Survival in Patients with Uveal Melanoma Is Linked to Genetic Variation at HERC2 Single Nucleotide Polymorphism rs12913832.

Autor:	Gelmi MC; Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands., Houtzagers LE; Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands., Wierenga APA; Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands., Versluis M; Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands., Heijmans BT; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands., Luyten GPM; Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands., de Knijff P; Forensic Laboratory for DNA Research, Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands., Te Raa M; Forensic Laboratory for DNA Research, Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands., de Leeuw RH; Forensic Laboratory for DNA Research, Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands., Jager MJ; Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: m.j.jager@lumc.nl.
Jazyk:	angličtina
Zdroj:	Ophthalmology [Ophthalmology] 2024 Sep 07. Date of Electronic Publication: 2024 Sep 07.
DOI:	10.1016/j.ophtha.2024.09.001
Abstrakt:	Purpose: Uveal melanoma (UM) is a rare disease, with the highest incidence in people with fair skin and light eyes. Eye color is largely genetically determined and is defined by a set of single nucleotide polymorphisms (SNPs). We set out to determine whether we could identify a SNP related to prognosis. Design: We sequenced DNA from peripheral blood mononuclear cells of 392 patients with UM and obtained the genotype of 6 common eye color-related SNPs. Clinical and histopathologic tumor characteristics, tumor chromosome status, and patient survival were compared among patients with different genotypes. Participants: Three hundred ninety-two patients who underwent enucleation for UM at the Leiden University Medical Center, Leiden, The Netherlands. Methods: We isolated DNA from peripheral blood leukocytes of 392 patients with UM and performed sequencing, using 6 eye color SNPs from the HIrisPlex-S assay (Erasmus MC, Walsh lab). The genotypes extracted from the sequencing data were uploaded onto the HIrisPlexwebtool (https://hirisplex.erasmusmc.nl/) for eye color prediction. We tested the association of eye color SNPs with tumor characteristics and chromosome aberrations using Pearson's chi-square test and the Mann-Whitney U test and evaluated survival with Kaplan-Meier curves with the log-rank test and Cox regression. Main Outcome Measures: Uveal melanoma-related survival. Results: Of 392 patients with analyzable genotype data, 307 patients (78%) were assigned blue eyes, 74 patients (19%) were assigned brown eyes, and 11 patients (3%) could not be assigned to either blue or brown. Patients with a genetically blue eye color showed worse survival (P = 0.04). This was related to 1 genotype: patients with the G/G genotype of rs12913832 (HERC2), which codes for blue eye color showed a worse prognosis (P = 0.017) and more often had high-risk tumors (monosomy of chromosome 3; P = 0.04) than in patients with an A/G or A/A genotype. Conclusions: The G/G genotype of rs12913832 (HERC2), which is related to blue eye color, not only is a genetic factor related to the risk of UM develop, but also is linked to a worse prognosis because of an association with a higher risk of a high-risk UM developing (carrying monosomy of chromosome 3). Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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