Evaluation of associations between genetically predicted circulating protein biomarkers and breast cancer risk.
Evaluation of associations between genetically predicted circulating protein biomarkers and breast cancer risk.
复制标题
评估基因预测的循环蛋白生物标志物与乳腺癌风险之间的关联。
DOI：
10.1002/ijc.32542
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发表时间：
2020
影响因子：
6.4
通讯作者：
García-Closas,Montserra
中科院分区：
文献类型：
--
作者：
Shu,Xiang;Bao,Jiandong;Wu,Lang;Long,Jirong;Shu,Xiao-Ou;Guo,Xingyi;Yang,Yaohua;Michailidou,Kyriaki;Bolla,ManjeetK;Wang,Qin;Dennis,Joe;Andrulis,IreneL;Castelao,JoseE;Dörk,Thilo;Gago-Dominguez,Manuela;García-Closas,Montserra
据报道，少数循环蛋白质与乳腺癌风险相关，结果不一致。在此，我们试图鉴定乳腺癌的新蛋白质生物标志物，整合基因组学和蛋白质组学数据。在乳腺癌协会联盟（BCAC）中，我们评估了122，977例病例和105，974例欧洲后裔对照，遗传预测浓度> 1，400种循环蛋白与乳腺癌风险的关系。我们使用来自大规模蛋白质数量性状基因座（pQTL）分析的数据作为我们的研究工具。从BCAC获得这些与乳腺癌风险相关的pQTL变体的汇总统计量，并使用逆方差加权法估计每种蛋白质的比值比（OR）。我们通过仪器分析鉴定了56种与乳腺癌风险显著相关的蛋白质（错误发现率<0.05）。其中，32个的浓度受到接近乳腺癌易感基因座（ABO，9q34.2）的变异的影响。其中许多蛋白质，如胰岛素受体，胰岛素样生长因子受体1和其他膜受体（OR：0.82- 1.18，p值：6.96 × 10−4-3.28 × 10−8），与胰岛素抵抗和雌激素受体信号通路有关。在其他基因座鉴定的蛋白质包括参与生物过程如酒精和脂质代谢、蛋白水解、细胞凋亡、免疫调节和细胞运动和增殖的蛋白质。在英国生物库数据中观察到22种蛋白质的一致关联（p< 0.05）。该研究确定了乳腺癌的潜在新生物标志物，但需要进一步的研究来复制我们的发现。
A small number of circulating proteins have been reported to be associated with breast cancer risk, with inconsistent results. Herein, we attempted to identify novel protein biomarkers for breast cancerviathe integration of genomics and proteomics data. In the Breast Cancer Association Consortium (BCAC), with 122,977 cases and 105,974 controls of European descendants, we evaluated the associations of the genetically predicted concentrations of >1,400 circulating proteins with breast cancer risk. We used data from a large‐scale protein quantitative trait loci (pQTL) analysis as our study instrument. Summary statistics for these pQTL variants related to breast cancer risk were obtained from the BCAC and used to estimate odds ratios (OR) for each protein using the inverse‐variance weighted method. We identified 56 proteins significantly associated with breast cancer risk by instrumental analysis (false discovery rate <0.05). Of these, the concentrations of 32 were influenced by variants close to a breast cancer susceptibility locus (ABO, 9q34.2). Many of these proteins, such as insulin receptor, insulin‐like growth factor receptor 1 and other membrane receptors (OR: 0.82–1.18,pvalues: 6.96 × 10−4–3.28 × 10−8), are linked to insulin resistance and estrogen receptor signaling pathways. Proteins identified at other loci include those involved in biological processes such as alcohol and lipid metabolism, proteolysis, apoptosis, immune regulation and cell motility and proliferation. Consistent associations were observed for 22 proteins in the UK Biobank data (p< 0.05). The study identifies potential novel biomarkers for breast cancer, but further investigation is needed to replicate our findings.