A genome-wide association study identifies new susceptibility loci for esophageal adenocarcinoma and Barrett's esophagus.
A genome-wide association study identifies new susceptibility loci for esophageal adenocarcinoma and Barrett's esophagus.
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DOI：
10.1038/ng.2796
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发表时间：
2013-12
期刊：
影响因子：
30.8
通讯作者：
Vaughan, Thomas L.
中科院分区：
文献类型：
--
作者：
Levine, David M.;Ek, Weronica E.;Zhang, Rui;Liu, Xinxue;Onstad, Lynn;Sather, Cassandra;Lao-Sirieix, Pierre;Gammon, Marilie D.;Corley, Douglas A.;Shaheen, Nicholas J.;Bird, Nigel C.;Hardie, Laura J.;Murray, Liam J.;Reid, Brian J.;Chow, Wong-Ho;Risch, Harvey A.;Nyren, Olof;Ye, Weimin;Liu, Geoffrey;Romero, Yvonne;Bernstein, Leslie;Wu, Anna H.;Casson, Alan G.;Chanock, Stephen J.;Harrington, Patricia;Caldas, Isabel;Debiram-Beecham, Irene;Caldas, Carlos;Hayward, Nicholas K.;Pharoah, Paul D.;Fitzgerald, Rebecca C.;MacGregor, Stuart;Whiteman, David C.;Vaughan, Thomas L.
食管癌是一种发病率上升、生存率低的癌症。大多数此类癌症发生在特殊的肠化生上皮，这是巴雷特食管的诊断。在一项全基因组关联研究中，我们将食管腺癌病例（n= 2390）和癌前Barrett食管患者（n= 3175）与10120名对照者分为2期进行比较。对于合并病例组，我们确定了三个新的关联。第一个是19p13 (rs10419226:P= 3.6 × 10−10)inCRTC1（编码creb调节的转录辅助激活因子），其异常激活与致癌活性相关。第二个是在barx1的9q22 (rs11789015:P= 1.0 × 10−9)，它编码一个在食管规范中重要的转录因子。第三个基因位于3p14位点（rs2687201:P= 5.5 × 10−9），靠近调控食道发育的转录因子foxp1。我们还改进了先前报道的与Barrett食管的关联，该关联位于推定的肿瘤抑制基因efoxf1at 16q24附近，并将我们的研究结果扩展到现在的食管腺癌。
Esophageal adenocarcinoma is a cancer with rising incidence and poor survival. Most such cancers arise in a specialized intestinal metaplastic epithelium, which is diagnostic of Barrett's esophagus. In a genome-wide association study, we compared esophageal adenocarcinoma cases (n= 2,390) and individuals with precancerous Barrett's esophagus (n= 3,175) with 10,120 controls in 2 phases. For the combined case group, we identified three new associations. The first is at 19p13 (rs10419226:P= 3.6 × 10−10) inCRTC1(encoding CREB-regulated transcription coactivator), whose aberrant activation has been associated with oncogenic activity. A second is at 9q22 (rs11789015:P= 1.0 × 10−9) inBARX1, which encodes a transcription factor important in esophageal specification. A third is at 3p14 (rs2687201:P= 5.5 × 10−9) near the transcription factorFOXP1, which regulates esophageal development. We also refine a previously reported association with Barrett's esophagus near the putative tumor suppressor geneFOXF1at 16q24 and extend our findings to now include esophageal adenocarcinoma.
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影响因子：
82.9
作者：
Altarejos, Judith Y.;Goebel, Naomi;Conkright, Michael D.;Inotiel, Hiroshi;Xie, Jianxin;Arias, Carlos M.;Sawchenko, Paul E.;Montminy, Marc
通讯作者：
Montminy, Marc
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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：
30.8
作者：
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影响因子：
3.5
作者：
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通讯作者：
Wei, Qingyi
影响因子：
6.4
作者：
Dura, Polat;van Veen, Elke M.;Peters, Wilbert H. M.
通讯作者：
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