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PLoS One. 2015 Mar 19;10(3):e0119920. doi: 10.1371/journal.pone.0119920. eCollection 2015.

Inherited variation at MC1R and histological characteristics of primary melanoma.

Author information

1
Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, United States of America.
2
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
3
Women's College Hospital, Toronto, Ontario, Canada.
4
Departments of Dermatology, Pathology and Laboratory Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America.
5
Department of Epidemiology, University of California, Irvine, California, United States of America.
6
Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia.
7
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
8
International Agency for Cancer Research, Lyon, France.
9
British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
10
Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California, United States of America.
11
Piedmont Tumor Registry, Turin, Italy.
12
Department of Dermatology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America.
13
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.
14
Departments of Internal Medicine and Dermatology, University of New Mexico, Albuquerque, New Mexico, United States of America.

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.

PMID:
25790105
PMCID:
PMC4366050
DOI:
10.1371/journal.pone.0119920
[Indexed for MEDLINE]
Free PMC Article

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