Polygenic Risk Scores and Its Association With Cutaneous Melanoma Risk in the Swedish Population.

Polygenic risk scores can quantify an individual's genetic predisposition by combining the effects of multiple gene variants linked to melanoma susceptibility. Previous studies have demonstrated that PRS is strongly associated with melanoma risk and can improve the identification of high-risk individuals beyond that identified by traditional risk factors. The aim of this study was to calculate PRS for melanoma susceptibility in the Swedish population. Sixty-four single nucleotide polymorphisms, previously associated with melanoma susceptibility, were used to calculate PRS for 599 melanoma patients with or without family history of melanoma and 1180 controls. PRS values were significantly higher among melanoma patients than among controls, with an area under the receiver operating characteristic curve of 0.710. Individuals in the highest PRS decile had a fourfold increased melanoma risk compared with those in the 5th-6th decile. PRS was strongly influenced by the pigmentation-related traits skin phototype and hair color, as well as family history of melanoma and, to some extent, the number of primary melanoma tumors. The results show that PRS is strongly associated with melanoma risk in the Swedish population and may serve as a valuable tool for understanding genetic susceptibility and improving risk stratification in melanoma prevention and clinical management.