title: Inherited variation at MC1R and histological characteristics of primary melanoma.
abstract: Variation in the melanocortin-1receptor (MC1R) gene is associated with pigmentary phenotypes and risk of malignant melanoma. Few studies have reported on MC1R variation with respect to tumor characteristics, especially clinically important prognostic features. We examined associations between MC1R variants and histopathological melanoma characteristics. Study participants were enrolled from nine geographic regions in Australia, Canada, Italy and the United States and were genotyped for MC1R variants classified as high-risk [R] (D84E, R142H, R151C, R160W, and D294H, all nonsense and insertion/deletion) or low-risk [r] (all other nonsynonymous) variants. Tissue was available for 2,160 white participants of the Genes, Environment and Melanoma (GEM) Study with a first incident primary melanoma diagnosis, and underwent centralized pathologic review. No statistically significant associations were observed between MC1R variants and AJCC established prognostic tumor characteristics: Breslow thickness, presence of mitoses or presence of ulceration. However, MC1R was significantly associated with anatomic site of melanoma (p = 0.002) and a positive association was observed between carriage of more than one [R] variant and melanomas arising on the arms (OR = 2.39; 95% CI: 1.40, 4.09). We also observed statistically significant differences between sun-sensitive and sun-resistant individuals with respect to associations between MC1R genotype and AJCC prognostic tumor characteristics. Our results suggest inherited variation in MC1R may play an influential role in anatomic site presentation of melanomas and may differ with respect to skin pigmentation phenotype.
authors: Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, United States of America.
authors: Nicholas J
authors: NJ
authors: Taylor
authors: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors: Klaus J
authors: KJ
authors: Busam
authors: Women's College Hospital, Toronto, Ontario, Canada.
authors: Lynn
authors: L
authors: From
authors: Departments of Dermatology, Pathology and Laboratory Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors: Pamela A
authors: PA
authors: Groben
authors: Department of Epidemiology, University of California, Irvine, California, United States of America.
authors: Hoda
authors: H
authors: Anton-Culver
authors: Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia.
authors: Anne E
authors: AE
authors: Cust
authors: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors: Colin B
authors: CB
authors: Begg
authors: International Agency for Cancer Research, Lyon, France.
authors: Terence
authors: T
authors: Dwyer
authors: British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors: Richard P
authors: RP
authors: Gallagher
authors: Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California, United States of America.
authors: Stephen B
authors: SB
authors: Gruber
authors: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors: Irene
authors: I
authors: Orlow
authors: Piedmont Tumor Registry, Turin, Italy.
authors: Stefano
authors: S
authors: Rosso
authors: Department of Dermatology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors: Nancy E
authors: NE
authors: Thomas
authors: Piedmont Tumor Registry, Turin, Italy.
authors: Roberto
authors: R
authors: Zanetti
authors: Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Timothy R
authors: TR
authors: Rebbeck
authors: Departments of Internal Medicine and Dermatology, University of New Mexico, Albuquerque, New Mexico, United States of America.
authors: Marianne
authors: M
authors: Berwick
authors: Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, United States of America.
authors: Peter A
authors: PA
authors: Kanetsky
mesh_terms: D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D012307:Risk Factors; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D012880:Skin Pigmentation / Q000235:genetics
chemical_list: D044102:Receptor, Melanocortin, Type 1