.org/10.1016/j.ejca.2010.10.008

Rodvall YE, Wahlgren CF, Ullén HT, Wiklund KE. Factors related to being sunburnt in 7-year-old children in Sweden. Eur J Cancer 2010; 46: 566–572. DOI: https://doi.org/10.1016/j.ejca.2009.09.017

Robles-Espinoza CD, Roberts ND, Chen S, Leacy FP, Alexandrov LB, Pornputtapong N, et al. Germline MC1R status influences somatic mutation burden in melanoma. Nat Commun 2016; 7: 12064. DOI: https://doi.org/10.1038/ncomms12064

Tagliabue E, Gandini S, Bellocco R, Maisonneuve P, Newton-Bishop J, Polsky D, et al. MC1R variants as melanoma risk factors independent of at-risk phenotypic characteristics: a pooled analysis from the M-SKIP project. Cancer Manag Res 2018; 10: 1143–1154. DOI: https://doi.org/10.2147/CMAR.S155283

Raimondi S, Sera F, Gandini S, Iodice S, Caini S, Maisonneuve P, et al. MC1R variants, melanoma and red hair color phenotype: a meta-analysis. Int J Cancer 2008; 122: 2753–2760. DOI: https://doi.org/10.1002/ijc.23396

Gibson JAG, Dobbs TD, Griffiths R, Song J, Akbari A, Whitaker S, et al. The association of smoking and socioeconomic status on cutaneous melanoma: a population-based, data-linkage, case-control study. Br J Dermatol 2020; 182: 1136–1147. DOI: https://doi.org/10.1111/bjd.18526

Galobardes B, Shaw M, Lawlor DA, Lynch JW, Davey Smith G. Indicators of socioeconomic position (part 1). J Epidemiol Community Health 2006; 60: 7–12. DOI: https://doi.org/10.1136/jech.2004.023531

Additional Files

Published

2026-05-12

How to Cite

Svensson, T., Sahlberg, S., Carneiro, A., Isaksson, K., Nielsen, K., & Ekedahl, H. (2026). The Effects of Sun Exposure and Pigmentation Phenotype on Prognosis in Metastatic Melanoma. Acta Dermato-Venereologica, 106, adv–2026. https://doi.org/10.2340/actadv.v106.adv-2026-0388

Issue

Section

Articles

Categories