Association of incident amelanotic melanoma with phenotypic characteristics, MC1R status, and prior amelanotic melanoma Journal Article

Authors: Vernali, S.; Waxweiler, W. T.; Dillon, P. M.; Kanetsky, P. A.; Orlow, I.; Luo, L.; Busam, K. J.; Kricker, A.; Armstrong, B. K.; Anton-Culver, H.; Gruber, S. B.; Gallagher, R. P.; Zanetti, R.; Rosso, S.; Sacchetto, L.; Dwyer, T.; Cust, A. E.; Ollila, D. W.; Begg, C. B.; Berwick, M.; Thomas, N. E.; for the GEM Study Group
Article Title: Association of incident amelanotic melanoma with phenotypic characteristics, MC1R status, and prior amelanotic melanoma
Abstract: IMPORTANCE: We previously reported that survival is poorer from histopathologically amelanotic than pigmented melanoma because of more advanced stage at diagnosis. Identifying patients at risk of amelanotic melanoma might enable earlier diagnosis and improved survival; however, the phenotypic characteristics and underlying genetics associated with amelanotic melanoma are unknown. OBJECTIVE: To determine whether phenotypic characteristics, carriage of MC1R variants, and history of amelanotic melanoma are associated with histopathologically amelanotic melanoma. DESIGN, SETTING, AND PARTICIPANTS: The Genes, Environment, and Melanoma (GEM) study is an international cohort study that enrolled patients with incident primary cutaneous melanomas from population-based and hospital-based cancer registries (1998 to 2003). The GEM participants included here were 2387 patients with data for phenotypes, MC1R genotype, and primary melanomas scored for histopathologic pigmentation. Of these 2387 patients with incident melanomas scored for pigmentation, 527 had prior primary melanomas also scored for pigmentation. MAIN OUTCOMES AND MEASURES: Associations of phenotypic characteristics (freckles, nevi, phenotypic index) and MC1R status with incident amelanotic melanomas were evaluated using logistic regression models adjusted for age, sex, study center, and primary status (single or multiple primary melanoma); odds ratios (ORs) and 95% CIs are reported. Association of histopathologic pigmentation between incident and prior melanomas was analyzed using an exact logistic regression model. RESULTS: This study included 2387 patients (1065 women, 1322 men; mean [SD] age at diagnosis, 58.3 [16.1] years) and 2917 primary melanomas. In a multivariable model including phenotypic characteristics, absence of back nevi, presence of many freckles, and a sun-sensitive phenotypic index were independently associated with amelanotic melanoma. Carriage of MC1R variants was associated with amelanotic melanoma but lost statistical significance in a model with phenotype. Further, patients with incident primary amelanotic melanomas were more likely to have had a prior primary amelanotic melanoma (OR, 4.62; 95% CI, 1.25-14.13) than those with incident primary pigmented melanomas. CONCLUSIONS AND RELEVANCE: Absence of back nevi, presence of many freckles, a sun-sensitive phenotypic index, and prior amelanotic melanoma increase odds for development of amelanotic melanoma. An increased index of suspicion for melanoma in presenting nonpigmented lesions and more careful examination for signs of amelanotic melanoma during periodic skin examination in patients at increased odds of amelanotic melanoma might lead to earlier diagnosis and improved survival. © 2017 American Medical Association. All rights reserved.
Keywords: adult; aged; middle aged; primary tumor; major clinical study; genetics; histopathology; phenotype; gene; disease association; cohort studies; skin pigmentation; nevus; skin neoplasms; logistic models; cohort analysis; genetic association; genetic variability; genotype; pathology; heterozygote; pigmentation; skin tumor; amelanotic melanoma; statistical model; melanocortin 1 receptor; receptor, melanocortin, type 1; medical history; mc1r gene; lentigo; melanoma, amelanotic; humans; human; male; female; priority journal; article
Journal Title: JAMA Dermatology
Volume: 153
Issue: 10
ISSN: 2168-6068
Publisher: American Medical Association  
Date Published: 2017-10-01
Start Page: 1026
End Page: 1031
Language: English
DOI: 10.1001/jamadermatol.2017.2444
PUBMED: 28746718
PROVIDER: scopus
PMCID: PMC5650093
Notes: Article -- Export Date: 2 November 2017 -- Source: Scopus
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MSK Authors
  1. Colin B Begg
    241 Begg
  2. Irene Orlow
    193 Orlow
  3. Klaus J Busam
    545 Busam