Genetic markers of pigmentation identify genomic sites of possible uveal melanoma risk
Roughly 2,500 people in the United States are diagnosed annually with uveal melanoma (UM), a rare form of melanoma that arises in the iris, ciliary body or choroid layer of the eye.
Clinical data suggest that uveal melanoma is more common in Caucasians and individuals with light eye coloration, but the genetic mechanisms underlying the development of the malignancy are largely unknown.
A recent study co-led by an OSUCCC – James researcher provides insight into the cause of UM. The study found the first evidence of a link between genes associated with eye color and development of the malignancy. Leading the study were ophthalmologic pathologist and cancer geneticist Mohamed Abdel-Rahman, MD, PhD, of the OSUCCC – James, and cancer geneticist Tomas Kirchhoff, PhD, of the Perlmutter Cancer Center of NYU School of Medicine.
“This important paper will help focus future UM research efforts on the interactions of certain pigmentary genes with other genetic and environmental risk factors,” Abdel-Rahman says.
“This could provide a paradigm shift in the field. Our study suggests that in eye melanoma a difference in pigmentation may play a direct cancer-driving role, unrelated to sunlight protection,” he adds. Progress in understanding the genetic risk factors in the development of uveal melanoma has been limited, the researchers say, because this cancer is rare and large sample populations are unavailable.
To overcome that limitation, Abdel-Rahman, Kirchhoff and their colleagues focused on 28 single-nucleotide polymorphisms (SNPs) that are associated with increased risk of cutaneous melanoma and looked for links to uveal melanoma.
The researchers analyzed samples from 272 UM patients and 1,782 controls, most of whom were treated at Ohio State. They identified five variants that were significantly associated with UM. The three most important of these mapped to a region on chromosome 15 that determines eye color.
The researchers believe the findings provide a deeper understanding of both ocular and cutaneous melanoma.
Published in the journal Scientific Reports.