title: Genetic markers of pigmentation are novel risk loci for uveal melanoma.
abstract: While the role of genetic risk factors in the etiology of uveal melanoma (UM) has been strongly suggested, the genetic susceptibility to UM is currently vastly unexplored. Due to shared epidemiological risk factors between cutaneous melanoma (CM) and UM, in this study we have selected 28 SNPs identified as risk variants in previous genome-wide association studies on CM or CM-related host phenotypes (such as pigmentation and eye color) and tested them for association with UM risk. By logistic regression analysis of 272 UM cases and 1782 controls using an additive model, we identified five variants significantly associated with UM risk, all passing adjustment for multiple testing. The three most significantly associated variants rs12913832 (OR = 0.529, 95% CI 0.415-0.673; p = 8.47E-08), rs1129038 (OR = 0.533, 95% CI 0.419-0.678; p = 1.19E-07) and rs916977 (OR = 0.465, 95% CI 0.339-0.637; p = 3.04E-07) are correlated (r(2) > 0.5) and map at 15q12 in the region of HERC2/OCA2, which determines eye-color in the human population. Our data provides first evidence that the genetic factors associated with pigmentation traits are risk loci of UM susceptibility.
authors: Perlmutter Cancer Center, New York University School of Medicine, New York, USA.|Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, USA.|The Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, USA.
authors: Robert
authors: R
authors: Ferguson
authors: Perlmutter Cancer Center, New York University School of Medicine, New York, USA.|Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, USA.|The Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, USA.
authors: Matjaz
authors: M
authors: Vogelsang
authors: Perlmutter Cancer Center, New York University School of Medicine, New York, USA.|Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, USA.|The Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, USA.
authors: Esma
authors: E
authors: Ucisik-Akkaya
authors: Division of Human Genetics, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
authors: Karan
authors: K
authors: Rai
authors: Division of Human Genetics, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
authors: Robert
authors: R
authors: Pilarski
authors: Perlmutter Cancer Center, New York University School of Medicine, New York, USA.|Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, USA.|The Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, USA.
authors: Carlos N
authors: CN
authors: Martinez
authors: Perlmutter Cancer Center, New York University School of Medicine, New York, USA.|Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, USA.|The Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, USA.
authors: Justin
authors: J
authors: Rendleman
authors: Perlmutter Cancer Center, New York University School of Medicine, New York, USA.|Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, USA.|The Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, USA.
authors: Esther
authors: E
authors: Kazlow
authors: Perlmutter Cancer Center, New York University School of Medicine, New York, USA.|Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, USA.|The Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, USA.
authors: Khagay
authors: K
authors: Nagdimov
authors: Perlmutter Cancer Center, New York University School of Medicine, New York, USA.|The Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, USA.|Department of Medicine, New York University School of Medicine, New York, USA.|Ronald O. Perelman, Department of Dermatology, New York University, New York, USA.
authors: Iman
authors: I
authors: Osman
authors: Department of Genetic and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA.
authors: Robert J
authors: RJ
authors: Klein
authors: Havener Eye Institute, Department of Ophthalmology and Visual Science, The Ohio State University, Columbus, OH USA.
authors: Frederick H
authors: FH
authors: Davidorf
authors: Havener Eye Institute, Department of Ophthalmology and Visual Science, The Ohio State University, Columbus, OH USA.
authors: Colleen M
authors: CM
authors: Cebulla
authors: Division of Human Genetics, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.|Havener Eye Institute, Department of Ophthalmology and Visual Science, The Ohio State University, Columbus, OH USA.
authors: Mohamed H
authors: MH
authors: Abdel-Rahman
authors: Perlmutter Cancer Center, New York University School of Medicine, New York, USA.|Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, USA.|The Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, USA.
authors: Tomas
authors: T
authors: Kirchhoff
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D010858:Pigmentation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014604:Uveal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor