GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

被引：280

作者：

Pharoah, Paul D. P. ^{[1
,2
]}

Tsai, Ya-Yu ^{[3
]}

Ramus, Susan J. ^{[4
]}

Phelan, Catherine M. ^{[3
]}

Goode, Ellen L. ^{[5
]}

Lawrenson, Kate ^{[4
]}

Buckley, Melissa ^{[3
]}

Fridley, Brooke L. ^{[5
]}

Tyrer, Jonathan P. ^{[1
]}

Shen, Howard ^{[4
]}

Weber, Rachel ^{[6
]}

Karevan, Rod ^{[4
]}

Larson, Melissa C. ^{[7
]}

Song, Honglin ^{[1
]}

Tessier, Daniel C. ^{[8
,9
,10
]}

Bacot, Francois ^{[8
,9
,10
]}

Vincent, Daniel ^{[8
,9
,10
]}

Cunningham, Julie M. ^{[11
]}

Dennis, Joe ^{[2
]}

Dicks, Ed ^{[1
]}

Aben, Katja K. ^{[12
,13
]}

Anton-Culver, Hoda ^{[14
]}

Antonenkova, Natalia ^{[15
]}

Armasu, Sebastian M. ^{[7
]}

Baglietto, Laura ^{[16
,17
]}

Bandera, Elisa V. ^{[18
]}

Beckmann, Matthias W. ^{[19
]}

Birrer, Michael J. ^{[20
,21
]}

Bloom, Greg ^{[3
]}

Bogdanova, Natalia ^{[22
]}

Brenton, James D. ^{[23
]}

Brinton, Louise A. ^{[24
]}

Brooks-Wilson, Angela ^{[25
]}

Brown, Robert ^{[26
]}

Butzow, Ralf ^{[27
,28
]}

Campbell, Ian ^{[29
,30
]}

Carney, Michael E. ^{[31
]}

Carvalho, Renato S.

Chang-Claude, Jenny ^{[32
]}

Chen, Y. Anne ^{[3
]}

Chen, Zhihua ^{[3
]}

Chow, Wong-Ho ^{[33
]}

Cicek, Mine S. ^{[5
]}

Coetzee, Gerhard ^{[34
]}

Cook, Linda S. ^{[35
]}

Cramer, Daniel W. ^{[36
,37
,38
]}

Cybulski, Cezary ^{[39
]}

Dansonka-Mieszkowska, Agnieszka ^{[40
,41
]}

Despierre, Evelyn ^{[42
]}

Doherty, Jennifer A. ^{[43
]}

机构：

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

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

[3] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Canc Epidemiol, Div Populat Sci, Tampa, FL 33682 USA

[4] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA

[5] Mayo Clin, Dept Hlth Sci Res, Div Epidemiol, Rochester, MN USA

[6] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA

[7] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA

[8] McGill Univ, Ctr Technol, Montreal, PQ, Canada

[9] McGill Univ, Montreal, PQ, Canada

[10] Genome Quebec Innovat Ctr, Montreal, PQ, Canada

[11] Mayo Clin, Dept Lab Med & Pathol, Div Anat Pathol, Rochester, MN USA

[12] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & Hlth Technol Assessment, NL-6525 ED Nijmegen, Netherlands

[13] Comprehens Canc Ctr Netherlands, Utrecht, Netherlands

[14] Univ Calif Irvine, Sch Med, Dept Epidemiol, Ctr Canc Genet Res & Prevent, Irvine, CA 92717 USA

[15] NN Aleksandrov Byelorussian Inst Oncol & Med Radi, Minsk, BELARUS

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

[17] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia

[18] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA

[19] Univ Erlangen Nurnberg, Dept Gynecol & Obstet, Univ Hosp Erlangen, Ctr Comprehens Canc, D-91054 Erlangen, Germany

[20] Harvard Univ, Sch Med, Dept Med, Boston, MA USA

[21] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA

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

[23] Li Ka Shing Ctr, Cambridge Res Inst, Cambridge, England

[24] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[25] British Columbia Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada

[26] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London, England

[27] Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki, Finland

[28] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland

[29] Peter MacCallum Canc Ctr, Div Res, Canc Genet Lab, Melbourne, Vic, Australia

[30] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia

[31] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI 96822 USA

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

[33] NCI, Div Canc Etiol & Genet, Bethesda, MD 20892 USA

[34] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Microbiol & Prevent Med, Los Angeles, CA 90033 USA

[35] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA

[36] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA

[37] Harvard Univ, Sch Med, Boston, MA USA

[38] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[39] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland

[40] Maria Sklodowska Curie Mem Canc Ctr, Dept Mol Pathol, Warsaw, Poland

[41] Inst Oncol, Warsaw, Poland

[42] Leuven Canc Inst, Dept Obstet & Gynaecol, Div Gynecol Oncol, Louvain, Belgium

[43] Geisel Sch Med Dartmouth, Sect Biostat & Epidemiol, Lebanon, NH USA

[44] Dr Horst Schmidt Kliniken Wiesbaden, Dept Gynecol & Gynecol Oncol, Wiesbaden, Germany

[45] Kliniken Essen Mitte Evang Huyssens Stiftung Knap, Dept Gynecol & Gynecol Oncol, Essen, Germany

[46] Jena Univ Hosp, Dept Gynecol, Jena, Germany

[47] Univ Southampton, Fac Med, Southampton Univ Hosp, Southampton SO9 5NH, Hants, England

[48] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA

[49] Magee Womens Res Inst, Womens Canc Program, Pittsburgh, PA USA

[50] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany

来源：

NATURE GENETICS | 2013年 / 45卷 / 04期

基金：

英国惠康基金;

关键词：

GENOME-WIDE ASSOCIATION; RISK; EXPRESSION; GENE; NEBULETTE; CARCINOMA; 19P13; MYC;

D O I：

10.1038/ng.2564

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 x 10(-9)) and 10p12 (rs1243180, P = 1.8 x 10(-8)) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 x 10(-10)). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian cancer.

引用

页码：362 / 370

页数：9

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