A new study identified that the genetic mechanisms behind a rare form of eye melanoma are also associated with genetic risk for skin melanoma. [Rocky89/Getty Images]
A new study identified that the genetic mechanisms behind a rare form of eye melanoma are also associated with genetic risk for skin melanoma. [Rocky89/Getty Images]

Clinical and epidemiological data have always pointed to eye cancer being more common among those individuals with light eye coloration and fair skin—however, the genetic mechanisms underlying disease development have been largely unknown. Now new research from investigators at The Ohio State University (OSU) and New York University (NYU) sheds light on specific inherited genetic differences for an increased risk of uveal melanoma, a rare cancer that arises from the pigment cells that determine eye color.    

“This is a very important discovery that will guide future research efforts to explore the interactions of these pigmentary genes with other genetic and environmental risk factors in cancers not linked to sun exposure, such as eye melanoma,” explained co-senior study author Mohamed Abdel-Rahman, M.D., Ph.D., ophthalmologic pathologist and cancer geneticist at OSU Comprehensive Cancer Center. “This could provide a paradigm shift in the field. Our study suggests that in eye melanoma the pigmentation difference may play a direct cancer-driving role not related to sunlight protection.”

Close to 2500 people are diagnosed with uveal melanoma in the United States annually. Unlike other solid tumors, there has been limited progress in understanding the contribution of genetic risk factors to the development of uveal melanoma. Many researchers suggest that this is primarily due to the absence of comprehensive genetic data from patients because large sample cohorts for this rare cancer type have not been available for research.

To overcome these limitations, researchers analyzed samples from more than 270 patients with uveal melanoma. Because there is a known clinical connection between eye melanoma and skin cancer, the researchers sought to determine whether there were commonly shared genetic factors between both diseases—analogous to the inherited genetic risk for skin melanoma, which has been more extensively explored in the previous medical literature.

The findings from this study were published recently in Scientific Reports in an article entitled “Genetic Markers of Pigmentation Are Novel Risk Loci for Uveal Melanoma.”

The research team analyzed 29 inherited genetic mutations previously linked with skin melanoma to determine if there was an associated risk of uveal melanoma. Interestingly, the analysis uncovered that five genetic mutations were significantly associated with uveal melanoma risk. Moreover, the three most significant genetic associations occurred in a genetic region that determines eye color.

“Genetic susceptibility to uveal melanoma has been traditionally thought to be restricted only to small groups of patients with family history,” noted co-senior study author Tomas Kirchoff, Ph.D., assistant professor at the Perlmutter Cancer Center of NYU School of Medicine. “Now our strong data shows the presence of novel genetic risk factors associated with this disease in a general population of uveal melanoma patients. But this data is also important because it indicates—for the first time—that there is a shared genetic susceptibility to both skin and uveal melanoma mediated by genetic determination of eye color. This knowledge may have direct implications for the deeper molecular understanding of both diseases.”

The investigators are optimistic that their findings will fuel the formation of large national and international research consortiums to conduct comprehensive, systematic analysis of inherited (germline) genome data in large cohorts of uveal melanoma patients. 

“This type of collaboration is critically needed to dissect additional modifying genetic risk factors that may be uveal melanoma specific,” Dr. Kirchhoff remarked. “This has significant consequences not only for the prevention or early diagnosis of the disease but potentially for more improved therapies for at-risk patients.”

Dr. Abdel-Rahman added that “federal funding will be crucial to support research of rare cancers such as eye melanoma as it is likely, as shown in this study, that the impact of such research will extend across the different cancer types.”

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