Pellegrini Stefania, Potjer Thomas P, Del Bianco Paola, Vecchiato Antonella, Fabozzi Alessio, Piccin Luisa, Tonello Debora, van der Stoep Nienke, Tinsley Emily, Landi Maria Teresa, Iles Mark M, Menin Chiara
Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy.
Department of Clinical Genetics, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands.
Biology (Basel). 2024 Nov 20;13(11):954. doi: 10.3390/biology13110954.
Recent genome-wide association studies (GWASs) have identified many single nucleotide polymorphisms (SNPs) that alone weakly affect melanoma risk, but their combined effect on a polygenic risk score (PRS) can have a far bigger impact on estimating risk. However, the PRS is not yet at the stage of being utilized in clinical practice, and further evidence is needed. In this study, 270 melanoma patients fulfilling the criteria for a suspected genetic predisposition but with a negative genetic test for high/medium-penetrance genes were genotyped for 57 SNPs selected in previous GWASs to construct a PRS model. We found a significantly higher mean PRS in all melanoma cases than in controls (0.58 vs. 0.00, < 0.001), and the mean PRS in multiple primary melanoma cases was twice that in single melanoma cases (0.689 vs. 0.362, = 0.025). Interestingly, our results confirm the association of the PRS not only with other melanoma risk factors but also with a younger age at diagnosis. This evidence supports the potentially powerful discriminative role of PRS in the selection of high-risk patients who should undergo stricter surveillance protocols.
近期的全基因组关联研究（GWAS）已经鉴定出许多单核苷酸多态性（SNP），这些单核苷酸多态性单独对黑色素瘤风险的影响较弱，但其对多基因风险评分（PRS）的综合影响在估计风险方面可能产生大得多的影响。然而，PRS尚未达到可应用于临床实践的阶段，还需要更多证据。在本研究中，对270例符合疑似遗传易感性标准但高/中穿透性基因检测为阴性的黑色素瘤患者，针对先前GWAS中选择的57个SNP进行基因分型，以构建PRS模型。我们发现，所有黑色素瘤病例的平均PRS显著高于对照组（0.58对0.00，<0.001），多原发性黑色素瘤病例的平均PRS是单发性黑色素瘤病例的两倍（0.689对0.362，=0.025）。有趣的是，我们的结果证实PRS不仅与其他黑色素瘤风险因素相关，还与诊断时较年轻的年龄相关。这一证据支持了PRS在选择应接受更严格监测方案的高危患者方面可能具有的强大鉴别作用。
