Risk Prediction for Epithelial Ovarian Cancer in 11 United States-Based Case-Control Studies: Incorporation of Epidemiologic Risk Factors and 17 Confirmed Genetic Loci

Am J Epidemiol. 2016 Oct 15;184(8):579-589. doi: 10.1093/aje/kww091. Epub 2016 Oct 3.

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.

Keywords: genetic risk polymorphisms; model evaluation; ovarian cancer; risk model.

MeSH terms

  • Adult
  • Aged
  • Area Under Curve
  • Carcinoma, Ovarian Epithelial
  • Case-Control Studies
  • Female
  • Genetic Loci / genetics*
  • Genetic Predisposition to Disease
  • Humans
  • Logistic Models*
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / etiology*
  • Neoplasms, Glandular and Epithelial / genetics
  • Ovarian Neoplasms / etiology*
  • Ovarian Neoplasms / genetics
  • Polymorphism, Single Nucleotide
  • Risk Assessment / methods
  • Risk Factors
  • United States

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