Colorectal Cancer Polygenic Risk Score Is Associated With Screening Colonoscopy Findings but Not Follow-Up Outcomes

Area of Science:

• Genetics and Genomics
• Gastroenterology
• Cancer Prevention

Background:

• Personalized prevention strategies for colorectal cancer (CRC) may utilize polygenic risk scores (PRS).
• Existing PRS utility for identifying individuals with advanced neoplasia (AN) requires validation in screening populations.

Purpose of the Study:

• To assess the association between a CRC PRS and prevalent AN at baseline colonoscopy.
• To evaluate the PRS's ability to predict incident AN during long-term follow-up.

Main Methods:

• Utilized data from the Cooperative Studies Program #380 screening colonoscopy cohort.
• Constructed a PRS from 136 CRC-risk single nucleotide polymorphisms.
• Employed multivariate logistic regression to analyze PRS association with AN prevalence and incidence.

Main Results:

• The PRS was significantly associated with AN risk at baseline screening (P = .004).
• Individuals in the lowest PRS quintile showed a >70% decreased risk of prevalent AN (OR 0.29, P < .001).
• The PRS demonstrated 91.8% sensitivity for detecting baseline AN when used as a screening indicator; no association with incident AN was found during follow-up (P = .28).

Conclusions:

• A PRS can identify individuals at low risk for prevalent advanced neoplasia.
• Further investigation is needed to determine if this PRS can safely guide screening intervals or non-invasive screening recommendations.
• Augmenting genetic tools is necessary for predicting incident AN in long-term follow-up.