Assessment of clinical validity of a breast cancer risk model combining genetic and clinical information.
Assessment of clinical validity of a breast cancer risk model combining genetic and clinical information.
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DOI：
10.1093/jnci/djq388
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发表时间：
2010-11-03
期刊：
影响因子：
--
通讯作者：
Hinds DA
中科院分区：
文献类型：
--
作者：
Mealiffe ME;Stokowski RP;Rhees BK;Prentice RL;Pettinger M;Hinds DA
Gail模型被广泛用于根据公认的临床风险因素评估浸润性乳腺癌的风险。近年来，大量与乳腺癌风险相关的单核苷酸多态(SNPs)已被发现。然而，目前尚不清楚如何有效地整合临床和遗传风险因素进行风险评估。从文献中选择了7个与乳腺癌风险相关的SNPs，并在妇女健康倡议临床试验中对1664名病例患者和1636名对照受试者的嵌套病例对照队列中的非西班牙裔白人女性进行了基因分型。SNP风险分数是根据之前发布的假设乘法模型的优势比计算得出的。综合风险分数的计算方法是将Gail风险估计值乘以SNP风险分数。用Logistic回归分析Gail风险和SNP风险的独立性。使用Hosmer-Lemesshow检验对相对风险的校准进行评估。使用接受者操作特征曲线来评估综合风险评分的表现。净重分类改进(NRI)被用来评估将女性分为低(1.5%)、中(1.5%-2%)和高(2%)类5年风险的改善情况。所有有统计学意义的检验都是双面的。SNP风险评分几乎独立于盖尔风险。预测和观察到的SNP相对风险之间有很好的一致性。在对接受者操作特征曲线的分析中，联合风险评分更具区分性，其曲线下面积为0.594，而仅盖尔风险曲线下面积为0.557(P<；.001)。5.6%的病例组和2.9%的对照组患者的NRI值为0.085(P=1.0×10−5)。关注中度GAIL风险的女性导致NRI改善0.195(P=8.6x10−5)。将经过验证的常见遗传风险因素与临床风险因素相结合，可使绝经后非西班牙裔白人妇女的乳腺癌风险分类略有改善。通过将重点放在中等风险的妇女身上，分类绩效得到了进一步改善。
The Gail model is widely used for the assessment of risk of invasive breast cancer based on recognized clinical risk factors. In recent years, a substantial number of single-nucleotide polymorphisms (SNPs) associated with breast cancer risk have been identified. However, it remains unclear how to effectively integrate clinical and genetic risk factors for risk assessment. Seven SNPs associated with breast cancer risk were selected from the literature and genotyped in white non-Hispanic women in a nested case–control cohort of 1664 case patients and 1636 control subjects within the Women’s Health Initiative Clinical Trial. SNP risk scores were computed based on previously published odds ratios assuming a multiplicative model. Combined risk scores were calculated by multiplying Gail risk estimates by the SNP risk scores. The independence of Gail risk and SNP risk was evaluated by logistic regression. Calibration of relative risks was evaluated using the Hosmer–Lemeshow test. The performance of the combined risk scores was evaluated using receiver operating characteristic curves. The net reclassification improvement (NRI) was used to assess improvement in classification of women into low (<1.5%), intermediate (1.5%–2%), and high (>2%) categories of 5-year risk. All tests of statistical significance were two-sided. The SNP risk score was nearly independent of Gail risk. There was good agreement between predicted and observed SNP relative risks. In the analysis for receiver operating characteristic curves, the combined risk score was more discriminating, with area under the curve of 0.594 compared with area under the curve of 0.557 for Gail risk alone (P < .001). Classification also improved for 5.6% of case patients and 2.9% of control subjects, showing an NRI value of 0.085 (P = 1.0 × 10−5). Focusing on women with intermediate Gail risk resulted in an improved NRI of 0.195 (P = 8.6 × 10−5). Combining validated common genetic risk factors with clinical risk factors resulted in modest improvement in classification of breast cancer risks in white non-Hispanic postmenopausal women. Classification performance was further improved by focusing on women at intermediate risk.
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作者：
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