Illustration showing colorectal cancer
Credit: Mohammed Haneefa Nizamudeen/Getty Images

Researchers from the Institute for Molecular Medicine Finland (FIMM) have demonstrated that a colorectal cancer (CRC) polygenic risk score (PRS) they have developed has the potential to inform the timing of when patients should begin screening for the disease. Use of the PRS could help address the fact that despite widespread adoption of screening methods, the incidence of CRC in European populations remains high.

For their research, presented this week at the European Society of Human Genetics, the investigators, led by Max Tamlander, MD, of FIMMS, used data from the FinnGen study that has gathered both health and genome data from more than 400,000 people in Finland, which they used to calculate a genome-wide PRS.

“A challenge of many prior PRS studies is that they have been performed in smaller datasets that are not representative of the general population, but in this study we used epidemiological and statistical approaches to calibrate our estimates with that population,” Tamlander said.

While most European countries starts when a patient turns 50, in Finland most first screenings aren’t done until a person turns 60. Based on that screening age, the new research found that those Finnish people with a high PRS compared with those with a low PRS could have first screening as much as 16 years apart. As an example, the team said that women and men in the top 1% of the PRS had equivalent risks at ages 48.7 and 49.8 respectively. According to Talmander, having using this PRS for colorectal cancer can be used to more appropriately suggest the right ages different people should begin screening, due to their genetic risk of developing the disease.

The researchers suggest that as the cost of genotyping continues to decrease, taking a PRS-based approach to determine disease risk could be an effective method of customizing screening ages of patients within a population. Further, as more and more countries undertake their own population-based genomic biobanking efforts, a significant portion of people may already have their genomic data available that could be used to determine their PRS.

“The FinnGen biobank study already contains the genomic data of over 7% of all Finns, and this will soon increase to around 10%. One very useful aspect of PRSs is that genetic data extracted from a single sample can be used over the course of life to calculate risk scores for many common diseases, including the most common cancers,” Talmander noted.

There still remain hurdles to bringing the colorectal cancer polygenic risk score into broad clinical practice, however. First, cost-effectiveness studies must be conducted to determine real-world utility of PRS, as well as developing methods of properly communicating the risk information derived from these methods. Also of concern is the fact that most PRS have been developed using genomic data that has been primarily from people of European descent, and may not be applicable to people of different ancestries.

“Our findings are well in line with other studies on PRSs in breast cancer,” Tamlander said. “For breast cancer, large clinical trials are currently underway to evaluate the performance of personalized breast cancer screening, and their results will help us to understand the implications of genome-guided, risk-based screening for colorectal cancer, as well as other diseases.

“In the future, risk-based approaches considering genetic factors alongside other relevant risk factors have potential for personalizing recommendations regarding how we could most effectively screen for colorectal cancer.”

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