Evaluation of polygenic risk scores for predicting breast and prostate cancer risk.
Evaluation of polygenic risk scores for predicting breast and prostate cancer risk.
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DOI：
10.1002/gepi.20600
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发表时间：
2011-09
影响因子：
2.1
通讯作者：
Kraft, Peter
中科院分区：
文献类型：
--
作者：
Machiela, Mitchell J.;Chen, Chia-Yen;Chen, Constance;Chanock, Stephen J.;Hunter, David J.;Kraft, Peter
最近，多基因风险评分已被证明与某些复杂疾病有关。该方法基于在独立基因座上计数与疾病相关的多个等位基因的贡献，而不需要令人信服的证据表明每个基因座已经实现了确定的全基因组统计学显著性。多基因风险评分是否有助于预测常见癌症的风险尚不清楚。我们从训练数据集中与乳腺癌或前列腺癌相关的遗传标记列表中建立了多基因风险评分，并评估了这些评分是否可以改善独立测试样本中这些特定癌症的当前遗传预测。我们使用了来自护士健康研究的1，145例乳腺癌病例和1，142例对照的全基因组关联数据，以及来自前列腺癌、肺癌、结直肠癌和卵巢癌筛查试验的1，164例前列腺癌病例和1，113例对照。使用10倍交叉验证来建立和评估具有10至60，000个独立单核苷酸多态性（SNP）的多基因风险评分。对于乳腺癌和前列腺癌，仅包括已发表的风险等位基因的模型使ROC曲线下面积的交叉验证估计值最大化（乳腺癌为0.53，前列腺癌为0.57）。我们没有发现使用常见变异的多基因风险评分比重复SNP评分改善乳腺癌和前列腺癌风险预测的显著证据。
Recently, polygenic risk scores have been shown to be associated with certain complex diseases. The approach has been based on the contribution of counting multiple alleles associated with disease across independent loci, without requiring compelling evidence that every locus had already achieved definitive genome-wide statistical significance. Whether polygenic risk scores assist in the prediction of risk of common cancers is unknown. We built polygenic risk scores from lists of genetic markers prioritized by their association with breast or prostate cancer in a training data set and evaluated whether these scores could improve current genetic prediction of these specific cancers in independent test samples. We used genome-wide association data on 1,145 breast cancer cases and 1,142 controls from the Nurses’ Health Study and 1,164 prostate cancer cases and 1,113 controls from the Prostate Lung Colorectal and Ovarian Cancer Screening Trial. Ten-fold cross validation was used to build and evaluate polygenic risk scores with 10 to 60,000 independent single nucleotide polymorphisms (SNPs). For both breast and prostate cancer, the models that included only published risk alleles maximized the cross-validation estimate of the area under the ROC curve (0.53 for breast and 0.57 for prostate). We found no significant evidence that polygenic risk scores using common variants improved risk prediction for breast and prostate cancer over replicated SNP scores.
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DOI：
10.1016/s0197-2456(00)00097-0
发表时间：
2000-12-01
期刊：
CONTROLLED CLINICAL TRIALS
影响因子：
--
作者：
Gohagan, JK;Prorok, PC;Kramer, BS
通讯作者：
Kramer, BS
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Stacey, Simon N.;Manolescu, Andrei;Stefansson, Kari
通讯作者：
Stefansson, Kari
影响因子：
3.5
作者：
Evans, David M.;Visscher, Peter M.;Wray, Naomi R.
通讯作者：
Wray, Naomi R.
影响因子：
45.3
作者：
Tworoger, Shelley S.;Eliassen, A. Heather;Hankinson, Susan E.
通讯作者：
Hankinson, Susan E.