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Background: Keratinocyte cancer (KC) risk is determined by genetic and environmental factors. Genetic risk can be quantified by polygenic risk scores (PRS), which sum the combined effects of single nucleotide polymorphisms (SNPs)., Objectives: Our objective here was to evaluate the contribution of the summed genetic score to predict the KC risk in the phenotypically well-characterized Nambour population., Methods: We used PLINK v1.90 to calculate PRS for 432 cases, 566 controls, using 78 genome-wide independent SNPs that are associated with KC risk. We assessed the association between PRS and KC using logistic regression, stratifying the cohort into three risk groups (high 20%, intermediate 60%, low 20%)., Results: The fully adjusted model including traditional risk factors (phenotypic and sun exposure-related), showed a significant 50% increase in odds of KC per standard deviation of PRS (odds ratio (OR) = 1.51; 95% confidence interval (CI) = 1.30-1.76, P = 5.75 × 10 -8 ). Those in the top 20% PRS had over three times the risk of KC of those in the lowest 20% (OR = 3.45; 95% CI = 2.18-5.50, P = 1.5 × 10 -7 ) and higher absolute risk of KC per 100 person-years of 2.96 compared with 1.34. Area under the ROC curve increased from 0.72 to 0.74 on adding PRS to the fully adjusted model., Conclusions: These results show that PRS can enhance the prediction of KC above traditional risk factors., (© 2022 European Academy of Dermatology and Venereology.)