Eye Color Could Predispose Patients to Uveal Melanoma

Genes related to eye color may cause cancer of the eye.

Findings from a recent study suggest a relationship between eye color and a rare form of uveal melanoma.

Uveal melanoma, or eye melanoma, is very rare, and only 2500 people are diagnosed with this form of cancer in the United States annually. It has been known to typically affect Caucasians with light colored eyes.

In a study published by Scientific Reports, researchers discovered that uveal melanoma is caused by 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. This could provide a paradigm shift in the field,” said co-author Abdel-Rahman, MD, PhD. “Our study suggests that in eye melanoma the pigmentation difference may play a direct cancer-driving role, not related to sunlight protection.”

The researchers said that there has been limited progress in understanding the genetic risk factors involved with uveal melanoma, since there is a lack of genetic data due to the rarity of the disease. They analyzed samples from more than 270 patients with uveal melanoma to determine whether there are common genetic factors between uveal melanoma and skin melanoma, according to the study.

Researchers analyzed 29 inherited mutations linked to skin melanoma to determine whether there was an associated risk. They discovered that 5 of the mutations were associated with uveal melanoma risk, and 3 of those mutations occurred in the genetic region that determines eye color, according to the study.

“Genetic susceptibility to uveal melanoma has been traditionally thought to be restricted only to a small groups of patients with family history. Now our strong data shows the presence of novel genetic risk factors associated with this disease in a general population of uveal melanoma patients,” said co-author Tomas Kirchhoff, PhD. “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 in the deeper molecular understanding of both diseases.”

Researchers believe their findings will create large national and international systematic analyses of germline genome data in these patients.

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