Tovar-Parra David, Gutiérrez-Castañeda Luz Dary
General Dermatology Group, Hospital Universitario Centro Dermatologico Federico Lleras Acosta E.S.E, Bogotá 111511, Colombia.
Institut National de la Recherche Scientifique INRS, Centre Armand-Frappier Santé Biotechnologie, Laval, QC H7V 1B7, Canada.
Int J Mol Sci. 2025 May 14;26(10):4674. doi: 10.3390/ijms26104674.
Melanoma incidence is increasing, with distinct genetic and clinical patterns observed in the Latin American population. This study aimed to evaluate melanoma risk in a Colombian cohort through polygenic risk analysis using 37 variants across nine genes previously associated with melanoma. We performed polygenic risk score (PRS) analysis on 85 melanoma patients and 165 controls. Genotyping was performed for 37 melanoma-associated SNPs, and on the basis of previous GWAS reports, individual PRSs were calculated for each participant. The participants were then stratified into quartiles to examine risk gradients. In addition, phenotypic features such as eye and hair color were evaluated, and genetic models and haplotype analyses were performed, adjusting for sex and family history of cancer. PRS quartile stratification revealed a clear risk gradient. Notably, 31.8% of the melanoma cases were clustered in the highest-risk quartile (Q4), with a maximum PRS of 1.04. Variants in , , , and significantly contributed to risk, and light brown eye and hair colors were strongly associated with increased melanoma risk. Moreover, a protective haplotype in the region was identified among males. The integration of the PRS with clinical and phenotypic factors has potential for improving melanoma risk stratification in the Colombian population, warranting further investigation in larger, diverse cohorts.
黑色素瘤发病率正在上升，在拉丁美洲人群中观察到了独特的遗传和临床模式。本研究旨在通过对先前与黑色素瘤相关的9个基因中的37个变异进行多基因风险分析，评估哥伦比亚队列中的黑色素瘤风险。我们对85名黑色素瘤患者和165名对照进行了多基因风险评分（PRS）分析。对37个与黑色素瘤相关的单核苷酸多态性（SNP）进行基因分型，并根据先前的全基因组关联研究（GWAS）报告，为每个参与者计算个体PRS。然后将参与者分层为四分位数，以检查风险梯度。此外，评估了眼睛和头发颜色等表型特征，并进行了遗传模型和单倍型分析，对性别和癌症家族史进行了校正。PRS四分位数分层显示出明显的风险梯度。值得注意的是，31.8%的黑色素瘤病例聚集在最高风险四分位数（Q4）中，最大PRS为1.04。、、和中的变异对风险有显著贡献，浅棕色眼睛和头发颜色与黑色素瘤风险增加密切相关。此外，在男性中鉴定出了区域的一种保护性单倍型。将PRS与临床和表型因素相结合，有可能改善哥伦比亚人群中黑色素瘤的风险分层，值得在更大、更多样化的队列中进一步研究。
