Using Polygenic Risk Scores to Stratify Patients Based on Risk of Invasive Cutaneous Melanoma

Polygenic risk scores (PRS) may serve as a viable tool to stratify patients based on their risk of invasive melanoma, according to a study published in JAMA Dermatology. 

“It is unknown whether germline genetic factors influence in situ melanoma risk differently than invasive melanoma risk,” the researchers noted.

In 3 genome-wide association meta-analyses, researchers analyzed 6 genome-wide significant loci associated with in situ melanoma and 18 loci associated with invasive melanoma using 4 population-based genetic cohorts: the UK Biobank, the FinnGen cohort, the QSkin Sun and Health Study, and the Queensland Study of Melanoma: Environmental and Genetic Associations (Q-MEGA). Data were collected from 1987 to 2022, and they were analyzed from September 2022 to June 2023.

The study uncovered a strong genetic correlation between the 2 classifications. Notably, the investigators observed loci near IRF4, KLF4, and HULC, which had notably larger effects for in situ melanoma compared with invasive melanoma, while MC1R had a significantly larger effect on invasive melanoma compared with in situ melanoma. Overall, the study showed that PRS, derived from comparing genetic risk of invasive melanoma with genetic risk of in situ melanoma, were significantly higher in participants with invasive melanoma.

“There is much shared genetic architecture between in situ melanoma and invasive melanoma. Despite indistinguishable heritability estimates between the melanoma classifications, PRS suggest germline genetics may influence whether a person gets in situ melanoma or invasive melanoma,” the researchers concluded. They added that “PRS could potentially help stratify populations based on invasive melanoma risk, informing future screening programs without exacerbating the current burden of melanoma overdiagnosis.”