Nevus Count, Pigmentary Characteristics, and Melanoma-specific Mortality among Norwegian Women with Melanoma >1.0 mm Thick
Keywords:awareness, epidemiology, neoplasms, Nevus, melanoma, mortality, pigmentation
Little is known about if and how nevi and pigmentation are associated with melanoma-specific mortality. However, increased melanoma awareness in people with lighter pigmentation and many nevi may result in earlier diagnosis of thinner less-lethal tumors. The aim of this study was to investigate associations between nevus count (asymmetrical > 5 mm and small symmetrical), pigmentary characteristics (hair colour, eye colour, skin colour, freckling, pigmentary score), and melanoma-specific mortality in subjects with melanomas > 1 mm. Data from the Norwegian Women and Cancer cohort, established in 1991, with complete follow-up of melanoma patients until 2018 through the Cancer Registry of Norway, were used to estimate hazard ratios with 95% confidence intervals for the associations between nevus count, pigmentary characteristics, and melanoma-specific mortality, stratified by tumor thickness using Cox regression. Estimated hazard ratios consistently indicated a higher risk of melanoma death for those with darker vs lighter pigmentary characteristics in patients with tumors > 1.0–2.0 mm and > 2.0 mm thick (e.g. pigmentary score hazard ratio 1.25, 95% confidence interval (0.74–2.13)). Among women with melanomas > 1.0 mm thick, lighter pigmentation and asymmetrical nevi may be associated with lower melanoma-specific mortality, suggesting that factors that increase the risk of melanoma may also be associated with decreased risk of death from melanoma.
Berwick M, Buller DB, Cust A, Gallagher R, Lee TK, Meyskens F, et al. Melanoma epidemiology and prevention. Cancer Treat Res 2016; 167: 17-49.
https://doi.org/10.1007/978-3-319-22539-5_2 DOI: https://doi.org/10.1007/978-3-319-22539-5_2
Pho LN, Leachman SA. Genetics of pigmentation and melanoma predisposition. G Ital Dermatol Venereol 2010; 145: 37-45.
Whiteman DC, Brown RM, Purdie DM, Hughes M-C. Melanocytic nevi in very young children: The role of phenotype, sun exposure, and sun protection. J Am Acad Dermatol 2005; 52: 40-47.
https://doi.org/10.1016/j.jaad.2004.07.053 DOI: https://doi.org/10.1016/j.jaad.2004.07.053
Davies JR, Randerson-Moor J, Kukalizch K, Harland M, Kumar R, Madhusudan S, et al. Inherited variants in the MC1R gene and survival from cutaneous melanoma: a BioGenoMEL study. Pigment Cell Melanoma Res 2012; 25: 384-394.
https://doi.org/10.1111/j.1755-148X.2012.00982.x DOI: https://doi.org/10.1111/j.1755-148X.2012.00982.x
Duffy DL, Iles MM, Glass D, Zhu G, Barrett JH, Höiom V, et al. IRF4 variants have age-specific effects on nevus count and predispose to melanoma. Am J Hum Genet 2010; 87: 6-16.
https://doi.org/10.1016/j.ajhg.2010.05.017 DOI: https://doi.org/10.1016/j.ajhg.2010.05.017
Ribero S, Davies JR, Requena C, Carrera C, Glass D, Rull R, et al. High nevus counts confer a favorable prognosis in melanoma patients. Int J Cancer 2015; 137: 1691-1698.
https://doi.org/10.1002/ijc.29525 DOI: https://doi.org/10.1002/ijc.29525
Rachakonda S, Srinivas N, Mahmoudpour SH, Garcia-Casado Z, Requena C, Traves V, et al. Telomere length and survival in primary cutaneous melanoma patients. Sci Rep 2018; 8: 10947.
https://doi.org/10.1038/s41598-018-29322-9 DOI: https://doi.org/10.1038/s41598-018-29322-9
Liu W, Dowling JP, Murray WK, McArthur GA, Thompson JF, Wolfe R, et al. Rate of growth in melanomas: characteristics and associations of rapidly growing melanomas. Arch Dermatol 2006; 142: 1551-1558.
https://doi.org/10.1001/archderm.142.12.1551 DOI: https://doi.org/10.1001/archderm.142.12.1551
Taylor NJ, Thomas NE, Anton-Culver H, Armstrong BK, Begg CB, Busam KJ, et al. Nevus count associations with pigmentary phenotype, histopathological melanoma characteristics and survival from melanoma. Int J Cancer 2016; 139: 1217-1222.
https://doi.org/10.1002/ijc.30157 DOI: https://doi.org/10.1002/ijc.30157
Li W-Q, Cho E, Weinstock MA, Li S, Stampfer MJ, Qureshi AA. Cutaneous nevi and risk of melanoma death in women and men: a prospective study. J Am Acad Dermatol 2019; 80: 1284-1291.
https://doi.org/10.1016/j.jaad.2018.12.058 DOI: https://doi.org/10.1016/j.jaad.2018.12.058
Ghiasvand R, Green AC, Sandanger TM, Weiderpass E, Robsahm TE, Veierød MB. Phenotypic characteristics and melanoma thickness in women. Acta Derm Venereol 2021; 101: adv00446.
https://doi.org/10.2340/00015555-3806 DOI: https://doi.org/10.2340/00015555-3806
Baumert J, Plewig G, Volkenandt M, Schmid-Wendtner MH. Factors associated with a high tumor thickness in patients with melanoma. Br J Dermatol 2007; 156: 938-944.
https://doi.org/10.1111/j.1365-2133.2007.07805.x DOI: https://doi.org/10.1111/j.1365-2133.2007.07805.x
Mishra K, Barnhill RL, Paddock LE, Fine JA, Berwick M. Histopathologic variables differentially affect melanoma survival by age at diagnosis. Pigment Cell Melanoma Res 2019; 32: 593-600.
https://doi.org/10.1111/pcmr.12770 DOI: https://doi.org/10.1111/pcmr.12770
Rosso S, Sera F, Segnan N, Zanetti R. Sun exposure prior to diagnosis is associated with improved survival in melanoma patients: results from a long-term follow-up study of Italian patients. Eur J Cancer 2008; 44: 1275-1281.
https://doi.org/10.1016/j.ejca.2008.03.009 DOI: https://doi.org/10.1016/j.ejca.2008.03.009
Berwick M, Armstrong BK, Ben-Porat L, Fine J, Kricker A, Eberle C, et al. Sun exposure and mortality from melanoma. J Natl Cancer Inst 2005; 97: 195-199.
https://doi.org/10.1093/jnci/dji019 DOI: https://doi.org/10.1093/jnci/dji019
Paddock LE, Lu SE, Bandera EV, Rhoads GG, Fine J, Paine S, et al. Skin self-examination and long-term melanoma survival. Melanoma Res 2016; 26: 401-408.
https://doi.org/10.1097/CMR.0000000000000255 DOI: https://doi.org/10.1097/CMR.0000000000000255
Autier P, Funck-Brentano E, Aegerter P, Boniol M, Saiag P. Re: High nevus counts confer a favorable prognosis in melanoma patients by S ribero and co-workers, published in the International Journal of Cancer, 2015 (online 21 march 2015). Int J Cancer 2015; 137: 3006-3007.
https://doi.org/10.1002/ijc.29648 DOI: https://doi.org/10.1002/ijc.29648
Oliveria SA, Christos PJ, Halpern AC, Fine JA, Barnhill RL, Berwick M. Evaluation of factors associated with skin self-examination. Cancer Epidemiol Biomarkers Prev 1999; 8: 971-978.
Olsen CM, Thompson BS, Green AC, Neale RE, Whiteman DC, Sun ftQ, et al. Sun protection and skin examination practices in a setting of high ambient solar radiation: a population-based cohort study. JAMA Dermatol 2015; 151: 982-990.
https://doi.org/10.1001/jamadermatol.2015.0739 DOI: https://doi.org/10.1001/jamadermatol.2015.0739
Eriksson H, Lyth J, Månsson-Brahme E, Frohm-Nilsson M, Ingvar C, Lindholm C, et al. Low level of education is associated with later stage at diagnosis and reduced survival in cutaneous malignant melanoma: a nationwide population-based study in Sweden. Eur J Cancer 2013; 49: 2705-2716.
https://doi.org/10.1016/j.ejca.2013.03.013 DOI: https://doi.org/10.1016/j.ejca.2013.03.013
Watts CG, McLoughlin K, Goumas C, van Kemenade CH, Aitken JF, Soyer HP, et al. Association between melanoma detected during routine skin checks and mortality. JAMA Dermatol 2021; 157: 1425-1436.
https://doi.org/10.1001/jamadermatol.2021.3884 DOI: https://doi.org/10.1001/jamadermatol.2021.3884
De Giorgi V, Scarfi F, Gori A, Maida P, Trane L, Silvestri F, et al. Nevi and Breslow thickness in melanoma: sex differences? Melanoma Res 2020; 30: 179-184.
https://doi.org/10.1097/CMR.0000000000000579 DOI: https://doi.org/10.1097/CMR.0000000000000579
Li WQ, Cho E, Wu S, Li S, Matthews NH, Qureshi AA. Host Characteristics and risk of incident melanoma by breslow thickness. Cancer Epidemiol Biomarkers Prev 2019; 28: 217-224.
https://doi.org/10.1158/1055-9965.EPI-18-0607 DOI: https://doi.org/10.1158/1055-9965.EPI-18-0607
Lund E, Dumeaux V, Braaten T, Hjartåker A, Engeset D, Skeie G, et al. Cohort profile: The Norwegian Women and Cancer Study - NOWAC - Kvinner og kreft. Int J Epidemiol 2008; 37: 36-41.
https://doi.org/10.1093/ije/dym137 DOI: https://doi.org/10.1093/ije/dym137
Cancer Registry of Norway. Cancer in Norway 2020 - Cancer incidence, mortality, survival and prevalence in Norway. Oslo: Cancer Registry of Norway, 2021.
Veierød MB, Parr CL, Lund E, Hjartåker A. Reproducibility of self-reported melanoma risk factors in a large cohort study of Norwegian women. Melanoma Res 2008; 18: 1-9.
https://doi.org/10.1097/CMR.0b013e3282f120d2 DOI: https://doi.org/10.1097/CMR.0b013e3282f120d2
World Health Organization. (1957). Manual of the international statistical classification of diseases, injuries, and causes of death : based on the recommendations of the seventh revision Conference, 1955, and adopted by the ninth World Health Assembly under the WHO Nomenclature Regulations. World Health Organization. https://apps.who.int/iris/handle/10665/42900.
World Health Organization. (2013). International classification of diseases for oncology (ICD-O), 3rd ed., 1st revision. World Health Organization. https://apps.who.int/iris/handle/10665/96612.
Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA Cancer J Clin 2017; 67: 93-99.
https://doi.org/10.3322/caac.21388 DOI: https://doi.org/10.3322/caac.21388
Veierød MB, Weiderpass E, Thörn M, Hansson J, Lund E, Armstrong B, et al. A prospective study of pigmentation, sun exposure, and risk of cutaneous malignant melanoma in women. J Natl Cancer Inst 2003; 95: 1530-1538.
https://doi.org/10.1093/jnci/djg075 DOI: https://doi.org/10.1093/jnci/djg075
Damsky WE, Theodosakis N, Bosenberg M. Melanoma metastasis: new concepts and evolving paradigms. Oncogene 2014; 33: 2413-2422.
https://doi.org/10.1038/onc.2013.194 DOI: https://doi.org/10.1038/onc.2013.194
Seviiri M, Scolyer RA, Bishop DT, Newton-Bishop JA, Iles MM, Lo SN, et al. Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting. J Transl Med 2022; 20: 403.
https://doi.org/10.1186/s12967-022-03613-2 DOI: https://doi.org/10.1186/s12967-022-03613-2
Ainger SA, Jagirdar K, Lee KJ, Soyer HP, Sturm RA. Skin pigmentation genetics for the clinic. Dermatology 2017; 233: 1-15.
https://doi.org/10.1159/000468538 DOI: https://doi.org/10.1159/000468538
Lira FE, Podlipnik S, Potrony M, Tell-Martí G, Calbet-Llopart N, Barreiro A, et al. Inherited MC1R variants in patients with melanoma are associated with better survival in women. Br J Dermatol 2020; 182: 138-146.
https://doi.org/10.1111/bjd.18024 DOI: https://doi.org/10.1111/bjd.18024
Kadekaro AL, Leachman S, Kavanagh RJ, Swope V, Cassidy P, Supp D, et al. Melanocortin 1 receptor genotype: an important determinant of the damage response of melanocytes to ultraviolet radiation. FASEB J 2010; 24: 3850-3860.
https://doi.org/10.1096/fj.10-158485 DOI: https://doi.org/10.1096/fj.10-158485
Rayner JE, McMeniman EK, Duffy DL, De'Ambrosis B, Smithers BM, Jagirdar K, et al. IRF4 rs12203592*T/T genotype is associated with nodular melanoma. Melanoma Res 2019; 29: 445-446.
https://doi.org/10.1097/CMR.0000000000000596 DOI: https://doi.org/10.1097/CMR.0000000000000596
Thøgersen H, Møller B, Robsahm TE, Babigumira R, Aaserud S, Larsen IK. Differences in cancer survival between immigrants in Norway and the host population. Int J Cancer 2018; 143: 3097-3105.
https://doi.org/10.1002/ijc.31729 DOI: https://doi.org/10.1002/ijc.31729
Stensrud MJ, Valberg M, Røysland K, Aalen OO. Exploring selection bias by causal frailty models: the magnitude matters. Epidemiol 2017; 28: 379-386.
https://doi.org/10.1097/EDE.0000000000000621 DOI: https://doi.org/10.1097/EDE.0000000000000621
Mucci LA, Hjelmborg JB, Harris JR, Czene K, Havelick DJ, Scheike T, et al. Familial risk and heritability of cancer among twins in Nordic countries. JAMA 2016; 315: 68-76.
https://doi.org/10.1001/jama.2015.17703 DOI: https://doi.org/10.1001/jama.2015.17703
Jacobsen KD, Akslen LA, Busch C, Bachmann IM, Fjøsne HE, Helsing P, et al. National action program with guidelines for diagnostics, treatment and follow-up of malignant melanomas. Oslo, Norway: Norwegian Directorate of Health, 2019.
Veierød MB, Page CM, Aaserud S, Bassarova A, Jacobsen KD, Helsing P, et al. Melanoma staging: varying precision and terminal digit clustering in Breslow thickness data is evident in a population-based study. J Am Acad Dermatol 2018; 79: 118-125.e1.
https://doi.org/10.1016/j.jaad.2018.03.023 DOI: https://doi.org/10.1016/j.jaad.2018.03.023
Lindholm C, Andersson R, Dufmats M, Hansson J, Ingvar C, Möller T, et al. Invasive cutaneous malignant melanoma in Sweden, 1990-1999. A prospective, population-based study of survival and prognostic factors. Cancer 2004; 101: 2067-2078.
https://doi.org/10.1002/cncr.20602 DOI: https://doi.org/10.1002/cncr.20602
Chen ML, de Vere Hunt IJ, John EM, Weinstock MA, Swetter SM, Linos E. Differences in thickness-specific incidence and factors associated with cutaneous melanoma in the US from 2010 to 2018. JAMA Oncol 2022; 8: 755-759.
https://doi.org/10.1001/jamaoncol.2022.0134 DOI: https://doi.org/10.1001/jamaoncol.2022.0134
How to Cite
Copyright (c) 2023 Ashley Ahimbisibwe, Morten Valberg, Adele C. Green, Reza Ghiasvand, Corina S. Rueegg, Raju Rimal, Elisabete Weiderpass, Torkjel M. Sandanger, Trude E. Robsahm, Marit B. Veierød
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All digitalized ActaDV contents is available freely online. The Society for Publication of Acta Dermato-Venereologica owns the copyright for all material published until volume 88 (2008) and as from volume 89 (2009) the journal has been published fully Open Access, meaning the authors retain copyright to their work.
Unless otherwise specified, all Open Access articles are published under CC-BY-NC licences, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material for non-commercial purposes, provided proper attribution to the original work.