Maria Chiara Gelmi, Laurien E Houtzagers, Annemijn P A Wierenga, Mieke Versluis, Bastiaan T Heijmans, Gregorius P M Luyten, Peter de Knijff, Marije Te Raa, Rick H de Leeuw, Martine J Jager
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引用次数: 0
Abstract
Purpose: Uveal melanoma (UM) is a rare disease, with the highest incidence in people with a fair skin and light eyes. Eye colour is largely genetically determined and defined by a set of single nucleotide polymorphisms (SNPs). We set out to determine whether we could identify a SNP that is related to prognosis.
Design: We sequenced DNA from peripheral blood mononuclear cells of 392 patients with UM and obtained the genotype of six common eye colour-related SNPs. Clinical and histopathologic tumour characteristics, tumour chromosome status, and patient survival were compared among patients with different genotypes.
Subjects: 392 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 six eye colour SNPs from the HIrisPlex-S assay. The genotypes extracted from the sequencing data were uploaded onto the Hirisplex webtool (https://hirisplex.erasmusmc.nl/) for eye colour prediction. We tested the association of eye colour SNPs with tumour characteristics and chromosome aberrations using Pearson's chi-square test and Mann-Whitney U test and survival with Kaplan-Meier curves with log-rank test and Cox regression.
Main outcome measures: UM-related survival.
Results: Of the total cohort of 392 patients with analysable genotype data, 307 (78%) were assigned to have blue eyes, 74 (19%) brown eyes and 11 (3%) could not be assigned to either blue or brown. Patients with a genetically-blue eye colour had a worse survival (p = 0.04). This was related to one genotype: patients with the G/G genotype of rs12913832 (HERC2) which codes for blue eye colour had a worse prognosis (p = 0.017), which was related to more often having high-risk tumours (monosomy of chromosome 3, p = 0.04) than patients with an A/G or A/A genotype.
Conclusion: The G/G genotype of rs12913832 (HERC2), which is related to blue eye colour, is not only a genetic factor related to the risk to develop a UM, but is also linked to a worse prognosis, due to an association with a higher risk of developing a high-risk UM (carrying monosomy of chromosome 3).
期刊介绍:
The journal Ophthalmology, from the American Academy of Ophthalmology, contributes to society by publishing research in clinical and basic science related to vision.It upholds excellence through unbiased peer-review, fostering innovation, promoting discovery, and encouraging lifelong learning.