Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer.
Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer.
复制标题
DOI：
10.1038/ng.3341
复制
发表时间：
2015-08
期刊：
影响因子：
30.8
通讯作者：
Klein AP
中科院分区：
文献类型：
--
作者：
Childs EJ;Mocci E;Campa D;Bracci PM;Gallinger S;Goggins M;Li D;Neale RE;Olson SH;Scelo G;Amundadottir LT;Bamlet WR;Bijlsma MF;Blackford A;Borges M;Brennan P;Brenner H;Bueno-de-Mesquita HB;Canzian F;Capurso G;Cavestro GM;Chaffee KG;Chanock SJ;Cleary SP;Cotterchio M;Foretova L;Fuchs C;Funel N;Gazouli M;Hassan M;Herman JM;Holcatova I;Holly EA;Hoover RN;Hung RJ;Janout V;Key TJ;Kupcinskas J;Kurtz RC;Landi S;Lu L;Malecka-Panas E;Mambrini A;Mohelnikova-Duchonova B;Neoptolemos JP;Oberg AL;Orlow I;Pasquali C;Pezzilli R;Rizzato C;Saldia A;Scarpa A;Stolzenberg-Solomon RZ;Strobel O;Tavano F;Vashist YK;Vodicka P;Wolpin BM;Yu H;Petersen GM;Risch HA;Klein AP
胰腺癌是发达国家癌症死亡的第四大原因。BRCA 2（参考文献）、ATM、PALB 2（参考文献）、BRCA 1（参考文献）、STK 11（参考文献）、CDKN 2A和错配修复基因中的遗传性高突变和低突变位点均与风险增加相关。为了确定新的风险位点，我们对9，925例胰腺癌病例和11，569例对照进行了全基因组关联研究，其中包括来自北美，中欧和澳大利亚的9项研究中的4，164例新基因分型病例和3，792例对照。我们确定了三个新的关联区域：17q25.1（LINC 00673，rs 11655237，比值比（OR）= 1.26，95%置信区间（CI）= 1.19- 1.34，P = 1.42 × 10 - 14），7 p13（SUGCT，rs17688601，OR = 0.88，95%CI = 0.84- 0.92，P = 1.41 × 10−8）和3q29（TP63，rs9854771，OR = 0.89，95%CI = 0.85- 0.93，P = 2.35 × 10−8）。我们在2p13.3（ETAA 1，rs 1486134，OR = 1.14，95%CI = 1.09- 1.19，P = 3.36 × 10−9）检测到显著相关性，该区域先前在汉族人群中有提示性证据。我们重复了先前报道的9q34.2（ABO）、13q22.1（KLF 5）、5p15.33（TERT和CLPTM 1）、13q12.2（PDX 1）、1q32.1（NR 5A 2）、7q32.3（LINC-PINT）、16q23.1（BCAR 1）和22q12.1（ZNRF 3）的相关性。我们的研究确定了与胰腺癌风险相关的新位点。
Pancreatic cancer is the fourth leading cause of cancer death in the developed world. Both inherited high-penetrance mutations inBRCA2(ref. ),ATM,PALB2(ref. ),BRCA1(ref. ),STK11(ref. ),CDKN2Aand mismatch-repair genes and low-penetrance loci are associated with increased risk,,,. To identify new risk loci, we performed a genome-wide association study on 9,925 pancreatic cancer cases and 11,569 controls, including 4,164 newly genotyped cases and 3,792 controls in 9 studies from North America, Central Europe and Australia. We identified three newly associated regions: 17q25.1 (LINC00673, rs11655237, odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.19–1.34,P= 1.42 × 10−14), 7p13 (SUGCT, rs17688601, OR = 0.88, 95% CI = 0.84–0.92,P= 1.41 × 10−8) and 3q29 (TP63, rs9854771, OR = 0.89, 95% CI = 0.85–0.93,P= 2.35 × 10−8). We detected significant association at 2p13.3 (ETAA1, rs1486134, OR = 1.14, 95% CI = 1.09–1.19,P= 3.36 × 10−9), a region with previous suggestive evidence in Han Chinese. We replicated previously reported associations at 9q34.2 (ABO), 13q22.1 (KLF5), 5p15.33 (TERTandCLPTM1),, 13q12.2 (PDX1), 1q32.1 (NR5A2), 7q32.3 (LINC-PINT), 16q23.1 (BCAR1) and 22q12.1 (ZNRF3). Our study identifies new loci associated with pancreatic cancer risk.