A risk score built from nearly 100 genetic variants commonly associated with colorectal cancer may help identify younger individuals who would benefit the most from preventive measures and early screening, according to research published in Gastroenterology.
Alexi N. Archambault, MPH, of the division of epidemiology at New York University School of Medicine, and colleagues wrote that there is a need for a new strategy to optimize CRC prevention among individuals younger than 50 years, among whom the incidence is on the rise.
“Weighing against the potential benefits of CRC early detection and prevention programs targeted to those aged younger than 50 years are concerns about adverse side effects and associated costs,” they wrote. “New approaches to disease prevention in younger adults are warranted, and assessing germline genetic variants, along with other known risk factors, could facilitate tailored early detection of high-risk individuals due to their genetic makeup and lifestyle.”
Using data from three large consortia that provided clinical and genotyping data, researchers developed a metric known as polygenic risk score (PRS), calculated based on single nucleotide polymorphisms associated with CRC. They studied the risk for CRC with a weighted PRS among 12,197 individuals younger than 50 years and compared them with 95,865 individuals aged at least 50 years.
Overall, Archambault and colleagues found associations with CRC per standard deviation of PRS for early-onset cancer were stronger than those found in later-onset cancer (P for interaction = .01). In the highest PRS quartile, the risk increased 3.7-fold for early-onset cancer (95% CI, 3.28-4.24) compared with a 2.9-fold increase in late-onset CRC (95% CI, 2.8-3.04).
The association was strongest among individuals without a first-degree family history of CRC. There was a 4.3-fold risk increased for early-onset CRC (95% CI, 3.61-5.01).
According to Archambault and colleagues, the risk score may help prioritize personalized screening regimens for individuals at increased susceptibility to early-onset CRC.
“Early-onset CRC is increasing in the U.S. and elsewhere,” they wrote. “By selecting high-risk individuals younger than 50 years of age, we can reduce the burden on early detection programs and potentially provide more individualized prevention approaches.” – by Alex Young
Disclosures: The authors report no relevant financial disclosures.