Validation of a Genetic-Enhanced Risk Prediction Model for Colorectal Cancer in a Large Community-Based Cohort

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F23%3A00582277" target="_blank" >RIV/68378041:_____/23:00582277 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11140/23:10469402

Výsledek na webu

<a href="https://aacrjournals.org/cebp/article-abstract/32/3/353/718479/Validation-of-a-Genetic-Enhanced-Risk-Prediction?redirectedFrom=fulltext" target="_blank" >https://aacrjournals.org/cebp/article-abstract/32/3/353/718479/Validation-of-a-Genetic-Enhanced-Risk-Prediction?redirectedFrom=fulltext</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1158/1055-9965.EPI-22-0817" target="_blank" >10.1158/1055-9965.EPI-22-0817</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Validation of a Genetic-Enhanced Risk Prediction Model for Colorectal Cancer in a Large Community-Based Cohort

Popis výsledku v původním jazyce

Background: Polygenic risk scores (PRS) which summarize individuals' genetic risk profile may enhance targeted colorectal cancer screening. A critical step towards clinical implementation is rigorous external validations in large community-based cohorts. This study externally validated a PRS-enhanced colorectal cancer risk model comprising 140 known colorectal cancer loci to provide a comprehensive assessment on prediction performance.Methods: The model was developed using 20,338 individuals and externally validated in a community-based cohort (n = 85,221). We validated predicted 5-year absolute colorectal cancer risk, including calibration using expected-to-observed case ratios (E/O) and cal-ibration plots, and discriminatory accuracy using time-dependent AUC. The PRS-related improvement in AUC, sensitivity and specificity were assessed in individuals of age 45 to 74 years (screening-eligible age group) and 40 to 49 years with no endoscopy history (younger-age group).Results: In European-ancestral individuals, the predicted 5-year risk calibrated well [E/O = 1.01, 95% confidence interval (CI), 0.91- 1.13] and had high discriminatory accuracy (AUC = 0.73, 95% CI, 0.71-0.76). Adding the PRS to a model with age, sex, family and endoscopy history improved the 5-year AUC by 0.06 (P < 0.001) and 0.14 (P = 0.05) in the screening-eligible age and younger-age groups, respectively. Using a risk-threshold of 5-year SEER colorectal cancer incidence rate at age 50 years, adding the PRS had a similar sensitivity but improved the specificity by 11% (P < 0.001) in the screening -eligible age group. In the younger-age group it improved the sensitivity by 27% (P = 0.04) with similar specificity.Conclusions: The proposed PRS-enhanced model provides a well-calibrated 5-year colorectal cancer risk prediction and improves discriminatory accuracy in the external cohort.Impact: The proposed model has potential utility in risk -stratified colorectal cancer prevention.

Název v anglickém jazyce

Validation of a Genetic-Enhanced Risk Prediction Model for Colorectal Cancer in a Large Community-Based Cohort

Popis výsledku anglicky

Background: Polygenic risk scores (PRS) which summarize individuals' genetic risk profile may enhance targeted colorectal cancer screening. A critical step towards clinical implementation is rigorous external validations in large community-based cohorts. This study externally validated a PRS-enhanced colorectal cancer risk model comprising 140 known colorectal cancer loci to provide a comprehensive assessment on prediction performance.Methods: The model was developed using 20,338 individuals and externally validated in a community-based cohort (n = 85,221). We validated predicted 5-year absolute colorectal cancer risk, including calibration using expected-to-observed case ratios (E/O) and cal-ibration plots, and discriminatory accuracy using time-dependent AUC. The PRS-related improvement in AUC, sensitivity and specificity were assessed in individuals of age 45 to 74 years (screening-eligible age group) and 40 to 49 years with no endoscopy history (younger-age group).Results: In European-ancestral individuals, the predicted 5-year risk calibrated well [E/O = 1.01, 95% confidence interval (CI), 0.91- 1.13] and had high discriminatory accuracy (AUC = 0.73, 95% CI, 0.71-0.76). Adding the PRS to a model with age, sex, family and endoscopy history improved the 5-year AUC by 0.06 (P < 0.001) and 0.14 (P = 0.05) in the screening-eligible age and younger-age groups, respectively. Using a risk-threshold of 5-year SEER colorectal cancer incidence rate at age 50 years, adding the PRS had a similar sensitivity but improved the specificity by 11% (P < 0.001) in the screening -eligible age group. In the younger-age group it improved the sensitivity by 27% (P = 0.04) with similar specificity.Conclusions: The proposed PRS-enhanced model provides a well-calibrated 5-year colorectal cancer risk prediction and improves discriminatory accuracy in the external cohort.Impact: The proposed model has potential utility in risk -stratified colorectal cancer prevention.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cancer Epidemiology Biomarkers & Prevention

ISSN

1055-9965

e-ISSN

1538-7755

Svazek periodika

32

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

353-362

Kód UT WoS článku

000989768900001

EID výsledku v databázi Scopus

2-s2.0-85149999165