A polygenic risk score (PRS) is a method of predicting an individual’s genetic predisposition of developing diseases such as cancer over the next 10 years. Whether you’re a healthcare professional looking for better ways to screen individuals to understand their genetic predisposition to common cancers, or an individual wanting to understand their own personal genetic risk, one of the most common questions is: what happens if there is an increased polygenic risk score?
This article looks at the difference between polygenic risk score and more common forms of genetic testing and what the implications might be for those who have a higher risk score.
Genetic testing usually only looks for faults in what is known as the strong gene panels. Many diseases and certain types of cancer can be traced to variants in a single gene panel.
In breast cancer, for example, having a faulty BRCA gene greatly increases a woman’s chance of developing breast and ovarian cancer. However, complex diseases can occur as a result of multiple genomic variants, also known as the ‘weak’ genes and this is what polygenic risk scores assess.
“Poly” means many and “genic” involving genes. It looks at a much wider genetic panel and rather than looking for ‘faulty’ genes, it identifies patterns of behaviour amongst thousands of genes in order to measure the level of risk.
This comprehensive form of testing means that every single person tested gets to find out their personal level of risk, regardless of their family history or lifestyle, because it analyses the full weak gene panel.
Interpretation of a polygenic risk score
Once we have analysed an individual’s polygenic risk score, we report that individual’s risk of developing a specific cancer over the next ten years. We then compare that risk to the risk of the normal population of someone of their age. We report that as a ratio. If the ratio is above 1.00 then the individual tested is at higher risk than the normal population. If the ratio is below 1.00 then the individual tested is at lower risk than the normal population.
A higher risk score doesn’t mean that they will definitely develop the disease, but it does indicate an increased risk.
It is important to note, however, that even those with a high PRS may still not develop the disease. Diseases such as cancer involve both environmental and lifestyle elements as well as genetic, and therefore combining PRS with other established risk factors will help determine risk prediction.
Understanding the Antegenes test results report
Everything Genetic’s Antegenes polygenic risk score testing service comes with a personalised results report, along with full clinical guidance, that contains:
- Polygenic risk score: A score derived from thousands of genetic variants
- Personal risk: This shows an individual’s personal risk of developing for the cancer tested for over the next 10 years, compared to someone of your age in the general population.
- General population comparison: A number showing the average risk that someone similar has of developing the cancer tested for.
These numbers are then compared to give a ratio called Relative Risk. If the score is above 1, it means they are at higher risk of developing the cancer tested for.
Regular screening for those with increased risk
Depending on the type of cancer you are at risk of developing, those with a higher risk score will be recommended to speak to their GP or clinician about a regular screening programme. For example, breast cancer and prostate cancer, it is recommended to have annual screening from the age of 35 and 40 years respectively in the case of a higher PRS. For colorectal cancer, individuals should discuss a regular screening plan with their GP and for melanoma it is recommended to be referred to a special dermatological surveillance programme.
Polygenic risk scores hold significant promise in the age of large-scale genetic epidemiology to identify people who are at higher risk of developing cancer and other diseases. They are, therefore, beneficial for detecting cancer early when the disease is more easily treatable.
For more information about our Antegenes testing service, please contact partners@everythinggeneticltd.co.uk or speak to our sales team on +44 (0) 1270 623 179.
