Polygenic risk scores reveal missed opportunities in colorectal cancer screening in both European and non-European ancestry populations. — The Association Specialists
  1. Schedule
  2. Oral Presentations - Equity in cancer
  3. Polygenic risk scores reveal missed opportunities in colorectal cancer screening in both European and non-European ancestry populations.

Polygenic risk scores reveal missed opportunities in colorectal cancer screening in both European and non-European ancestry populations. (23961)

Mathias Seviiri 1 , Abishna Parasuraman 1 , Rawaa Eltayib 1 , Stuart MacGregor 1
  1. QIMR Berghofer Medical Research Institute, Herston, QLD, Australia

Background 

Colorectal cancer (CRC) screening reduces incidence and mortality, yet participation remains suboptimal and current criteria incompletely capture individual risk. Polygenic risk scores (PRS) may enable risk-stratified screening, but baseline screening rates among genetically high-risk individuals is poorly defined. We evaluated CRC screening uptake among genetically high-risk individuals across multiple population-based cohorts.

Methods:
We assessed CRC screening participation in CARTaGENE (Canada), UK Biobank (United Kingdom), and the All of Us Research Program (United States). A validated CRC PRS was applied to genotype data, with ancestry-adjusted percentiles used to define genetically high risk (top 20%). Screening uptake was evaluated according to country-specific guidelines, and multivariable logistic regression examined associations with ancestry and socioeconomic and health care access factors.

Results:
Among guideline-eligible individuals without a family history of CRC, screening participation was low; All of Us(15.9%), UK Biobank (30.9%), and CARTaGENE (35.9%). The screening rates were lower in participants of non-European ancestries E.g African (22.0%), East Asian (21.5%), and Hispanics (21.5%). Although eligible for screening, the majority of individuals with a high genetic risk (top 20% PRS), had never been unscreened for CRC; E.g 67.3% in CARTaGENE, and 74.1% in UKB among European ancestry. Screening rates were lower among genetically high risk non-European descent populations e.g 13% among Africans and 14% among South Asians. Non-European ancestry was associated with lower odds of screening e.g. in UK Biobank (OR = 0.70). Having a regular health care provider was strongly associated with higher screening participation.

Conclusions:
Under current screening strategies, most individuals at elevated genetic risk for CRC are not screened. Effective implementation of PRS-informed screening will require targeted interventions, particularly to address disparities related to ancestry and health care access.