Polygenic Risk Scoring May Help Optimize Colorectal Cancer Screening

Researchers have identified how common genetic factors can be used to discern which individuals are at high risk for developing colorectal cancer using a polygenic risk score (PRS). The results were presented today at the annual conference of the European Society of Human Genetics.

To conduct this study, researchers led by Max Tamlander, MD, used data from the FinnGen study, a collated of health and genome data from more than 400,000 Finnish individuals, to calculated a genome-wide PRS for colorectal cancer. “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,” said Dr. Tamlander.

Most cases of colorectal cancer occur in individuals who do not have a family history of the disease or any other known strong risk factors. PRSs offer a new way of assessing risk in these individuals, which until now has been based on attained age alone. The researchers’ results also show that a PRS could be useful in the assessment of future colorectal cancer risk after a colonoscopy, the current gold-standard screening method, and identify those individuals who would potentially benefit from more frequent surveillance.

In Finland, screening for colorectal cancer in the general population currently starts at age 60; in some other European countries it starts earlier, from 50. The researchers found that, based on the current screening age 60 in Finland, individuals with a high PRS as compared to those with a low PRS could start screening at up to 16 years apart. For example, women and men at the top 1% of the PRS already had equivalent risks at ages 48.7 and 49.8, respectively. “This indicates that a colorectal cancer-specific PRS would be able to define more appropriate ages to start screening for individuals based on their genetic risk,” says Dr Tamlander.

The majority of CRC cases occur in individuals with no family history or known risk factors for the disease. PRSs offer a new way of assessing risk in these individuals, which until now has been based on attained age alone, the researchers noted. The findings show that a PRS could be useful in the assessment of future colorectal cancer risk following a colonoscopy

In Finland, CRC screening in the general population begins at 60; in some other European countries it starts earlier, from 50. However, based on these findings, individuals with a high PRS as compared to those with a low PRS could start screening at up to 16 years apart. For example, the investigators noted, women and men at the top 1% of the PRS already had equivalent risks at ages 48.7 and 49.8, respectively. “This indicates that a colorectal cancer-specific PRS would be able to define more appropriate ages to start screening for individuals based on their genetic risk,” says Dr Tamlander.

Further clinical studies and data are needed prior to the large-scale use of the colorectal PRS, say the researchers. “However, our findings are well in line with other studies on PRSs in breast cancer, another common cancer with organised population-level screening. For breast cancer, large clinical trials are currently underway to evaluate the performance of personalised 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.”, Dr Tamlander added.