Genome-wide association studies and polygenic risk scores for skin cancer: clinically useful yet?

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Genome-wide association studies (GWAS) have identified thousands of susceptibility variants, though most have been associated with small individual risk estimates that offer little predictive value. However, combining multiple variants into polygenic risk scores (PRS) may be more informative. Multiple studies have developed PRS composed of GWAS-identified variants for cutaneous cancers. This review highlights data from these studies.


To review published GWAS and PRS studies for melanoma, cutaneous squamous cell carcinoma (cSCC), and basal cell carcinoma (BCC), and discuss their potential clinical utility.


We searched PubMed and the National Human Genome Research Institute-European Bioinformatics Institute GWAS catalogue to identify relevant studies.


Results from 21 GWAS (11 melanoma, 3 cSCC, 7 BCC) and 11 PRS studies are summarized. Six loci in pigmentation genes overlap between these three cancers (ASIP/RALY, IRF4, MC1R, OCA2, SLC45A2, and TYR). Additional loci overlap for cSCC/BCC and BCC/melanoma, but no other loci are shared between cSCC and melanoma. PRS for melanoma show roughly 2-to-3-fold increases in risk and modest improvements in risk prediction (2-7% increases). PRS are associated with 2-fold and 3-fold increases in risk of cSCC and BCC, respectively, with small improvements (2% increase) in predictive ability.


Existing data indicate that PRS may offer small, but potentially meaningful, improvements to risk prediction. Additional research is needed to clarify the potential utility of PRS in cutaneous carcinomas. Clinical translation will require well-powered validation studies incorporating known risk factors to evaluate PRS as tools for screening. This article is protected by copyright. All rights reserved.

Br. J. Dermatol.
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Genome-wide association studies and polygenic risk scores for skin cancer: clinically useful yet?
Roberts MR, Asgari MM, Toland AE