Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs)

被引：16

作者：

Darabi, Hatef ^{[1
]}

Beesley, Jonathan ^{[2
]}

Droit, Arnaud ^{[3
]}

Kar, Siddhartha ^{[4
]}

Nord, Silje ^{[5
]}

Marjaneh, Mahdi Moradi ^{[2
]}

Soucy, Penny ^{[6
]}

Michailidou, Kyriaki ^{[7
,8
]}

Ghoussaini, Maya ^{[4
]}

Wahl, Hanna Fues ^{[1
]}

Bolla, Manjeet K. ^{[7
]}

Wang, Qin ^{[7
]}

Dennis, Joe ^{[7
]}

Alonso, M. Rosario ^{[9
]}

Andrulis, Irene L. ^{[10
,11
]}

Anton-Culver, Hoda ^{[12
]}

Arndt, Volker ^{[13
]}

Beckmann, Matthias W. ^{[14
]}

Benitez, Javier ^{[15
,16
]}

Bogdanova, Natalia V. ^{[17
]}

Bojesen, Stig E. ^{[18
,19
,20
]}

Brauch, Hiltrud ^{[21
,22
,23
]}

Brenner, Hermann ^{[13
,23
,24
,25
]}

Broeks, Annegien ^{[26
]}

Bruening, Thomas ^{[27
]}

Burwinkel, Barbara ^{[28
,29
]}

Chang-Claude, Jenny ^{[30
,31
]}

Choi, Ji-Yeob ^{[32
,33
]}

Conroy, Don M. ^{[4
]}

Couch, Fergus J. ^{[34
]}

Cox, Angela ^{[35
]}

Cross, Simon S. ^{[36
]}

Czene, Kamila ^{[1
]}

Devilee, Peter ^{[37
,38
]}

Doerk, Thilo ^{[39
]}

Easton, Douglas F. ^{[4
,7
]}

Fasching, Peter A. ^{[14
,40
]}

Figueroa, Jonine ^{[41
,42
]}

Fletcher, Olivia ^{[43
,44
]}

Flyger, Henrik ^{[45
]}

Galle, Eva ^{[46
,47
]}

Garcia-Closas, Montserrat ^{[42
]}

Giles, Graham G. ^{[48
,49
]}

Goldberg, Mark S. ^{[50
,51
]}

Gonzalez-Neira, Anna ^{[15
]}

Guenel, Pascal ^{[52
]}

Haiman, Christopher A. ^{[53
]}

Hallberg, Emily ^{[54
]}

Hamann, Ute ^{[55
]}

Hartman, Mikael ^{[56
,57
]}

机构：

[1] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[2] QIMR Berghofer Med Res Inst, Dept Genet, Brisbane, Qld, Australia

[3] Univ Laval, Ctr Hosp Univ Quebec Res Ctr, Fac Med, Dept Mol Med, Quebec City, PQ, Canada

[4] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England

[5] Oslo Univ Hosp Radiumhosp, Inst Canc Res, Dept Canc Genet, Oslo, Norway

[6] Univ Laval, Ctr Hosp Univ Quebec Res Ctr, Genom Ctr, Quebec City, PQ, Canada

[7] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England

[8] Cyprus Inst Neurol & Genet, Dept Elect Microscopy Mol Pathol, Nicosia, Cyprus

[9] Spanish Natl Canc Res Ctr, Human Canc Genet Program, Human Genotyping CEGEN Unit, Madrid, Spain

[10] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada

[11] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada

[12] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA

[13] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany

[14] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen EMN, Dept Gynecol & Obstet, Erlangen, Germany

[15] Spanish Natl Canc Res Ctr, Human Canc Genet Program, Madrid, Spain

[16] Ctr Invest Red Enfermedades Raras, Valencia, Spain

[17] Hannover Med Sch, Dept Radiat Oncol, Hannover, Germany

[18] Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Herlev, Denmark

[19] Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark

[20] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark

[21] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany

[22] Univ Tubingen, Tubingen, Germany

[23] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany

[24] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany

[25] Natl Ctr Tumor Dis NCT, Heidelberg, Germany

[26] Antoni Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands

[27] Ruhr Univ Bochum, Inst Prevent & Occupat Med German Social Accident, Bochum, Germany

[28] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany

[29] German Canc Res Ctr, Mol Epidemiol Grp, Heidelberg, Germany

[30] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany

[31] Univ Med Ctr Hamburg Eppendorf, UCCH, Hamburg, Germany

[32] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul, South Korea

[33] Seoul Natl Univ, Canc Res Inst, Seoul, South Korea

[34] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA

[35] Univ Sheffield, Dept Oncol & Metab, Sheffield Canc Res, Sheffield, S Yorkshire, England

[36] Univ Sheffield, Acad Unit Pathol, Dept Neurosci, Sheffield, S Yorkshire, England

[37] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands

[38] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands

[39] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany

[40] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA

[41] Univ Edinburgh, Sch Med, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland

[42] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA

[43] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London, England

[44] Inst Canc Res, Div Breast Canc Res, London, England

[45] Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Breast Surg, Herlev, Denmark

[46] Vesalius Res Ctr, Leuven, Belgium

[47] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium

[48] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia

[49] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia

[50] McGill Univ, Dept Med, Montreal, PQ, Canada

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

基金：

英国医学研究理事会; 加拿大健康研究院; 澳大利亚国家健康与医学研究理事会; 美国国家卫生研究院; 新加坡国家研究基金会; 芬兰科学院;

关键词：

SUSCEPTIBILITY LOCI; HUMAN GENOME; RISK LOCUS; ASSOCIATION; EXPRESSION; VARIANTS; REVEALS;

D O I：

10.1038/srep32512

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90-0.94; P = 8.96 x 10(-15))) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 x 10-09, r(2) = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 x 10(-11), r(2) = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus.

引用

页数：14

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