Risk Factors

Genetic risk scores predict keratinocyte cancers: Queensland study


The genetic risk of keratinocyte cancers can be quantified by polygenic risk scores, which may supplement or eventually even replace the use of traditional environmental risk factors for targeting prevention and surveillance measures, findings from a long-running Queensland study suggest.

Researchers at the QIMR Berghofer Medical Research Institute, Brisbane, say that single nucleotide polymorphisms have little value in predicting the risk of BCC and SCC, but they postulated that an aggregation of common genetic variants for keratinocyte cancers (KC)could add value to currently used risk factors such as fair skin and UV exposure.

They therefore analysed data and genotyping of DNA samples from participants enrolled in the Nambour Skin Cancer Study since 1986 to investigate associations between KC risk and a polygenic risk score aggregation for 78 common genetic variants for KC.

When investigating PRS in 432 cases of KC and 566 non-KC controls they also divided the cohort into high risk (20%), intermediate risk (60%) and low risk (20%) groups.

Using logistic regression they found that a model including traditional risk factors (phenotypic and sun exposure-related), showed a significant 50% increase in odds of KC for every standard deviation of PRS (odds ratio (OR) =1.51).

Furthermore, for those in the top 20% high risk group,  PRS had over three times the risk of KC of those in the lowest risk group (OR=3.45). This group also had a higher absolute risk of KC per 100 person-years of 2.96 with PRS compared with 1.34 in the lowest risk group.

The researchers also noted that absolute risk was increased (AUC 0.72 to 0.74) on adding PRS to the prediction model, “confirming the value of PRS in enhancing the prediction of KC above traditional risk factors alone.”

While the absolute increase in predictive ability when adding the PRS was modest, the authors said it showed that using genetic risk scores could help further identify those at higher risk of skin cancer.

“Indeed in the future it may be more feasible to use the PRS to categorise risk for targeted screening at a population level, versus more intensive approaches such as assessing and recording traditional risk factors,” they wrote.

“PRS could be the basis of targeting those at the highest risk in the population for preventive measures, as well as for early detection [of KCs],” they suggested.

The findings are published in the Journal of European Academy of Dermatology and Venereology.

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