Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types.
Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types.
复制标题
DOI：
10.1158/2159-8290.cd-15-1227
复制
发表时间：
2016-09
期刊：
影响因子：
28.2
通讯作者：
Lambrechts D
中科院分区：
文献类型：
--
作者：
Kar SP;Beesley J;Amin Al Olama A;Michailidou K;Tyrer J;Kote-Jarai Z;Lawrenson K;Lindstrom S;Ramus SJ;Thompson DJ;ABCTB Investigators;Kibel AS;Dansonka-Mieszkowska A;Michael A;Dieffenbach AK;Gentry-Maharaj A;Whittemore AS;Wolk A;Monteiro A;Peixoto A;Kierzek A;Cox A;Rudolph A;Gonzalez-Neira A;Wu AH;Lindblom A;Swerdlow A;AOCS Study Group & Australian Cancer Study (Ovarian Cancer);APCB BioResource;Ziogas A;Ekici AB;Burwinkel B;Karlan BY;Nordestgaard BG;Blomqvist C;Phelan C;McLean C;Pearce CL;Vachon C;Cybulski C;Slavov C;Stegmaier C;Maier C;Ambrosone CB;Høgdall CK;Teerlink CC;Kang D;Tessier DC;Schaid DJ;Stram DO;Cramer DW;Neal DE;Eccles D;Flesch-Janys D;Edwards DR;Wokozorczyk D;Levine DA;Yannoukakos D;Sawyer EJ;Bandera EV;Poole EM;Goode EL;Khusnutdinova E;Høgdall E;Song F;Bruinsma F;Heitz F;Modugno F;Hamdy FC;Wiklund F;Giles GG;Olsson H;Wildiers H;Ulmer HU;Pandha H;Risch HA;Darabi H;Salvesen HB;Nevanlinna H;Gronberg H;Brenner H;Brauch H;Anton-Culver H;Song H;Lim HY;McNeish I;Campbell I;Vergote I;Gronwald J;Lubiński J;Stanford JL;Benítez J;Doherty JA;Permuth JB;Chang-Claude J;Donovan JL;Dennis J;Schildkraut JM;Schleutker J;Hopper JL;Kupryjanczyk J;Park JY;Figueroa J;Clements JA;Knight JA;Peto J;Cunningham JM;Pow-Sang J;Batra J;Czene K;Lu KH;Herkommer K;Khaw KT;kConFab Investigators;Matsuo K;Muir K;Offitt K;Chen K;Moysich KB;Aittomäki K;Odunsi K;Kiemeney LA;Massuger LF;Fitzgerald LM;Cook LS;Cannon-Albright L;Hooning MJ;Pike MC;Bolla MK;Luedeke M;Teixeira MR;Goodman MT;Schmidt MK;Riggan M;Aly M;Rossing MA;Beckmann MW;Moisse M;Sanderson M;Southey MC;Jones M;Lush M;Hildebrandt MA;Hou MF;Schoemaker MJ;Garcia-Closas M;Bogdanova N;Rahman N;NBCS Investigators;Le ND;Orr N;Wentzensen N;Pashayan N;Peterlongo P;Guénel P;Brennan P;Paulo P;Webb PM;Broberg P;Fasching PA;Devilee P;Wang Q;Cai Q;Li Q;Kaneva R;Butzow R;Kopperud RK;Schmutzler RK;Stephenson RA;MacInnis RJ;Hoover RN;Winqvist R;Ness R;Milne RL;Travis RC;Benlloch S;Olson SH;McDonnell SK;Tworoger SS;Maia S;Berndt S;Lee SC;Teo SH;Thibodeau SN;Bojesen SE;Gapstur SM;Kjær SK;Pejovic T;Tammela TL;GENICA Network;PRACTICAL consortium;Dörk T;Brüning T;Wahlfors T;Key TJ;Edwards TL;Menon U;Hamann U;Mitev V;Kosma VM;Setiawan VW;Kristensen V;Arndt V;Vogel W;Zheng W;Sieh W;Blot WJ;Kluzniak W;Shu XO;Gao YT;Schumacher F;Freedman ML;Berchuck A;Dunning AM;Simard J;Haiman CA;Spurdle A;Sellers TA;Hunter DJ;Henderson BE;Kraft P;Chanock SJ;Couch FJ;Hall P;Gayther SA;Easton DF;Chenevix-Trench G;Eeles R;Pharoah PD;Lambrechts D
乳腺癌、卵巢癌和前列腺癌与激素有关，可能有共同的遗传基础，但这还没有通过全基因组关联(GWA)研究进行系统的研究。Meta分析结合了这些癌症的最大的GWA荟萃分析数据集，总共112,349例病例和116,421名欧洲血统的对照，全部和成对地在P<；10−8发现了7个新的交叉癌症基因座：3个与所有三种癌症的易感性有关(rs17041869/2q13/BCL2L11；rs7937840/11q12/INCENP；rs1469713/19p13/GATAD2A)，两个乳腺癌和卵巢癌风险基因座(rs200182588/9q31/SMC2；rs8037/15q26/rcCD1)，以及两个乳腺癌和前列腺癌风险基因座(rs1350329/1p34/NSUN4；rs937713/19p13/L3MBLT3)。以前只与一种癌症相关的另外五个区域的指数变异也显示出与第二种癌症类型的明显关联。细胞类型特异性表达、数量性状基因座和增强子-基因相互作用注释表明，在新的基因座上具有潜在的跨癌作用的靶基因。路径分析显示，在三种癌症的荟萃分析中，P<；10−5基因座附近的死亡受体信号基因显著丰富。
Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10−8 seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10−5 in the three-cancer meta-analysis.