Genetic variations in EGFR and ERBB4 increase susceptibility to cervical cancer.
Genetic variations in EGFR and ERBB4 increase susceptibility to cervical cancer.
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DOI：
10.1016/j.ygyno.2013.07.113
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发表时间：
2013-11
影响因子：
4.7
通讯作者：
Rader JS
中科院分区：
文献类型：
--
作者：
Ma D;Hovey RL;Zhang Z;Fye S;Huettner PC;Borecki IB;Rader JS
遗传的基因变异有助于子宫颈癌的易感性。我们研究了人表皮生长因子受体（ErbB）家族的单核苷酸多态性（snp）与宫颈癌的关系。我们使用传播不平衡试验（TDT）寻找ERBB家族成员EGFR、ERBB2、ERBB3和ERBB4中标签单核苷酸多态性（tssnp）在大量浸润性和原位宫颈癌女性及其亲生父母（628三人组）中的过度传播。该研究使用了Ilumina GoldenGate分析的一组三人组（244个），其中snp达到P< 0.05的snp由TaqMan在628个组合中重新检测。我们还探讨了不同ERBB等位基因的协同效应。基于单SNP TDT测试，我们确定了16个在发现阶段显著的SNP，并且在联合复制集中，TaqMan可检测的14个SNP中有6个在宫颈癌女性中显著过传。4个snp位于EGFR的内含子1上，2个snp位于ERBB4的内含子24上。EGFR变异位于内含子1上的多个增强子、沉默子和先前鉴定的功能共同多态性附近。我们的数据为内含子1 EGFR变异和内含子24 ERBB4变异参与调节原位和侵袭性宫颈癌发展的风险提供了证据。这些变异应该在其他人群中进行检验，并需要进行功能研究来证实这一假设。
Inherited genetic variability contributes to susceptibility to cervical cancer. We investigated the association of single nucleotide polymorphisms (SNPs) in the human epidermal growth factor receptor (ErbB) family with cervical cancer. We used the transmission disequilibrium test (TDT) to look for excessive transmission of tag single nucleotide polymorphisms (tSNPs) in ERBB family members EGFR, ERBB2, ERBB3, and ERBB4 in a large sample of women with invasive and in situ cervical cancer and their biological parents (628 trios). The study used a discovery set of trios (244) analyzed by Ilumina GoldenGate in which SNPs reaching a P< .05 were re-tested by TaqMan in the combined set of 628. We also explored collaborative effects of different ERBB alleles. Based on single SNP TDT tests we identified 16 SNPs significant in the discover stage and six of 14 SNPs that could be assayed by TaqMan were significantly overtransmitted in women with cervical cancer in the combined replication set. Four SNPs were located in intron 1 of EGFR and two SNPs in intron 24 of ERBB4 The EGFR variants are located near multiple enhancers, silencers, and the previously identified functional common polymorphisms in intron 1. Our data provide evidence for the involvement of intron 1 EGFR variants and intron 24 ERBB4 variants in modulating risk for the development of in situ and invasive cervical cancer. These variants should be examined in additional populations and functional studies would be needed to confirm this hypothesis.
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影响因子：
11.5
作者：
Brandt, Burkhard;Meyer-Staeckling, Soenke;Buerger, Horst
通讯作者：
Buerger, Horst
影响因子：
11.5
作者：
Halle, Cathinka;Lando, Malin;Lyng, Heidi
通讯作者：
Lyng, Heidi
DOI：
10.1097/pgp.0b013e3181eb2fcb
发表时间：
2011-01-01
影响因子：
2.4
作者：
Brustmann, Hermann;Hinterholzer, Susanne;Brunner, Andreas
通讯作者：
Brunner, Andreas
DOI：
10.1158/1055-9965.epi-09-0886
发表时间：
2010-03
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：
Hu X;Zhang Z;Ma D;Huettner PC;Massad LS;Nguyen L;Borecki I;Rader JS
通讯作者：
Rader JS
影响因子：
11.2
作者：
Brandt, B;Hermann, S;Chang-Claude, J
通讯作者：
Chang-Claude, J