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

Autor: Sullivan BA; Cooperative Studies Program Epidemiology Center-Durham, Durham VA Health Care System, Durham, North Carolina.; Division of Gastroenterology, Duke University, Durham, North Carolina., Qin X; Cooperative Studies Program Epidemiology Center-Durham, Durham VA Health Care System, Durham, North Carolina.; Division of Gastroenterology, Duke University, Durham, North Carolina., Redding TS 4th; Cooperative Studies Program Epidemiology Center-Durham, Durham VA Health Care System, Durham, North Carolina., Weiss D; Cooperative Studies Program Coordinating Center, Perry Point VA Medical Center, Perry Point, Maryland., Upchurch J; Cooperative Studies Program Epidemiology Center-Durham, Durham VA Health Care System, Durham, North Carolina., Sims KJ; Cooperative Studies Program Epidemiology Center-Durham, Durham VA Health Care System, Durham, North Carolina., Dominitz JA; Division of Gastroenterology, VA Puget Sound Health Care System, Seattle, Washington.; Division of Gastroenterology, University of Washington School of Medicine, Seattle, Washington., Stone A; Cooperative Studies Program Pharmacogenomics Analysis Laboratory, Central Arkansas Veterans Health System, Little Rock, Arkansas., Ear B; Cooperative Studies Program Epidemiology Center-Durham, Durham VA Health Care System, Durham, North Carolina., Williams CD; Cooperative Studies Program Epidemiology Center-Durham, Durham VA Health Care System, Durham, North Carolina.; Division of Gastroenterology, Duke University, Durham, North Carolina., Lieberman DA; Division of Gastroenterology, VA Portland Health Care System, Portland, Oregon.; Division of Gastroenterology, Oregon Health & Science University, Portland, Oregon., Hauser ER; Cooperative Studies Program Epidemiology Center-Durham, Durham VA Health Care System, Durham, North Carolina.; Division of Gastroenterology, Duke University, Durham, North Carolina.
Jazyk: angličtina
Zdroj: Gastro hep advances [Gastro Hep Adv] 2023 Oct 10; Vol. 3 (2), pp. 151-161. Date of Electronic Publication: 2023 Oct 10 (Print Publication: 2024).
DOI: 10.1016/j.gastha.2023.10.001
Abstrakt: Background and Aims: Colorectal cancer (CRC) polygenic risk scores (PRS) may help personalize CRC prevention strategies. We investigated whether an existing PRS was associated with advanced neoplasia (AN) in a population undergoing screening and follow-up colonoscopy.
Methods: We evaluated 10-year outcomes in the Cooperative Studies Program #380 screening colonoscopy cohort, which includes a biorepository of selected individuals with baseline AN (defined as CRC or adenoma ≥10 mm or villous histology, or high-grade dysplasia) and matched individuals without AN. A PRS was constructed from 136 prespecified CRC-risk single nucleotide polymorphisms. Multivariate logistic regression was used to evaluate the PRS for associations with AN prevalence at baseline screening colonoscopy or incident AN in participants with at least one follow-up colonoscopy.
Results: The PRS was associated with AN risk at baseline screening colonoscopy ( P  = .004). Participants in the lowest PRS quintile had more than a 70% decreased risk of AN at baseline (odds ratio 0.29, 95% confidence interval 0.14-0.58; P < .001) compared to participants with a PRS in the middle quintile. Using a PRS cut-off of more than the first quintile to indicate need for colonoscopy as primary screening, the sensitivity for detecting AN at baseline is 91.8%. We did not observe a relationship between the PRS and incident AN during follow-up ( P  = .28).
Conclusion: A PRS could identify individuals at low risk for prevalent AN. Ongoing work will determine whether this PRS can identify a subset of individuals at sufficiently low risk who could safely delay or be reassured about noninvasive screening. Otherwise, more research is needed to augment these genetic tools to predict incident AN during long-term follow-up.
Databáze: MEDLINE
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