Photo Credit: Michael Lutz
The following is a summary of “Survival in uveal melanoma patients is linked to genetic variation at HERC2 SNP rs12913832,” published in the September 2024 issue of Ophthalmology by Gelmi et al.
Uveal melanoma (UM) is an elevated incidence in individuals with fair skin and light eyes, primarily genetically confined by single nucleotide polymorphisms (SNPs).
Researchers conducted a retrospective study to specify if an SNP associated with eye color could be identified as a prognostic factor for UM.
They sequenced DNA from peripheral blood mononuclear cells of 392 patients with UM, genotyped 6 common eye color-related SNPs, and compared clinical and histopathologic tumor characteristics, tumor chromosome status, and patient survival among different genotypes. The genotypes extracted from the sequencing data were uploaded onto the Hirisplex web tool (https://hirisplex.erasmusmc.nl/) for eye color prediction and tested the association of eye color SNPs with tumor 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.
The results showed that of the 392 patients with analyzable genotype data, 307 (78%) were assigned to have blue eyes, 74 (19%) had brown eyes, and 11 (3%) could not be transferred. Patients with genetically blue eyes had worse survival (P= 0.04). This was related to the G/G genotype of rs12913832 (HERC2), which codes for blue eye color and had a worse prognosis (P= 0.017)and having high-risk tumors (monosomy of chromosome 3, P= 0.04) than patients with an A/G or A/A genotype.
They concluded that HERC2, associated with blue eye color, is not only a genetic factor related to the risk of developing 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).
Source: aaojournal.org/article/S0161-6420(24)00540-2/abstract
