Polygenic risk prediction models for colorectal cancer: A systematic review

Risk prediction models incorporating single nucleotide polymorphisms (SNPs) could lead to individualized prevention of colorectal cancer (CRC). However, the added value of incorporating SNPs into models with only traditional risk factors is still not clear. Hence, our primary aim was to summarize literature on risk prediction models including genetic variants for CRC, while our secondary aim was to evaluate the improvement of discriminatory accuracy when adding SNPs to a prediction model with only traditional risk factors.
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Polygenic risk prediction models for colorectal cancer: A systematic reviewSassanoetal. BMC Cancer (2022) 22:65https://doi.org/10.1186/s12885-021-09143-2 RESEARCH Open AccessPolygenic risk prediction modelsforcolorectal cancer: asystematic reviewMicheleSassano1†, MarcoMariani1†, GianluigiQuaranta1,2, RobertaPastorino2*and StefaniaBoccia1,2  Abstract  Background:  Risk prediction models incorporating single nucleotide polymorphisms (SNPs) could lead to individual- ized prevention of colorectal cancer (CRC). However, the added value of incorporating SNPs into models with only traditional risk factors is still not clear. Hence, our primary aim was to summarize literature on risk prediction models including genetic variants for CRC, while our secondary aim was to evaluate the improvement of discriminatory accu- racy when adding SNPs to a prediction model with only traditional risk factors. Methods:  We conducted a systematic review on prediction models incorporating multiple SNPs for CRC risk pre- diction. We tested whether a significant trend in the increase of Area Under Curve (AUC) according to the number of SNPs could be observed, and estimated the correlation between AUC improvement and number of SNPs. We estimated pooled AUC improvement for SNP-enhanced models compared with non-SNP-enhanced models using random effects meta-analysis, and conducted meta-regression to investigate the association of specific factors with AUC improvement. Results:  We included 33 studies, 78.79% using genetic risk scores to combine genetic data. We found no significant trend in AUC improvement according to the number of SNPs (p for trend = 0.774), and no correlation between the number of SNPs and AUC improvement (p = 0.695). Pooled AUC improvement was 0.040 (95% CI: 0.035, 0.045), and the number of cases in the study and the AUC of the starting model were inversely associated with AUC improvement obtained when adding SNPs to a prediction model. In addition, models constructed in Asian individuals achieved better AUC improvement with the incorporation of SNPs compared with those developed among individuals of European ancestry. Conclusions:  Though not conclusive, our results provide insights on factors influencing discriminatory accuracy of SNP-enhanced models. Genetic variants might be useful to inform stratified CRC screening in the future, but further research is needed. Keywords:  Colorectal cancer, Prediction models, Single nucleotide polymorphisms, Genetic risk score, Polygenic, Meta-analysis Introduction Colorectal cancer (CRC) is currently the third most com- monly diagnosed type of cancer and the second cause of cancer death worldwide, with an estimated 1.8 mil-*Correspondence: roberta.pastorino@unicatt.it lion new cases and 880 thousands deaths in 2018, with a†2 Michele Sassano and Marco Mariani contributed equally to this work. greater burden among males respect to females [1]. Typi- Department ofWoman andChild Health andPublic Health ‑ PublicHealth Area, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, cally, CRC can be considered a disease related to wealth.Italy National levels of both CRC incidence and mortalityFull list of author information is available at the end of the article are closely related to the income and development level © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted ...