Journal of the National Cancer Institute · 2015
The contributions of breast density and common genetic variation to breast cancer risk.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Vachon Celine M, Pankratz V Shane, Scott Christopher G, Haeberle Lothar, Ziv Elad, Jensen Matthew R, Brandt Kathleen R, Whaley Dana H, Olson Janet E, Heusinger Katharina, Hack Carolin C, Jud Sebastian M, Beckmann Matthias W, Schulz-Wendtland Ruediger, Tice Jeffrey A, Norman Aaron D, Cunningham Julie M, Purrington Kristen S, Easton Douglas F, Sellers Thomas A, Kerlikowske Karla, Fasching Peter A, Couch Fergus J
Аннотация
We evaluated whether a 76-locus polygenic risk score (PRS) and Breast Imaging Reporting and Data System (BI-RADS) breast density were independent risk factors within three studies (1643 case patients, 2397 control patients) using logistic regression models. We incorporated the PRS odds ratio (OR) into the Breast Cancer Surveillance Consortium (BCSC) risk-prediction model while accounting for its attributable risk and compared five-year absolute risk predictions between models using area under the curve (AUC) statistics. All statistical tests were two-sided. BI-RADS density and PRS were independent risk factors across all three studies (P interaction = .23). Relative to those with scattered fibroglandular densities and average PRS (2(nd) quartile), women with extreme density and highest quartile PRS had 2.7-fold (95% confidence interval [CI] = 1.74 to 4.12) increased risk, while those with low density and PRS had reduced risk (OR = 0.30, 95% CI = 0.18 to 0.51). PRS added independent information (P < .001) to the BCSC model and improved discriminatory accuracy from AUC = 0.66 to AUC = 0.69. Although the BCSC-PRS model was well calibrated in case-control data, independent cohort data are needed to test calibration in the general population.