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

BMC Medicine

Montse Garcia¹  Gemma Binefa¹  Vicente Martín²  Alfredo Mata³  Ana García-Rodríguez⁴  Lorena Rodríguez-Alonso⁵  Andrés García Palomo⁶  Antonio J. Molina⁷  Ana López⁸  Elisabet Guinó⁸  Mireia Obón-Santacana⁸  Anna Díez-Villanueva⁸  Maria Henar Alonso⁸  Victor Moreno⁹  Gemma Ibáñez-Sanz^1,10 

[1] Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029, Madrid, Spain;Cancer Screening Unit, Cancer Prevention and Control Program, Catalan Institute of Oncology, L’Hospitalet de Llobregat, Barcelona, Spain;Early Detection of Cancer Research Group, EPIBELL Program, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain;Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029, Madrid, Spain;The Research Group in Gene - Environment and Health Interactions (GIIGAS)/Institut of Biomedicine (IBIOMED), Universidad de León, 24071, León, Spain;Faculty of Health Sciences, Department of Biomedical Sciences, Area of Preventive Medicine and Public Health, Universidad de León, 24071, León, Spain;Digestive System Service, Moisés Broggi Hospital, Sant Joan Despí, Spain;Endoscopy Unit, Digestive System Service, Viladecans Hospital-IDIBELL, Viladecans, Spain;Gastroenterology Department, Bellvitge University Hospital, L’Hospitalet de Llobregat, Spain;Servicio de Oncología, Complejo Asistencial Universitario de León, 24071, León, Spain;The Research Group in Gene - Environment and Health Interactions (GIIGAS)/Institut of Biomedicine (IBIOMED), Universidad de León, 24071, León, Spain;Faculty of Health Sciences, Department of Biomedical Sciences, Area of Preventive Medicine and Public Health, Universidad de León, 24071, León, Spain;Unit of Biomarkers and Suceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L’Hospitalet del Llobregat, 08908, Barcelona, Spain;ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908, Barcelona, Spain;Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029, Madrid, Spain;Unit of Biomarkers and Suceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L’Hospitalet del Llobregat, 08908, Barcelona, Spain;ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908, Barcelona, Spain;Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029, Madrid, Spain;Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, 08007, Barcelona, Spain;Unit of Biomarkers and Suceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L’Hospitalet del Llobregat, 08908, Barcelona, Spain;ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908, Barcelona, Spain;Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029, Madrid, Spain;Gastroenterology Department, Bellvitge University Hospital, L’Hospitalet de Llobregat, Spain;

关键词: Polygenic risk score;    Colorectal cancer;    Screening;    Positive fecal immunochemical test;    Positive predictive value;    Negative predictive value;   

DOI  :  10.1186/s12916-021-02134-x

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY