The Contributions of Breast Density and Common Genetic Variation to Breast Cancer Risk
The Contributions of Breast Density and Common Genetic Variation to Breast Cancer Risk
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DOI：
10.1093/jnci/dju397
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发表时间：
2015-05-01
影响因子：
10.3
通讯作者：
Couch, Fergus J.
中科院分区：
文献类型：
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作者：
Vachon, Celine M.;Pankratz, V. Shane;Couch, Fergus J.
我们使用logistic回归模型评估了76位点多基因风险评分（PRS）和乳腺成像报告和数据系统（BI-RADS）乳腺密度是否是三个研究（1643例患者，2397例对照患者）的独立危险因素。我们将PRS优势比（OR）纳入乳腺癌监测联盟（BCSC）风险预测模型，同时考虑其归因风险，并使用曲线下面积（AUC）统计比较模型之间的5年绝对风险预测。所有统计检验均为双侧检验。在所有三项研究中，BI-RADS密度和PRS是独立的危险因素（P-interaction = .23）。相对于散在纤维腺密度和平均PRS（第二四分位数）的女性，极端密度和最高四分位数PRS的女性风险增加2.7倍（95%可信区间[CI] = 1.74至4.12），而低密度和PRS的女性风险降低（OR = 0.30, 95% CI = 0.18至0.51）。PRS为BCSC模型增加了独立信息（P < .001），并将区分准确率从AUC = 0.66提高到AUC = 0.69。尽管bscc - prs模型在病例对照数据中得到了很好的校准，但需要独立的队列数据来检验普通人群的校准。
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 (2nd 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.