Model identifies 24-year difference in recommended CRC screening age between men, women
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Key takeaways:
- Men had a 1.6-fold increased risk for colorectal cancer occurrence and reached equivalent risk 6 years earlier than women.
- Those in the highest polygenic risk score decile had double the risk for occurrence.
A risk-advancement period approach using sex and polygenic risk score helped identify starting ages for colorectal cancer screening, with men reaching an equivalent risk for CRC occurrence and mortality at a younger age than women.
“Colorectal cancer risk varies widely, even in the population at ‘average risk’ or without a family history, but there are no established routines for translating this variation into personalized starting ages of screening,” Hermann Brenner, MD, MPH, professor and head of the division of clinical epidemiology and again research at the German Cancer Research Center, told Healio.
Seeking to define risk-adapted starting ages for screening based on the concept of risk advancement period (RAP), using sex and polygenic risk score (PRS) as risk indicators, Brenner and colleagues evaluated data from 242,779 participants (median age, 55 years; 55.7% women) in the UK Biobank with no previous bowel cancer screening or family history of CRC.
Researchers based PRS on 139 of 140 previously identified CRC-related risk variants and calculated each participant’s score by quantifying the number of risk alleles of each respective variant. The median PRS was 134 risk alleles at baseline.
During a median follow-up of 11.2 years, there were 2,714 incident cases of CRC and at 12.8 years, there were 758 deaths. Men had a 1.6-fold increased risk for CRC occurrence (HR = 1.57; 95% CI, 1.46-1.7) and reached the equivalent risk for CRC approximately 6 years (RAP = 5.6; 95% CI, 4.6-6.6) earlier than women.
“The PRS was strongly related to CRC risk in a dose-response manner,” Brenner and colleagues wrote in JAMA Network Open.
Further, individuals in the lowest PRS deciles had half the risk (HR = 0.51; 95% CI, 0.41-0.62) and reached equivalent levels of risk at 8 years older age (RAP = –8.4; 95% CI, –11 to –5.9) compared with those in the middle decile. Those in the highest decile had double the risk (HR = 2.29; 95% CI, 2.01-2.62) and reached equivalent levels of risk at 10 years younger age (RAP = 10.3; 95% CI, 8.5-12.1). Researchers observed similar associations between CRC mortality and corresponding RAPs.
Using CRC mortality as a benchmark, risk-adapted starting ages for screening ranged from 50 to 67 years for women and 45 to 62 years for men, researchers wrote.
“We showed that, among people with no family history of colorectal cancer, risk-adapted starting ages of colorectal cancer screening would vary by as much as 24 years between men with a high genetic risk score, who should start screening earlier, and women with a low genetic risk score, who might consider starting later,” Brenner told Healio. “Our analytical approach and our results may help to translate results of epidemiological studies on colorectal cancer risk in personalized screening recommendations.”
Brenner continued: “Research is needed on further refinement and implementation of risk-adapted recommendations on starting ages of colorectal cancer screening in routine practice.”
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