TY - JOUR
T1 - Polygenic Risk Score for Defining Personalized Surveillance Intervals After Adenoma Detection and Removal at Colonoscopy
AU - Guo, Feng
AU - Edelmann, Dominic
AU - Cardoso, Rafael
AU - Chen, Xuechen
AU - Carr, Prudence R.
AU - Chang-Claude, Jenny
AU - Hoffmeister, Michael
AU - Brenner, Hermann
N1 - Funding Information:
Funding This work was supported by the German Research Council (BR 1704/6-1, BR1704/6-3, BR 1704/6-4, BR 1704/6-6, CH 117/1-1, and BR 1704/17-1); the German Federal Ministry of Education and Research, Germany (01KH0404, 01ER0814, 01ER0815, and 01GL1712); the National Cancer Institute, National Institutes of Health, US Department of Health and Human Services (R01 CA195789, U01 CA137088, and R01 CA059045); and by the German Cancer Aid, Germany (70113330). The funders played no role in the design of the study, the collection, analysis and interpretation of data, and in the decision to approve publication of the finished manuscript.
Publisher Copyright:
© 2022 AGA Institute
PY - 2022
Y1 - 2022
N2 - Background & Aims: Polygenic risk scores (PRSs) could help to define personalized colorectal cancer (CRC) screening strategies. The aim of this study was to evaluate whether a PRS, along with adenoma characteristics, could help to define more personalized and risk-adapted surveillance intervals. Methods: In a population-based, case-control study from Germany, detailed information on previous colonoscopies and a PRS based on 140 CRC-related, single-nucleotide polymorphisms was obtained from 4696 CRC cases and 3709 controls. Participants were classified as having low, medium, or high genetic risk according to tertiles of PRSs among controls. We calculated the absolute risk of CRC based on the PRS and colonoscopy history and findings. Results: We observed major variations of CRC risk according to the PRS, including among individuals with detection and removal of adenomas at colonoscopy. For instance, the estimated 10-year absolute risk of CRC for 50-year-old men and women with no polyps, for whom repeat screening colonoscopy is recommended after 10 years only, was 0.2%. Equivalent absolute risks were estimated for people with low-risk adenomas and low PRS. However, the same levels of absolute risk were reached within 3 to 5 years by those with low-risk adenomas and high PRS and with high-risk adenomas irrespective of the PRS. Conclusions: Consideration of genetic predisposition to CRC risk, as determined by a PRS, could help to define personalized, risk-adapted surveillance intervals after detection and removal of adenomas at screening colonoscopy. However, whether the risk variation is strong enough to direct clinical risk stratification needs to be explored further.
AB - Background & Aims: Polygenic risk scores (PRSs) could help to define personalized colorectal cancer (CRC) screening strategies. The aim of this study was to evaluate whether a PRS, along with adenoma characteristics, could help to define more personalized and risk-adapted surveillance intervals. Methods: In a population-based, case-control study from Germany, detailed information on previous colonoscopies and a PRS based on 140 CRC-related, single-nucleotide polymorphisms was obtained from 4696 CRC cases and 3709 controls. Participants were classified as having low, medium, or high genetic risk according to tertiles of PRSs among controls. We calculated the absolute risk of CRC based on the PRS and colonoscopy history and findings. Results: We observed major variations of CRC risk according to the PRS, including among individuals with detection and removal of adenomas at colonoscopy. For instance, the estimated 10-year absolute risk of CRC for 50-year-old men and women with no polyps, for whom repeat screening colonoscopy is recommended after 10 years only, was 0.2%. Equivalent absolute risks were estimated for people with low-risk adenomas and low PRS. However, the same levels of absolute risk were reached within 3 to 5 years by those with low-risk adenomas and high PRS and with high-risk adenomas irrespective of the PRS. Conclusions: Consideration of genetic predisposition to CRC risk, as determined by a PRS, could help to define personalized, risk-adapted surveillance intervals after detection and removal of adenomas at screening colonoscopy. However, whether the risk variation is strong enough to direct clinical risk stratification needs to be explored further.
KW - Adenoma
KW - Colonoscopy
KW - Colorectal Cancer
KW - Genetic Risk
KW - Surveillance
UR - http://www.scopus.com/inward/record.url?scp=85130350649&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2022.03.013
DO - 10.1016/j.cgh.2022.03.013
M3 - Article
C2 - 35331942
AN - SCOPUS:85130350649
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
SN - 1542-3565
ER -