A survey of microRNA single nucleotide polymorphisms identifies novel breast cancer susceptibility loci in a case-control, population-based study of African-American women.
A survey of microRNA single nucleotide polymorphisms identifies novel breast cancer susceptibility loci in a case-control, population-based study of African-American women.
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DOI：
10.1186/s13058-018-0964-4
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发表时间：
2018-06-05
期刊：
影响因子：
--
通讯作者：
Olshan AF
中科院分区：
文献类型：
--
作者：
Bensen JT;Graff M;Young KL;Sethupathy P;Parker J;Pecot CV;Currin K;Haddad SA;Ruiz-Narváez EA;Haiman CA;Hong CC;Sucheston-Campbell LE;Zhu Q;Liu S;Yao S;Bandera EV;Rosenberg L;Lunetta KL;Ambrosone CB;Palmer JR;Troester MA;Olshan AF
MicroRNA (miRNA) 调节基因表达并影响癌症。 miRNA 的初级转录物 (pri-miRNA) 的注释很少，并且人们对 miRNA 基因和乳腺癌 (BC) 中种系变异的作用知之甚少。我们试图在非裔美国 (AA) 女性中鉴定与 BC 风险和肿瘤亚型相关的种系 miRNA 变异。在非裔美国人乳腺癌流行病学和风险 (AMBER) 联盟的领导下，来自 AA 女性 BC 的四项研究的基因分型和估算数据被合并成一个最终数据集，其中包含 8350 名女性的 224,188 个 miRNA 基因单核苷酸多态性 (SNP)：其中 3663 名病例和 4687 名对照。鉴定了 DNA 元素百科全书 (ENCODE) 第 1 层细胞类型和人胰岛中表达的 566 个 miRNA 基因的初级 miRNA 序列。使用逻辑回归对 BC 整体状态和肿瘤亚型进行关联分析。一个新的 BC 信号由四个 SNP（rs9913477、rs1428882938、rs28585511 和 rs7502931）定位于 17q25.3 的 8.6 kb 区域，并且在多重检验校正后仍具有统计学显着性（比值比 (OR) = 1.44，95% 置信区间 (CI) = 1.26–1.65；p = 3.15 × 10−7；错误发现率（FDR） = 0.03）。这些 SNP 位于基因组位置，其中包括非编码 miRNA 基因 MIR3065 的预测初级转录物和脑特异性血管生成抑制剂 1 相关蛋白 2 (BAIAP2) 基因的第一个内含子。此外，染色体 1p32.3、5q32 和 3p25.1 上的 miRNA 相关 SNP 分别是激素受体、管腔与基底样和 HER2 富集状态的最强信号。第二阶段的基因分型（1397 个 BC 病例，2418 个对照）包括 8.6 kb 区域中的两个 SNP，用于验证和荟萃分析。虽然 rs4969239 和 rs9913477 均未经过验证，但当使用原始数据集进行荟萃分析时，它们与 BC 的关联在方向上保持一致（OR = 1.29，95% CI = 1.16–1.44（p = 4.18 × 10–6）和 OR = 1.33，95% CI = 1.17–1.51（p = 1.6 × 10–5），分别）。种系遗传变异表明 MIR3065 可能在 AA 女性的 BC 发育和异质性中发挥重要作用。需要进一步研究以确定这些 SNP 的潜在功能效应。这项研究有助于我们了解 AA 女性的 BC 风险，并强调评估人类基因组基因密集区域变异的复杂性。本文的在线版本 (10.1186/s13058-018-0964-4) 包含补充材料，可供授权用户使用。
MicroRNAs (miRNAs) regulate gene expression and influence cancer. Primary transcripts of miRNAs (pri-miRNAs) are poorly annotated and little is known about the role of germline variation in miRNA genes and breast cancer (BC). We sought to identify germline miRNA variants associated with BC risk and tumor subtype among African-American (AA) women. Under the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium, genotyping and imputed data from four studies on BC in AA women were combined into a final dataset containing 224,188 miRNA gene single nucleotide polymorphisms (SNPs) for 8350 women: 3663 cases and 4687 controls. The primary miRNA sequence was identified for 566 miRNA genes expressed in Encyclopedia of DNA Elements (ENCODE) Tier 1 cell types and human pancreatic islets. Association analysis was conducted using logistic regression for BC status overall and by tumor subtype. A novel BC signal was localized to an 8.6-kb region of 17q25.3 by four SNPs (rs9913477, rs1428882938, rs28585511, and rs7502931) and remained statistically significant after multiple test correction (odds ratio (OR) = 1.44, 95% confidence interval (CI) = 1.26–1.65; p = 3.15 × 10−7; false discovery rate (FDR) = 0.03). These SNPs reside in a genomic location that includes both the predicted primary transcript of the noncoding miRNA gene MIR3065 and the first intron of the gene for brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2). Furthermore, miRNA-associated SNPs on chromosomes 1p32.3, 5q32, and 3p25.1 were the strongest signals for hormone receptor, luminal versus basal-like, and HER2 enrichment status, respectively. A second phase of genotyping (1397 BC cases, 2418 controls) that included two SNPs in the 8.6-kb region was used for validation and meta-analysis. While neither rs4969239 nor rs9913477 was validated, when meta-analyzed with the original dataset their association with BC remained directionally consistent (OR = 1.29, 95% CI = 1.16–1.44 (p = 4.18 × 10–6) and OR = 1.33, 95% CI = 1.17–1.51 (p = 1.6 × 10–5), respectively). Germline genetic variation indicates that MIR3065 may play an important role in BC development and heterogeneity among AA women. Further investigation to determine the potential functional effects of these SNPs is warranted. This study contributes to our understanding of BC risk in AA women and highlights the complexity in evaluating variation in gene-dense regions of the human genome. The online version of this article (10.1186/s13058-018-0964-4) contains supplementary material, which is available to authorized users.
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DOI：
10.1158/1055-9965.epi-15-0874
发表时间：
2016-03
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Allott EH;Cohen SM;Geradts J;Sun X;Khoury T;Bshara W;Zirpoli GR;Miller CR;Hwang H;Thorne LB;O'Connor S;Tse CK;Bell MB;Hu Z;Li Y;Kirk EL;Bethea TN;Perou CM;Palmer JR;Ambrosone CB;Olshan AF;Troester MA
通讯作者：
Troester MA
影响因子：
4
作者：
Bandera EV;Chandran U;Zirpoli G;McCann SE;Ciupak G;Ambrosone CB
通讯作者：
Ambrosone CB
影响因子：
14.9
作者：
Griffiths-Jones, S
通讯作者：
Griffiths-Jones, S
影响因子：
30.8
作者：
Bentwich, I;Avniel, A;Bentwich, Z
通讯作者：
Bentwich, Z
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y