Iris Colour and the Risk of Developing Uveal Melanoma.

Uveal melanoma (UM) is a global disease which especially occurs in elderly people. Its incidence varies widely between populations, with the highest incidence among Caucasians, and a South-to-North increase in Europe. As northern Europeans often have blond hair and light eyes, we wondered whether iris colour may be a predisposing factor for UM and if so, why. We compared the distribution of iris colour between Dutch UM patients and healthy Dutch controls, using data from the Rotterdam Study (RS), and reviewed the literature regarding iris colour. We describe molecular mechanisms that might explain the observed associations. When comparing a group of Dutch UM patients with controls, we observed that individuals from Caucasian ancestry with a green/hazel iris colour (Odds Ratio (OR) = 3.64, 95% Confidence Interval (CI) 2.57-5.14) and individuals with a blue/grey iris colour (OR = 1.38, 95% CI 1.04-1.82) had a significantly higher crude risk of UM than those with brown eyes. According to the literature, this may be due to a difference in the function of pheomelanin (associated with a light iris colour) and eumelanin (associated with a brown iris colour). The combination of light-induced stress and aging may affect pheomelanin-carrying melanocytes in a different way than eumelanin-carrying melanocytes, increasing the risk of developing a malignancy.

Evaluation of Racial, Ethnic, and Socioeconomic Associations With Treatment and Survival in Uveal Melanoma, 2004-2014.

Importance: Identifying disparities in uveal melanoma (UM) treatment patterns and survival across racial, ethnic, and socioeconomic (SES) groups reveals possible inequities in ophthalmologic health care. Objective: To examine the association of race, ethnicity, and SES with UM treatment and survival. Design, Setting, and Participants: A retrospective cohort analysis of 28% of the US population using the Surveillance, Epidemiology, and End Results (SEER) 18 registries from January 1, 2004, to December 31, 2014, was conducted. Data analysis was performed from April to July 2018. SEER identified 4475 individuals using International Classification of Diseases for Oncology, Third Edition site and morphology codes. Exposures: Race, ethnicity, and SES estimated by tertile using Yost Index composite scores. Main Outcomes and Measures: Treatment odds ratios (ORs), 1-year and 5-year survival estimates, mortality hazard ratios (HRs), and Kaplan-Meier survival curves. Hypothesis was formulated before data collection. Results: Multivariate analyses of 4475 individuals (2315 [51.7%] men; non-Hispanic white, 4130 [92.3%]; nonwhite, 345 [7.7%]) showed that patients who were nonwhite (OR, 1.45; 95% CI, 1.12-1.88) and socioeconomically disadvantaged (lower SES: OR, 2.21; 95% CI, 1.82-2.68; middle SES: OR, 1.86; 95% CI, 1.56-2.21) were more likely to receive primary enucleation. No interactions were observed between race/ethnicity, SES, and stage at diagnosis. From 2004 to 2014, rates of primary enucleation decreased across all racial/ethnic and SES groups, but disparities persisted. Socioeconomically disadvantaged patients had lower 5-year all-cause survival rates (lower SES: 69.2%; middle SES: 68.1%; and upper SES: 73.8%), although disease-specific survival did not vary significantly by racial/ethnic or SES strata. Mortality risk was associated with older age at diagnosis (56-68 years: HR, 1.70; 95% CI, 1.44-2.01; ≥69 years: HR, 3.32; 95% CI, 2.85-3.86), advanced stage of UM (stage 2: HR, 1.40; 95% CI, 1.19-1.65; stage 3: HR, 2.26; 95% CI, 1.87-2.73; and stage 4: HR, 10.09; 95% CI, 7.39-13.77), and treatment with primary enucleation (HR, 2.14; 95% CI, 1.88-2.44) with no racial/ethnic or SES variation. Conclusions and Relevance: In this study, SEER data from 2004 to 2014 suggest that nonwhite and socioeconomically disadvantaged patients with UM are more likely to be treated with primary enucleation, although no such variation appears to exist in disease-specific survival. These differences reveal opportunities to address issues regarding treatment choice in UM.

Prognosis of uveal melanoma based on race in 8100 patients: The 2015 Doyne Lecture.

A retrospective, nonrandomized, interventional case series of 8100 patients with uveal melanoma were evaluated for melanoma-related metastasis based on patient race. The patient race was Caucasian (n=7918, 98%), Hispanic (n=105, 1%), Asian (n=44, <1%), or African American (n=33, <1%). On the basis of race (Caucasian, Hispanic, Asian, and African American), significant differences were noted in mean age at presentation (58, 48, 44, and 52 years; P<0.001), distance of posterior tumor margin to foveola (5, 5, 6, and 4 mm; P<0.001), distance of posterior tumor margin to optic disc (5, 5, 6, and 4 mm) (P<0.001), tumor base (11, 12, 12, and 13 mm; P<0.001), tumor thickness (5.4, 7.1, 6.5, and 7.5 mm; P<0.001), intraocular hemorrhage (10, 14, 11, and 24%; P=0.02), and rupture of Bruch's membrane (20, 27, 39, and 36%; P=0.001). On the basis of multivariate analysis, the rate of metastasis increased with increasing age (P<0.001), ciliary body location (P<0.001), increasing tumor base (P<0.001), increasing tumor thickness (P<0.001), pigmented tumor (P=0.001), subretinal fluid (P=0.001), intraocular hemorrhage (P=0.045), and extraocular extension (P=0.036). Kaplan-Meier estimates of metastasis at 3, 5, and 10 were 8, 15, and 25% in Caucasians; 13, 13, and 13% in Hispanics; 4, 4, and 36% in Asians; and 8, 8, and 8% in African Americans. Compared with Caucasians, despite relative risk for metastasis of 0.31 for African Americans, 0.73 for Hispanics, and 1.42 for Asians, there was no statistical difference in metastasis, or death from uveal melanoma based on race. In summary, uveal melanoma showed similar prognosis for all races.

One's location of residence as an important factor related to the occurrence of multiple primary cancer among patients with uveal melanoma.

PURPOSE: This study has attempted to analyze the impact of where one lives related to the incidence of multiple primary cancer among patients with uveal melanoma. MATERIAL AND METHODS: The group that was studied consisted of 240 patients. They were separated from other patients who had been diagnosed and treated with uveal melanoma at the Department of Ophthalmology and Ocular Oncology at Jagiellonian University Medical College in the period between January 1998 to December 2007. Ninety seven patients, diagnosed with another primary cancer, was defined as a test group. The remaining 143 patients constituted the control group. RESULTS: In the test group individuals were mostly residents of large cities, most often with population of more than 500 thousand inhabitants. The control group represented residents of small towns, each having less than 10000 persons population. CONCLUSIONS: The findings of this study are pointing to the dependence of the detectability of multiple primary cancer among patients with uveal melanoma on the availability of modern diagnostic methods. uveal melanoma, multiple primary cancer.

Clinical and cytogenetic characteristics of choroidal melanoma in Vietnamese Asians.

PURPOSE: To report the clinical and cytogenetic characteristics of choroidal melanoma in Vietnamese Asians. METHODS: In three Vietnamese Asians with choroidal melanoma, transscleral fine needle aspiration biopsy (FNAB) was performed immediately before iodine-125 brachytherapy. Biopsy was examined for cytopathology, fluorescence in situ hybridization (FISH) for the centromere of chromosome 3, and analyzed by 250K whole genome Mapping Array and U133 plus 2.0 Expression Array. RESULTS: Three Vietnamese Asian men (50, 59, and 30 years of age) with clinical diagnosis of choroidal melanoma and no evidence of metastasis had FNAB immediately before Iodine-125 brachytherapy. Cytopathology showed heavily pigmented cells suggestive of or consistent with melanoma. Mapping Array and Expression Array revealed cytogenetic aberrations and gene expression profiles characteristic of choroidal melanoma. One patient (Case 2) with chromosome 3 loss and chromosome 8q gain developed biopsy-proven liver metastasis three years after brachytherapy. One patient (Case 1) with chromosome 6p, 9q and 17q gain and a second patient (Case 3) with 6p, 8q and 9q gains and losses in 6q and 8p have had no evidence of metastasis three years after brachytherapy. CONCLUSIONS: In this series of Vietnamese Asians with heavily pigmented choroidal melanoma, the clinical characteristics, cytogenetic aberrations and gene expression profiles were similar to characteristics in other ethnic/racial groups and the cytogenetic aberration of chromosome 3 loss was associated with the development of liver metastasis.

Population-based incidence of conjunctival melanoma in various races and ethnic groups and comparison with other melanomas.

PURPOSE: To investigate racial and ethnic differences in the incidence of conjunctival melanoma in a large population-based study. DESIGN: Observational cross-sectional study. METHODS: Using data from 1992 through 2003 provided by the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program, we calculated age-adjusted incidence rates of conjunctival melanoma in various racial and ethnic groups (Black, American Indian, Asian and Pacific Islander, Hispanic, and non-Hispanic White). In addition, we calculated the standard incidence ratios (risk ratios) and 95% confidence intervals to describe the differences within these racial and ethnic groups. RESULTS: From 1992 through 2003, there were a total of 168 conjunctival melanomas diagnosed in 13 SEER registries with known racial and ethnic groups. The annual age-adjusted incidence rates (per million population) of conjunctival melanoma was 0.18 (Blacks), 0.17 (American Indians), 0.15 (Asians), 0.33 (Hispanics), and 0.49 (non-Hispanic Whites). The difference in the incidence of conjunctival melanoma between Whites and Blacks or Asians was statistically significant, but was not significant between Blacks and Asians. CONCLUSIONS: The overall White-to-Black incidence ratio in conjunctival melanoma was 2.6:1, which is much less than that of uveal melanoma (18:1) and cutaneous melanoma (13:1 to 26:1), but is similar to that of mucosal melanoma (2.2:1 to 2.3:1). The cause and significance of this difference of racial and ethnic incidence in various melanomas are discussed.

Population-based incidence of uveal melanoma in various races and ethnic groups.

PURPOSE: To investigate racial/ethnic differences in the development of uveal malignant melanoma in a large population-based study. DESIGN: Observational cross-sectional study. METHODS: With the 1992 to 2000 data that was provided by the National Cancer Institute's Surveillance, Epidemiology, and End Results Program, we calculated age-adjusted incidence rates of uveal melanoma in various racial/ethnic groups (black, Asian and Pacific Islander, Hispanic, and non-Hispanic white). In addition, we calculated the standard incidence ratio (risk ratio) and 95% confidence interval to describe the differences within these racial/ethnic groups. RESULTS: From 1992 to 2000, there were a total of 1352 uveal melanomas that were diagnosed in 11 Surveillance, Epidemiology, and End Results registries with known racial/ethnic groups. The annual age-adjusted incidence (per million population) of uveal melanoma was 0.31 (black), 0.38 (Asian), 1.67 (Hispanic), and 6.02 (non-Hispanic white). The difference in the incidence of uveal melanoma between each racial/ethnic group was highly statistically significant, with the exception of the black versus the Asian population in which there was no statistically significant difference. CONCLUSION: The relative risk of uveal melanoma was 1.2 for Asian and Pacific Islander patients, 5.4 for Hispanic patients, and 19.2 for non-Hispanic white patients as compared with the black patients. If the non-Hispanic white population and the Hispanic population were combined, then the overall white:black ratio was 18:1.

Cutaneous, ocular and visceral melanoma in African Americans and Caucasians.

The incidence and age-specific rates of cutaneous, ocular and visceral melanoma were compared in blacks, whites and other ethnic groups using data obtained from the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute for the years 1973-2001. As the SEER Program is now more mature and includes a larger proportion of minority populations, we thought it important to revisit these observations in more detail. Overall, the rate of cutaneous melanoma was higher in white males but, prior to 50 years of age, the rate was higher in white females. Compared with white males, white females and black males and females had proportionally higher rates of melanoma on the lower extremities. Cutaneous and ocular melanomas were, as expected, more common in whites than in blacks or in other groups. The age-specific rates for ocular and cutaneous melanoma were similar for blacks and other ethnic groups, but differed from those of whites. Patients with a previous diagnosis of cutaneous melanoma had a significantly higher probability of developing ocular melanoma than the general population. Age-specific rates were similar in all three groups for visceral melanoma. In all three racial/ethnic groups, age-specific rate patterns were different between cutaneous, ocular and visceral melanoma, suggesting a different pathogenesis. Visceral melanoma develops later in life, after the age of 60 years, compared with cutaneous or ocular melanomas.

Clinical features of uveal metastases in Korean patients.

PURPOSE: To report clinical features of uveal metastatic tumors in Korean patients who have different cancer profiles than those of patients in Western countries. METHODS: The authors performed a retrospective chart review on all patients with evaluated uveal metastases. RESULTS: Fourteen patients were diagnosed. One eye involved the iris, and 14 eyes of 13 patients involved the choroid. The metastases came from a primary cancer of the breast in four (29%), the lung in four (29%), the stomach in two (14%), the esophagus in one (7%), the common bile duct in one (7%), the kidney in one (7%), and unknown in one (7%). Thirteen (93%) of 14 choroidal metastases were associated with subretinal fluid, and eight (57%) eyes had tumors that were posterior to the equator. At the time of diagnosis, all patients had a history of cancer, and 11 patients had a metastatic lesion elsewhere. Three patients were undergoing chemotherapy. All three cases from gastric or esophageal cancer had a thicker choroidal mass and massive exudative retinal detachment. CONCLUSIONS: The authors' series of uveal metastases showed a higher incidence from gastrointestinal cancer in Korean patients. Choroidal tumors from gastric or esophageal cancer seemed to be larger with massive exudation.

Incidence of surgically treated uveal melanoma by race and ethnicity.

OBJECTIVE: The purpose of the study was to determine the race- and ethnicity-specific incidence of histologically confirmed uveal melanoma. DESIGN: The study design was a retrospective study of histologically confirmed cases of primary uveal melanoma submitted to the Florida Cancer Data System (FCDS). MAIN OUTCOME MEASURES: Race-, gender-, and Hispanic-specific incidence rates of uveal melanoma were measured. Calculations are based on Florida census data and Hispanic population estimates from the University of Florida Bureau of Economic and Business Research. RESULTS: From 1981 through 1993, 873 histologically confirmed uveal melanomas were reported to the FCDS. Four melanomas occurred in black non-Hispanics, 47 in white Hispanics, and none in black Hispanics. The relative risk of uveal melanoma for blacks compared to non-Hispanic whites was 0.03 (95% confidence interval, 0.01-0.08). Non-Hispanic white men had 72 times the risk of uveal melanoma compared to black men; non-Hispanic white women experienced a 22-fold risk compared to black women. White Hispanics were less likely to develop uveal melanoma than white non-Hispanics (relative risk, 0.36; 95% confidence interval, 0.27-0.48). CONCLUSION: The risk of uveal melanoma in blacks is exceptionally low. The reason for lower risk of uveal melanoma in white Hispanics than in white non-Hispanics is not known but could be related to the protective effects associated with dark skin pigmentation or may be because of unknown cultural-environmental exposures or socioeconomic factors.

Uveal melanomas in black patients: a case series and comparative review.

Uveal melanomas are rare in black patients. Of a total of 2586 patients with the diagnosis of posterior uveal melanoma who were managed in the Oncology Service at Wills Eye Hospital from 1974 to 1987, 10 patients (0.39%) were black. Data on patient age (mean: 53.9 years), sex (male-to-female ratio: 7:3), and relative frequency of disease between black (0.39% of total cases) and white patients were similar to that of previous reports. The distinguishing characteristics (incidence, risk factors, complications, and prognostic indicators) of uveal melanoma in black versus white patients also were reviewed.

Ciliary body malignant melanoma in a black child.

Uveal malignant melanoma is uncommon both in children and in black patients. There has been only one previous report of this type of tumor occurring in a black child. This paper presents the case history of a 5-year-old black girl who presented with a mass arising from the ciliary body and choroid. This was found to be a malignant melanoma on histological examination. The difficulties in diagnosis are discussed and the histological features presented.

Diffuse malignant change in a ciliochoroidal melanocytoma in a patient of mixed racial background.

A 69-year-old man of mixed racial background was discovered to have a large, deeply pigmented mass in his left eye with a history of rapid growth during the previous 6 months. The eye was enucleated, and histopathological examination revealed an epithelioid malignant melanoma arising from a melanocytoma.