학술논문

Risk Prediction for Epithelial Ovarian Cancer in 11 United States–Based Case-Control Studies: Incorporation of Epidemiologic Risk Factors and 17 Confirmed Genetic Loci
Document Type
article
Source
American Journal of Epidemiology. 184(8)
Subject
Epidemiology
Health Sciences
Ovarian Cancer
Rare Diseases
Prevention
Cancer
Adult
Aged
Area Under Curve
Carcinoma
Ovarian Epithelial
Case-Control Studies
Female
Genetic Loci
Genetic Predisposition to Disease
Humans
Logistic Models
Middle Aged
Neoplasms
Glandular and Epithelial
Ovarian Neoplasms
Polymorphism
Single Nucleotide
Risk Assessment
Risk Factors
United States
genetic risk polymorphisms
model evaluation
ovarian cancer
risk model
on behalf of the Ovarian Cancer Association Consortium
Mathematical Sciences
Medical and Health Sciences
Language
Abstract
Previously developed models for predicting absolute risk of invasive epithelial ovarian cancer have included a limited number of risk factors and have had low discriminatory power (area under the receiver operating characteristic curve (AUC) < 0.60). Because of this, we developed and internally validated a relative risk prediction model that incorporates 17 established epidemiologic risk factors and 17 genome-wide significant single nucleotide polymorphisms (SNPs) using data from 11 case-control studies in the United States (5,793 cases; 9,512 controls) from the Ovarian Cancer Association Consortium (data accrued from 1992 to 2010). We developed a hierarchical logistic regression model for predicting case-control status that included imputation of missing data. We randomly divided the data into an 80% training sample and used the remaining 20% for model evaluation. The AUC for the full model was 0.664. A reduced model without SNPs performed similarly (AUC = 0.649). Both models performed better than a baseline model that included age and study site only (AUC = 0.563). The best predictive power was obtained in the full model among women younger than 50 years of age (AUC = 0.714); however, the addition of SNPs increased the AUC the most for women older than 50 years of age (AUC = 0.638 vs. 0.616). Adapting this improved model to estimate absolute risk and evaluating it in prospective data sets is warranted.