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

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 scree...

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Autores principales: Obón-Santacana, Mireia, Díez-Villanueva, Anna, Alonso, Maria Henar, Ibáñez-Sanz, Gemma, Guinó, Elisabet, López, Ana, Rodríguez-Alonso, Lorena, Mata, Alfredo, García-Rodríguez, Ana, Palomo, Andrés García, Molina, Antonio J., Garcia, Montse, Binefa, Gemma, Martín, Vicente, Moreno, Victor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8574048/
https://www.ncbi.nlm.nih.gov/pubmed/34743725
http://dx.doi.org/10.1186/s12916-021-02134-x
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author Obón-Santacana, Mireia
Díez-Villanueva, Anna
Alonso, Maria Henar
Ibáñez-Sanz, Gemma
Guinó, Elisabet
López, Ana
Rodríguez-Alonso, Lorena
Mata, Alfredo
García-Rodríguez, Ana
Palomo, Andrés García
Molina, Antonio J.
Garcia, Montse
Binefa, Gemma
Martín, Vicente
Moreno, Victor
author_facet Obón-Santacana, Mireia
Díez-Villanueva, Anna
Alonso, Maria Henar
Ibáñez-Sanz, Gemma
Guinó, Elisabet
López, Ana
Rodríguez-Alonso, Lorena
Mata, Alfredo
García-Rodríguez, Ana
Palomo, Andrés García
Molina, Antonio J.
Garcia, Montse
Binefa, Gemma
Martín, Vicente
Moreno, Victor
author_sort Obón-Santacana, Mireia
collection PubMed
description 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 (OR(D10vsD1) 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-021-02134-x.
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spelling pubmed-85740482021-11-08 Polygenic risk score across distinct colorectal cancer screening outcomes: from premalignant polyps to colorectal cancer Obón-Santacana, Mireia Díez-Villanueva, Anna Alonso, Maria Henar Ibáñez-Sanz, Gemma Guinó, Elisabet López, Ana Rodríguez-Alonso, Lorena Mata, Alfredo García-Rodríguez, Ana Palomo, Andrés García Molina, Antonio J. Garcia, Montse Binefa, Gemma Martín, Vicente Moreno, Victor BMC Med Research Article 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 (OR(D10vsD1) 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-021-02134-x. BioMed Central 2021-11-08 /pmc/articles/PMC8574048/ /pubmed/34743725 http://dx.doi.org/10.1186/s12916-021-02134-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Obón-Santacana, Mireia
Díez-Villanueva, Anna
Alonso, Maria Henar
Ibáñez-Sanz, Gemma
Guinó, Elisabet
López, Ana
Rodríguez-Alonso, Lorena
Mata, Alfredo
García-Rodríguez, Ana
Palomo, Andrés García
Molina, Antonio J.
Garcia, Montse
Binefa, Gemma
Martín, Vicente
Moreno, Victor
Polygenic risk score across distinct colorectal cancer screening outcomes: from premalignant polyps to colorectal cancer
title 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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8574048/
https://www.ncbi.nlm.nih.gov/pubmed/34743725
http://dx.doi.org/10.1186/s12916-021-02134-x
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