Glasgow, UK: Colorectal cancer rates remain high despite widespread screening programs in many high-income European countries. Such programs tend to use a one-size-fits-all approach, where most people are screened at the same age and do not take individual factors into account when organizing population screening. Based on one of the largest genomics studies on the topic, Finnish researchers have described how common genetic factors can be used to identify individuals at high risk of developing the disease, thereby improving current colorectal screening strategies.
Max Tamlander, MD, of the Finnish Institute of Molecular Medicine (FIMM) at the University of Helsinki, will present his team’s work on the development of the polygenic risk score today (Monday, June 12) at the annual conference of the European Society of Human Genetics. (PRS), specifically for the treatment of colorectal cancer. The PRS summarizes the combined effect of a person’s genetic risk factors on disease into a single score. This makes it possible to assess an individual’s likely risk of disease and identify those who may benefit from earlier screening.
The researchers used data from the FinnGen study, a health and genomic dataset of more than 400,000 Finnish individuals, for which they calculated the genome-wide PRS for colorectal cancer. “The challenge with many previous PRS studies is that they were conducted in smaller data sets that are not representative of the general population, but in this study we used epidemiological and statistical methods to calibrate our estimates with this population,” explains Dr. Tamlander.
Most cases of colorectal cancer occur in individuals with no family history of the disease or other known strong risk factors. PVI offers a new way of assessing the risk of these individuals, which until now was based only on age. The researchers’ results also suggest that PRS may be useful for assessing future colorectal cancer risk after colonoscopy, the current gold standard screening method, and for identifying those individuals who would benefit from more frequent screening.
Currently, in Finland, colorectal cancer screening starts at age 60; in some other European countries, it starts earlier, at the age of 50. The researchers found that, based on the current Finnish screening age of 60, individuals with high PRS compared to low PRS could begin screening with a 16-year difference. For example, women and men in the 1% PVI already had equivalent risk at ages 48.7 and 49.8, respectively. “This suggests that colorectal cancer-specific PRS could identify a more appropriate age to start screening individuals based on their genetic risk,” says Dr. Tamlander.
As the cost of genotyping continues to decrease, PRS-based methods may become a viable way to target population-wide screening. “Millions of individuals already have their genomes available for large-scale biobanking initiatives,” says Dr. Tamlander. “For example, the FinnGen biobank study already contains the genomic data of more than 7% of all Finns and will soon increase to around 10%. One very useful aspect of PVI is that genetic data from a single sample can be used over a lifetime to calculate risk scores for many common diseases, including the most common cancers.
Further clinical trials, as well as data on cost-effectiveness and effective communication of risk information, are needed before large-scale colorectal PRS can be implemented, the researchers say. Another problem is that, until now, PVIs have been developed mainly for people of European descent, so they may not be valid for people of other ancestries.
“However, our findings are in good agreement with other studies on PRS in breast cancer, another common cancer, with organized population screening. Large clinical trials in breast cancer are currently underway to evaluate the results of personalized breast cancer screening, and the results will inform the implications of genome-based, risk-based screening for colon cancer and other diseases. , continues Dr. Tamlander.
“In the future, risk-based approaches that consider genetic factors along with other important risk factors may help guide how we can most effectively screen for colorectal cancer,” concludes Dr. Tamlander.
Professor Alexandre Reymond, chair of the conference, said: “If our health systems are to truly embrace personal health in the future, it is essential to recognize those at risk.”