葡萄膜黑色素瘤（UM）是一种罕见疾病，在皮肤白皙、眼睛浅色的人中发病率最高。眼睛颜色很大程度上由基因决定，并由一组单核苷酸多态性 (SNP) 定义。我们着手确定是否能够识别与预后相关的 SNP。我们对 392 名 UM 患者的外周血单核细胞进行 DNA 测序，获得了 6 个常见的与眼睛颜色相关的 SNP 的基因型。比较不同基因型患者的临床和组织病理学肿瘤特征、肿瘤染色体状态和患者生存率。在荷兰莱顿的莱顿大学医学中心，对 392 名接受 UM 摘除术的患者进行了比较。我们从外周血中分离出 DNA对 392 名 UM 患者的白细胞进行了测序，并使用 HIrisPlex-S 测定（Erasmus MC，Walsh 实验室）中的 6 个眼睛颜色 SNP 进行测序。从测序数据中提取的基因型上传到 HIrisPlexwebtool (https://hirisplex.erasmusmc.nl/) 用于眼睛颜色预测。我们使用 Pearson 卡方检验和 Mann-Whitney U 检验测试了眼睛颜色 SNP 与肿瘤特征和染色体畸变的关联，并使用 Kaplan-Meier 曲线、对数秩检验和 Cox 回归评估了生存率。葡萄膜黑色素瘤相关生存率在 392 名具有可分析基因型数据的患者中，307 名患者 (78%) 被分配为蓝眼睛，74 名患者 (19%) 被分配为棕色眼睛，11 名患者 (3%) 不能被分配为蓝色或棕色眼睛。遗传性蓝色眼睛的患者生存率较差 (P = 0.04)。这与 1 个基因型有关：具有编码蓝眼睛颜色的 rs12913832 (HERC2) G/G 基因型的患者预后较差 (P = 0.017)，且更常患有高风险肿瘤（3 号染色体单体；P = 0.04) 比具有 A/G 或 A/A 基因型的患者要高。rs12913832 (HERC2) 的 G/G 基因型与蓝眼睛颜色相关，不仅是与 UM 发生风险相关的遗传因素，但也与较差的预后有关，因为与高风险 UM 发展（携带 3 号染色体单体）的风险较高有关。作者对本文讨论的任何材料没有专有或商业利益。版权所有 © 2024 美国眼科学会。由爱思唯尔公司出版。保留所有权利。

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.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.Three hundred ninety-two patients who underwent enucleation for UM at the Leiden University Medical Center, Leiden, The Netherlands.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.Uveal melanoma-related survival.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.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).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.