Use of Polygenic Risk Scores to Select Screening Intervals After Negative Findings From Colonoscopy

Abstract

BACKGROUND & AIMS: Polygenic risk scores (PRSs) could help to define starting ages for colorectal cancer (CRC) screening. However, the role of PRS in determining the length of screening interval after negative findings from colonoscopies is unclear. We aimed to evaluate CRC risk according to PRS and time since last negative colonoscopy. METHODS: We collected data from 3827 cases and 2641 CRC-free controls in a population-based casecontrol study in Germany. We constructed a polygenic risk scoring system, based on 90 singlenucleotide polymorphisms, associated with risk of CRC in people of European descent. Participants were classified as having low, medium, or high genetic risk according to tertiles of PRSs among controls. Multiple logistic regression models were used to assess CRC risk according to PRS and time since last negative colonoscopy. RESULTS: Compared to individuals without colonoscopy in the low PRS category, a 42%-85% lower risk of CRC was observed for individuals who had a negative finding from colonoscopy within 10 years. Beyond 10 years after a negative finding from colonoscopy, significantly lower risk only persisted for the low and medium PRS groups, but not for the high PRS group. Adjusted odds ratios were 0.44 (95% CI, 0.29-0.68), 0.51 (95% CI, 0.34-0.77), and 0.85 (95% CI, 0.58-1.23) in the low, medium, and high PRS group, respectively. Within any time interval, risks were lower for distal than for proximal CRCs. CONCLUSIONS: Based on findings from a population-based case-control study, the recommended 10-year screening interval for colonoscopy may not need to be shortened among people with high PRSs, but could potentially be prolonged for people with low and medium PRSs. Studies are needed to address personalized time intervals for repeat colonoscopies in average-risk screening cohorts.

Polygenic Risk Score for Defining Personalized Surveillance Intervals After Adenoma Detection and Removal at Colonoscopy

“…Previous studies have shown that PRS-based assessment of genetic risk has the potential to identify low-and high-risk populations and might help guide personalized recommendations on starting age for CRC screening and time intervals between repeat screening colonoscopies. [8][9][10] Focusing screening colonoscopy on those at highest risk may enable offering screening colonoscopy in countries with limited resources, and riskadapted screening might make screening colonoscopy even more cost effective or cost saving in countries with sufficient colonoscopy capacities. Besides risk-adapted definition of starting ages of screening and time intervals between repeat screening colonoscopies, riskadapted definitions of surveillance intervals after detection and removal of adenomas might further enhance the most efficient use of colonoscopy resources and reduce the possibility of overusing surveillance colonoscopy among people with low risk and underusing among people with high risk, which are major issues in clinical practice.…”

“…7 We calculated a weighted PRS by summing the product of the reported regression coefficients and number of risk alleles (0, 1, and 2) across the 140 SNPs for all study participants. In line with previous studies, [8][9][10] participants were categorized further into 3 groups (low, medium, or high PRS) according to tertiles of the PRS among controls.…”

“…8,9 A recent study from our group showed that a PRS based on 90 SNPs also may have the potential to define a personalized length of rescreening intervals after a negative colonoscopy. 10 This study suggested, for instance, that the commonly recommended 10-year screening interval for colonoscopy may not need to be shortened among people with high PRS but potentially could be prolonged for people with low and medium PRSs.…”

Preferences for a polygenic test to estimate cancer risk in a general Australian population

“…4 When applied to cancer screening, it may impact the age at which someone commences screening, screening intervals, and the type of test used. [5][6][7] Focusing screening on those most at risk may be more cost-effective and avoid the potential sequelae of false positives and overdiagnosis for individuals who fall into lower-risk categories. 8,9 Clinical trials are actively investigating how PRS guided screening compares with conventional screening for breast and colorectal cancer.…”

Polymorphisms within Autophagy-Related Genes Influence the Risk of Developing Colorectal Cancer: A Meta-Analysis of Four Large Cohorts

“…703/2010, the "Ethikkommission Burgenland", KRAGES, 33/2010; and the Institute of Experimental Medicine in Prague, Czech Republic). Information about these four populations has been described in detail elsewhere [3,[19][20][21][22].…”