title: Risk Prediction for Epithelial Ovarian Cancer in 11 United States-Based Case-Control Studies: Incorporation of Epidemiologic Risk Factors and 17 Confirmed Genetic Loci.
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.
authors.forename: Merlise A
authors.initials: MA
authors.lastname: Clyde
authors.forename: Rachel
authors.initials: R
authors.lastname: Palmieri Weber
authors.forename: Edwin S
authors.initials: ES
authors.lastname: Iversen
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Poole
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Doherty
authors.forename: Marc T
authors.initials: MT
authors.lastname: Goodman
authors.forename: Roberta B
authors.initials: RB
authors.lastname: Ness
authors.forename: Harvey A
authors.initials: HA
authors.lastname: Risch
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Rossing
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Terry
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.forename: Alice S
authors.initials: AS
authors.lastname: Whittemore
authors.forename: Hoda
authors.initials: H
authors.lastname: Anton-Culver
authors.forename: Elisa V
authors.initials: EV
authors.lastname: Bandera
authors.forename: Andrew
authors.initials: A
authors.lastname: Berchuck
authors.forename: Michael E
authors.initials: ME
authors.lastname: Carney
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Cramer
authors.forename: Julie M
authors.initials: JM
authors.lastname: Cunningham
authors.forename: Kara L
authors.initials: KL
authors.lastname: Cushing-Haugen
authors.forename: Robert P
authors.initials: RP
authors.lastname: Edwards
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Fridley
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Goode
authors.forename: Galina
authors.initials: G
authors.lastname: Lurie
authors.forename: Valerie
authors.initials: V
authors.lastname: McGuire
authors.forename: Francesmary
authors.initials: F
authors.lastname: Modugno
authors.forename: Kirsten B
authors.initials: KB
authors.lastname: Moysich
authors.forename: Sara H
authors.initials: SH
authors.lastname: Olson
authors.forename: Celeste Leigh
authors.initials: CL
authors.lastname: Pearce
authors.forename: Malcolm C
authors.initials: MC
authors.lastname: Pike
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Rothstein
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Sellers
authors.forename: Weiva
authors.initials: W
authors.lastname: Sieh
authors.forename: Daniel
authors.initials: D
authors.lastname: Stram
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Thompson
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.forename: Kristine G
authors.initials: KG
authors.lastname: Wicklund
authors.forename: Anna H
authors.initials: AH
authors.lastname: Wu
authors.forename: Argyrios
authors.initials: A
authors.lastname: Ziogas
authors.forename: Shelley S
authors.initials: SS
authors.lastname: Tworoger
authors.forename: Joellen M
authors.initials: JM
authors.lastname: Schildkraut
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000209:etiology* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000209:etiology* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D014481:United States
keywords: genetic risk polymorphisms; model evaluation; ovarian cancer; risk model