Send to

Choose Destination
Br J Dermatol. 2019 Mar 25. doi: 10.1111/bjd.17917. [Epub ahead of print]

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

Author information

Department of Dermatology, Massachusetts General Hospital, Boston, MA, U.S.A.
Department of Population Medicine, Harvard Pilgrim Healthcare Institute, Boston, MA, U.S.A.
Department of Cancer Biology and Genetics, Comprehensive Cancer Center, Ohio State University, 998 Biomedical Research Tower, 460 W 12th Ave, Columbus, OH, 43210, U.S.A.



Genome-wide association studies (GWAS) have identified thousands of susceptibility variants, although 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 two-to-threefold increases in risk and modest improvements in risk prediction (2-7% increases). PRS are associated with twofold and threefold 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.


Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center