Abstract
BackgroundDifferent risk-based colorectal cancer (CRC) screening strategies, such as the use of polygenic risk scores (PRS), have been evaluated to improve effectiveness of these programs. However, few studies have previously assessed its usefulness in a fecal immunochemical test (FIT)-based screening study.MethodsA PRS of 133 single nucleotide polymorphisms was assessed for 3619 participants: population controls, screening controls, low-risk lesions (LRL), intermediate-risk (IRL), high-risk (HRL), CRC screening program cases, and clinically diagnosed CRC cases. The PRS was compared between the subset of cases (n = 648; IRL+HRL+CRC) and controls (n = 956; controls+LRL) recruited within a FIT-based screening program. Positive predictive values (PPV), negative predictive values (NPV), and the area under the receiver operating characteristic curve (aROC) were estimated using cross-validation.ResultsThe overall PRS range was 110–156. PRS values increased along the CRC tumorigenesis pathway (Mann-Kendall P value 0.007). Within the screening subset, the PRS ranged 110-151 and was associated with higher risk-lesions and CRC risk (ORD10vsD1 1.92, 95% CI 1.22–3.03). The cross-validated aROC of the PRS for cases and controls was 0.56 (95% CI 0.53–0.59). Discrimination was equal when restricted to positive FIT (aROC 0.56), but lower among negative FIT (aROC 0.55). The overall PPV among positive FIT was 0.48. PPV were dependent on the number of risk alleles for positive FIT (PPVp10-p90 0.48–0.57).ConclusionsPRS plays an important role along the CRC tumorigenesis pathway; however, in practice, its utility to stratify the general population or as a second test after a FIT positive result is still doubtful. Currently, PRS is not able to safely stratify the general population since the improvement on PPV values is scarce.
Highlights
Different risk-based colorectal cancer (CRC) screening strategies, such as the use of polygenic risk scores (PRS), have been evaluated to improve effectiveness of these programs
Participants were classified into 7 groups according to their status: 1008 population controls, 670 screening controls, 286 low-risk lesions (LRL), 352 intermediate-risk lesions (IRL), 226 high-risk lesions (HRL), 70 screening CRC, and 1007 clinically diagnosed CRC (937 from Cancer Genetics & Genomics (CRCGEN) and 70 from COLSCREEN)
The mean PRS values increased along the CRC tumorigenesis pathway (Mann-Kendall P value 0.007): from 131.7 to 134.5 for population controls and clinically diagnosed CRC, respectively
Summary
Different risk-based colorectal cancer (CRC) screening strategies, such as the use of polygenic risk scores (PRS), have been evaluated to improve effectiveness of these programs. Few studies have previously assessed its usefulness in a fecal immunochemical test (FIT)-based screening study. Screening strategies reduce the incidence and mortality of CRC by detecting premalignant polyps and cancers at an earlier stage. Compared to no CRC screening, all screening modalities (i.e., fecal occult blood test (FOBT), endoscopy screening, computed tomographic colonography, stool DNA test) provide additional years of life at a cost that is deemed acceptable by most industrialized nations [2]. Among FOBT, the fecal immunochemical test (FIT) is often preferred as it does not require dietary restrictions before sample collection and has higher sensitivity and a lower incidence of interval CRC after a negative screening result [4]. The target population for CRC screening is aged between 50 to 69 years, uses the FIT, and reached participation rates of 45.3% in 2016 with a slow increasing trend [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
