Genetic variation in the Hippo pathway and breast cancer risk in women of African ancestry.
Genetic variation in the Hippo pathway and breast cancer risk in women of African ancestry.
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DOI：
10.1002/mc.22845
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发表时间：
2018-10
影响因子：
4.6
通讯作者：
Zheng Y
中科院分区：
文献类型：
--
作者：
Wang S;Huo D;Ogundiran TO;Ojengbede O;Zheng W;Nathanson KL;Nemesure B;Ambs S;Olopade OI;Zheng Y
Hippo通路内的基因表达变化被发现与乳腺癌中的大肿瘤尺寸和转移相关。该途径基因中遗传变异的综合效应可能在乳腺癌的发生中发挥因果作用。我们检测了7,086个SNP，（r2 < 0.8）在35个Hippo通路基因中，使用来自Root Consortium的乳腺癌全基因组关联研究的数据，该研究包括来自尼日利亚、美利坚合众国和巴巴多斯的3，686名非洲血统的参与者：1，657例病例（403例雌激素受体阳性[ER+]，374例ER-）和2，029例对照。基因水平的分析进行了大规模的遗传关联研究调整年龄，研究地点和前四个特征向量的主成分分析，使用改进的AdaJoint测试。SNP水平分析采用Logistic回归进行。Hippo通路与ER+乳腺癌的风险显著相关（通路水平P = 0.019），WWC 1（Padj = 0.04）是主导基因。无WWC 1时，通路水平显著性丢失（P = 0.12）。经基因水平调整后多重比较，WWC 1基因rs 147106204为最显著的SNP（OR = 0.53，95%CI = 0.41-0.70，Padj = 0.025）。我们发现了Hippo通路中的遗传变异与ER+乳腺癌之间存在关联的证据。此外，WWC 1被确定为最重要的遗传易感性位点，突出了在未充分研究的人群中进行乳腺癌遗传流行病学研究的重要性。
Gene expression changes within the Hippo pathway were found to be associated with large tumor size and metastasis in breast cancer. The combined effect of genetic variants in genes of this pathway may have a causal role in breast cancer development. We examined 7,086 SNPs that were not highly correlated (r2 < 0.8) in 35 Hippo pathway genes using data from the genome-wide association study of breast cancer from the Root Consortium, which includes 3,686 participants of African ancestry from Nigeria, United States of America, and Barbados: 1,657 cases (403 estrogen receptor-positive [ER+], 374 ER−) and 2,029 controls. Gene-level analyses were conducted using improved AdaJoint test for large-scale genetic association studies adjusting for age, study site and the first four eigenvectors from the principal component analysis. SNP-level analyses were conducted with logistic regression. The Hippo pathway was significantly associated with risk of ER+ breast cancer (pathway-level P = 0.019), with WWC1 (Padj = 0.04) being the leading gene. The pathway-level significance was lost without WWC1 (P = 0.12). rs147106204 in the WWC1 gene was the most statistically significant SNP after gene-level adjustment for multiple comparisons (OR = 0.53, 95% CI = 0.41–0.70, Padj = 0.025). We found evidence of an association between genetic variations in the Hippo pathway and ER+ breast cancer. Moreover, WWC1 was identified as the most important genetic susceptibility locus highlighting the importance of genetic epidemiology studies of breast cancer in understudied populations.
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影响因子：
64.8
作者：
Britschgi A;Duss S;Kim S;Couto JP;Brinkhaus H;Koren S;De Silva D;Mertz KD;Kaup D;Varga Z;Voshol H;Vissieres A;Leroy C;Roloff T;Stadler MB;Scheel CH;Miraglia LJ;Orth AP;Bonamy GM;Reddy VA;Bentires-Alj M
通讯作者：
Bentires-Alj M
影响因子：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M
影响因子：
28.4
作者：
Huo D;Hu H;Rhie SK;Gamazon ER;Cherniack AD;Liu J;Yoshimatsu TF;Pitt JJ;Hoadley KA;Troester M;Ru Y;Lichtenberg T;Sturtz LA;Shelley CS;Benz CC;Mills GB;Laird PW;Shriver CD;Perou CM;Olopade OI
通讯作者：
Olopade OI
影响因子：
6.4
作者：
Nemesure, Barbara;Wu, Suh-Yuh;Hennis, Anselm J.
通讯作者：
Hennis, Anselm J.
影响因子：
4.7
作者：
Huo, Dezheng;Zheng, Yonglan;Olopade, Olufunmilayo I.
通讯作者：
Olopade, Olufunmilayo I.