Polygenic risk score across distinct colorectal cancer screening outcomes: from premalignant polyps to colorectal cancer

Abstract Background 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. However, few studies have previously assessed its usefulness in a fecal immunochemical test (FIT)-bas...

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Autores principales:	Mireia Obón-Santacana, Anna Díez-Villanueva, Maria Henar Alonso, Gemma Ibáñez-Sanz, Elisabet Guinó, Ana López, Lorena Rodríguez-Alonso, Alfredo Mata, Ana García-Rodríguez, Andrés García Palomo, Antonio J. Molina, Montse Garcia, Gemma Binefa, Vicente Martín, Victor Moreno
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Polygenic risk score Colorectal cancer Screening Positive fecal immunochemical test Positive predictive value Negative predictive value Medicine R
Acceso en línea:	https://doaj.org/article/733185c3c65f446a9006a4acf155d6ce
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spelling	oai:doaj.org-article:733185c3c65f446a9006a4acf155d6ce2021-11-14T12:17:06ZPolygenic risk score across distinct colorectal cancer screening outcomes: from premalignant polyps to colorectal cancer10.1186/s12916-021-02134-x1741-7015https://doaj.org/article/733185c3c65f446a9006a4acf155d6ce2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12916-021-02134-xhttps://doaj.org/toc/1741-7015Abstract Background 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. However, few studies have previously assessed its usefulness in a fecal immunochemical test (FIT)-based screening study. Methods A 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. Results The 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). Conclusions PRS 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.Mireia Obón-SantacanaAnna Díez-VillanuevaMaria Henar AlonsoGemma Ibáñez-SanzElisabet GuinóAna LópezLorena Rodríguez-AlonsoAlfredo MataAna García-RodríguezAndrés García PalomoAntonio J. MolinaMontse GarciaGemma BinefaVicente MartínVictor MorenoBMCarticlePolygenic risk scoreColorectal cancerScreeningPositive fecal immunochemical testPositive predictive valueNegative predictive valueMedicineRENBMC Medicine, Vol 19, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Polygenic risk score Colorectal cancer Screening Positive fecal immunochemical test Positive predictive value Negative predictive value Medicine R
spellingShingle	Polygenic risk score Colorectal cancer Screening Positive fecal immunochemical test Positive predictive value Negative predictive value Medicine R Mireia Obón-Santacana Anna Díez-Villanueva Maria Henar Alonso Gemma Ibáñez-Sanz Elisabet Guinó Ana López Lorena Rodríguez-Alonso Alfredo Mata Ana García-Rodríguez Andrés García Palomo Antonio J. Molina Montse Garcia Gemma Binefa Vicente Martín Victor Moreno Polygenic risk score across distinct colorectal cancer screening outcomes: from premalignant polyps to colorectal cancer
description	Abstract Background 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. However, few studies have previously assessed its usefulness in a fecal immunochemical test (FIT)-based screening study. Methods A 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. Results The 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). Conclusions PRS 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.
format	article
author	Mireia Obón-Santacana Anna Díez-Villanueva Maria Henar Alonso Gemma Ibáñez-Sanz Elisabet Guinó Ana López Lorena Rodríguez-Alonso Alfredo Mata Ana García-Rodríguez Andrés García Palomo Antonio J. Molina Montse Garcia Gemma Binefa Vicente Martín Victor Moreno
author_facet	Mireia Obón-Santacana Anna Díez-Villanueva Maria Henar Alonso Gemma Ibáñez-Sanz Elisabet Guinó Ana López Lorena Rodríguez-Alonso Alfredo Mata Ana García-Rodríguez Andrés García Palomo Antonio J. Molina Montse Garcia Gemma Binefa Vicente Martín Victor Moreno
author_sort	Mireia Obón-Santacana
title	Polygenic risk score across distinct colorectal cancer screening outcomes: from premalignant polyps to colorectal cancer
title_short	Polygenic risk score across distinct colorectal cancer screening outcomes: from premalignant polyps to colorectal cancer
title_full	Polygenic risk score across distinct colorectal cancer screening outcomes: from premalignant polyps to colorectal cancer
title_fullStr	Polygenic risk score across distinct colorectal cancer screening outcomes: from premalignant polyps to colorectal cancer
title_full_unstemmed	Polygenic risk score across distinct colorectal cancer screening outcomes: from premalignant polyps to colorectal cancer
title_sort	polygenic risk score across distinct colorectal cancer screening outcomes: from premalignant polyps to colorectal cancer
publisher	BMC
publishDate	2021
url	https://doaj.org/article/733185c3c65f446a9006a4acf155d6ce
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Polygenic risk score across distinct colorectal cancer screening outcomes: from premalignant polyps to colorectal cancer

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