Skip to Content
Discovering the causes of cancer and the means of prevention

Publications Search - Abstract View

Title: Prediction of breast cancer risk by genetic risk factors, overall and by hormone receptor status.
Authors: Hüsing A,  Canzian F,  Beckmann L,  Garcia-Closas M,  Diver WR,  Thun MJ,  Berg CD,  Hoover RN,  Ziegler RG,  Figueroa JD,  Isaacs C,  Olsen A,  Viallon V,  Boeing H,  Masala G,  Trichopoulos D,  Peeters PH,  Lund E,  Ardanaz E,  Khaw KT,  Lenner P,  Kolonel LN,  Stram DO,  Le Marchand L,  McCarty CA,  Buring JE,  Lee IM,  Zhang S,  Lindström S,  Hankinson SE,  Riboli E,  Hunter DJ,  Henderson BE,  Chanock SJ,  Haiman CA,  Kraft P,  Kaaks R,  BPC3
Journal: J Med Genet
Date: 2012 Sep
Branches: EBP, IIB, ITEB, LGS, MEB, OD
PubMed ID: 22972951
PMC ID: PMC3793888
Abstract: OBJECTIVE: There is increasing interest in adding common genetic variants identified through genome wide association studies (GWAS) to breast cancer risk prediction models. First results from such models showed modest benefits in terms of risk discrimination. Heterogeneity of breast cancer as defined by hormone-receptor status has not been considered in this context. In this study we investigated the predictive capacity of 32 GWAS-detected common variants for breast cancer risk, alone and in combination with classical risk factors, and for tumours with different hormone receptor status. MATERIAL AND METHODS: Within the Breast and Prostate Cancer Cohort Consortium, we analysed 6009 invasive breast cancer cases and 7827 matched controls of European ancestry, with data on classical breast cancer risk factors and 32 common gene variants identified through GWAS. Discriminatory ability with respect to breast cancer of specific hormone receptor-status was assessed with the age adjusted and cohort-adjusted concordance statistic (AUROC(a)). Absolute risk scores were calculated with external reference data. Integrated discrimination improvement was used to measure improvements in risk prediction. RESULTS: We found a small but steady increase in discriminatory ability with increasing numbers of genetic variants included in the model (difference in AUROC(a) going from 2.7% to 4%). Discriminatory ability for all models varied strongly by hormone receptor status. DISCUSSION AND CONCLUSIONS: Adding information on common polymorphisms provides small but statistically significant improvements in the quality of breast cancer risk prediction models. We consistently observed better performance for receptor-positive cases, but the gain in discriminatory quality is not sufficient for clinical application.