Discriminatory accuracy from single-nucleotide polymorphisms in models to predict breast cancer risk.
Discriminatory accuracy from single-nucleotide polymorphisms in models to predict breast cancer risk.
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DOI：
10.1093/jnci/djn180
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发表时间：
2008-07-16
期刊：
影响因子：
--
通讯作者：
Gail MH
中科院分区：
文献类型：
--
作者：
Gail MH
寻找与疾病相关的共同等位基因的一个目的是利用它们来改进预测个性化疾病风险的模型。两项全基因组关联研究和一项候选基因研究最近在独立样本中发现了七种常见的单核苷酸多态(SNPs)，它们与乳腺癌风险有关。这7个SNP分别位于FGFR2、TNRC9、MAP3K1、LSP1、CASP8、染色体8q区和2q35区。我使用这些研究中对相对风险和等位基因频率的估计来估计这些SNPs可以在多大程度上提高以接受者工作特征曲线(AUC)下的面积衡量的判别准确率。包含这7个SNP的模型(AuC=0.574)和包含14个此类SNP的假设模型(AuC=0.604)的判别准确率低于国家癌症研究所的乳腺癌风险评估工具(BCRAT)，该工具基于月经初潮和首次活产年龄、乳腺癌家族史和乳房活检检查史(AuC=0.607)。将7个SNP添加到BCRAT中可以提高判别准确率，AUC值为0.632，然而，这比添加乳房X光检查密度的改善要小。因此，与BCRAT相比，这七个常见等位基因提供的判别准确性较低，但有可能适度提高BCRAT的判别准确性。迄今为止的经验和定量论证表明，在全基因组关联研究中，需要大幅增加乳腺癌病例和对照受试者的数量，以找到足够的SNP来实现高度的区别性准确性。
One purpose for seeking common alleles that are associated with disease is to use them to improve models for projecting individualized disease risk. Two genome-wide association studies and a study of candidate genes recently identified seven common single-nucleotide polymorphisms (SNPs) that were associated with breast cancer risk in independent samples. These seven SNPs were located in FGFR2, TNRC9, MAP3K1, LSP1, CASP8, chromosomal region 8q, and chromosomal region 2q35. I used estimates of relative risks and allele frequencies from these studies to estimate how much these SNPs could improve discriminatory accuracy measured as the area under the receiver operating characteristic curve (AUC). A model with these seven SNPs (AUC = 0.574) and a hypothetical model with 14 such SNPs (AUC = 0.604) have less discriminatory accuracy than a model, the National Cancer Institute's Breast Cancer Risk Assessment Tool (BCRAT), which is based on ages at menarche and at first live birth, family history of breast cancer, and history of breast biopsy examinations (AUC = 0.607). Adding the seven SNPs to BCRAT improved discriminatory accuracy to an AUC of 0.632, which was, however, less than the improvement from adding mammographic density. Thus, these seven common alleles provide less discriminatory accuracy than BCRAT but have the potential to improve the discriminatory accuracy of BCRAT modestly. Experience to date and quantitative arguments indicate that a huge increase in the numbers of case patients with breast cancer and control subjects would be required in genome-wide association studies to find enough SNPs to achieve high discriminatory accuracy.
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影响因子：
5
作者：
Pepe, MS;Janes, H;Newcomb, P
通讯作者：
Newcomb, P
DOI：
10.1093/jnci/djj332
发表时间：
2006-09-06
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Chen, Jinbo;Pee, David;Gail, Mitchell H.
通讯作者：
Gail, Mitchell H.
影响因子：
2.1
作者：
Gail, Mitchell H.;Pfeiffer, Ruth M.;Pee, David
通讯作者：
Pee, David
DOI：
10.1093/jnci/91.21.1829
发表时间：
1999-11-03
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Gail, MH;Costantino, JP;Vogel, V
通讯作者：
Vogel, V
影响因子：
10.3
作者：
GAIL, MH;BRINTON, LA;MULVIHILL, JJ
通讯作者：
MULVIHILL, JJ