Incidence of Breast Cancer and Its Subtypes in Relation to Individual and Multiple Low-Penetrance Genetic Susceptibility Loci
Incidence of Breast Cancer and Its Subtypes in Relation to Individual and Multiple Low-Penetrance Genetic Susceptibility Loci
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DOI：
10.1001/jama.2010.1042
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发表时间：
2010-07-28
影响因子：
120.7
通讯作者：
Lathrop, Mark
中科院分区：
文献类型：
--
作者：
Reeves, Gillian K.;Travis, Ruth C.;Lathrop, Mark
背景乳腺癌及其亚型的风险如何依赖于低风险易感基因位点，单独或联合的证据有限。目的分析乳腺癌的风险，总体和肿瘤亚型，与14个单独的单核苷酸多态性（SNP）以前与疾病相关，并与多基因风险评分。设计，设置，10306名乳腺癌患者的研究（平均诊断年龄，58岁）和10393名无乳腺癌的妇女，她们在2005-2008年在一项英国妇女的大型前瞻性研究中提供了用于基因分型的血液样本;主要结果测量单个SNP的估计每个等位基因优势比（OR），和70岁时乳腺癌的累积发病率与基于4，7，结果FGFR 2-rs 2981582和TNRC 9-rs3803662与乳腺癌的比值比最大，对于这2个SNP，雌激素受体（ER）阳性的患者比ER阴性的患者显著更高，在我们的数据和所有已发表数据的荟萃分析中（ER阳性与ER阴性疾病的合并每个等位基因OR [95%置信区间]：FGFR 2为1.30 [1.26-1.33] vs 1.05 [1.01-1.10];相互作用P
Context There is limited evidence on how the risk of breast cancer and its subtypes depend on low-penetrance susceptibility loci, individually or in combination.Objective To analyze breast cancer risk, overall and by tumor subtype, in relation to 14 individual single-nucleotide polymorphisms (SNPs) previously linked to the disease, and in relation to a polygenic risk score.Design, Setting, and Participants Study of 10 306 women with breast cancer (mean age at diagnosis, 58 years) and 10 393 women without breast cancer who in 2005-2008 provided blood samples for genotyping in a large prospective study of UK women; and meta-analysis of these results and of other published results.Main Outcome Measures Estimated per-allele odds ratio (OR) for individual SNPs, and cumulative incidence of breast cancer to age 70 years in relation to a polygenic risk score based on the 4, 7, or 10 SNPs most strongly associated with risk.Results Odds ratios for breast cancer were greatest for FGFR2-rs2981582 and TNRC9-rs3803662 and, for these 2 SNPs, were significantly greater for estrogen receptor (ER)-positive than for ER-negative disease, both in our data and in meta-analyses of all published data (pooled per-allele ORs [95% confidence intervals] for ER-positive vs ER-negative disease: 1.30 [1.26-1.33] vs 1.05 [1.01-1.10] for FGFR2; interaction P