Polygenic risk scores may improve colorectal cancer screening

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Despite the widespread adoption of screening programs in many high-income European countries, colorectal cancer rates remain high. Research from Finland, presented Monday at the annual conference of the European Society of Human Genetics, outlined how common genetic factors could be used to identify individuals at high risk of developing the disease, thus improving current colorectal screening strategies.

Most screening programs use a one-size-fits-all approach, in which people are screened beginning at a certain age and individual factors are not considered. The researchers hypothesized that developing a polygenic risk score (PRS) specifically for colorectal cancer might be a more effective approach. A PRS summarizes the combined impact of an individual’s genetic risk factors for a disease into a single score, allowing disease risk estimations and identifying those who might benefit from earlier screening.

The researchers embarked upon a large genomic study, using FinnGen study data — a collection of health and genome data from more than 400,000 Finnish individuals — from which they calculated a genome-wide PRS for colorectal cancer. While many prior PRS studies used smaller datasets not representative of the general population, this study used epidemiological and statistical approaches to calibrate estimates accordingly.

“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,” Dr. Max Tamlander of the University of Helsinki’s Institute for Molecular Medicine Finland, who presented the research, said in a statement.

Most colorectal cancer cases occur in individuals without a family history of the disease or other known risk factors. The researchers said the results 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 individuals who might benefit from more-frequent surveillance.

In Finland, general colorectal cancer screening starts at age 60; in other countries, at age 50. The researchers found that women and men in the top 1% of the PRS already had equivalent risks at ages 48.7 and 49.8, respectively. This indicated that individuals with a high PRS might benefit from earlier screening, and that a colorectal cancer-specific PRS based on an individual’s genetic risk may define more appropriate ages to begin screening.

As genotyping costs fall, PRS-based approaches may become more feasible for guiding population-wide screening. Millions of people already have their genomes available in large-scale biobanking initiatives, Tamlander noted, adding that, in addition, genetic data extracted from a single sample can be used over the course of a lifetime to calculate risk scores for many common diseases, including common cancers.

He said their findings are in line with other studies on PRSs in breast cancer, another common cancer with organized population-level screening.

Further clinical studies on cost-effectiveness and risk information communication are needed before colorectal PRSs can be widely implemented, the researchers noted.

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