Genome-Wide Association Study Identifies a Possible Susceptibility Locus for Endometrial Cancer

被引：32

作者：

Long, Jirong ^{[1
,2
]}

Zheng, Wei ^{[1
,2
]}

Xiang, Yong-Bing ^{[4
]}

Lose, Felicity ^{[5
]}

Thompson, Deborah ^{[7
]}

Tomlinson, Ian ^{[8
,9
]}

Yu, Herbert ^{[10
]}

Wentzensen, Nicolas ^{[11
]}

Lambrechts, Diether ^{[12
]}

Doerk, Thilo ^{[13
]}

Dubrowinskaja, Natalia ^{[13
]}

Goodman, Marc T. ^{[14
]}

Salvesen, Helga B. ^{[15
,16
]}

Fasching, Peter A. ^{[17
,19
]}

Scott, Rodney J. ^{[20
,21
]}

Delahanty, Ryan ^{[1
,2
]}

Zheng, Ying ^{[3
]}

O'Mara, Tracy ^{[5
,6
]}

Healey, Catherine S. ^{[7
]}

Hodgson, Shirley ^{[23
]}

Risch, Harvey ^{[10
]}

Yang, Hannah P. ^{[11
]}

Amant, Frederic ^{[12
]}

Turmanov, Nurzhan ^{[13
]}

Schwake, Anita ^{[13
]}

Lurie, Galina ^{[14
]}

Trovik, Jone ^{[15
,16
]}

Beckmann, Matthias W. ^{[17
]}

Ashton, Katie ^{[20
]}

Ji, Bu-Tian ^{[11
]}

Bao, Ping-Ping ^{[3
]}

Howarth, Kimberly ^{[8
,9
]}

Lu, Lingeng ^{[10
]}

Lissowska, Jolanta ^{[24
,25
]}

Coenegrachts, Lieve ^{[12
]}

Kaidarova, Dilyara ^{[26
]}

Duerst, Matthias ^{[27
]}

Thompson, Pamela J. ^{[14
]}

Krakstad, Camilla ^{[15
,16
]}

Ekici, Arif B. ^{[18
]}

Otton, Geoffrey ^{[22
]}

Shi, Jiajun ^{[1
,2
]}

Zhang, Ben ^{[1
,2
]}

Gorman, Maggie ^{[8
,9
]}

Brinton, Louise ^{[11
]}

Coosemans, An ^{[12
]}

Matsuno, Rayna K. ^{[14
]}

Halle, Mari K. ^{[15
,16
]}

Hein, Alexander ^{[17
]}

Proietto, Anthony ^{[22
]}

机构：

[1] Vanderbilt Univ, Sch Med, Div Epidemiol, Dept Med, Nashville, TN 37203 USA

[2] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37203 USA

[3] Shanghai Inst Prevent Med, Shanghai, Peoples R China

[4] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China

[5] Queensland Univ Technol, Div Genet & Populat Hlth, Queensland Inst Med Res, Brisbane, Qld 4001, Australia

[6] Queensland Univ Technol, Canc Program, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia

[7] Univ Cambridge, Dept Oncol, Strangeways Res Lab, Cambridge, England

[8] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[9] Univ Oxford, NIHR Comprehens Biomed Res Ctr, Oxford, England

[10] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, Yale Canc Ctr, New Haven, CT 06510 USA

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

[12] Katholieke Univ Leuven, Div Gynaecol Oncol, Louvain, Belgium

[13] Hannover Med Sch, Gynaecol Res Unit, D-3000 Hannover, Germany

[14] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA

[15] Haukeland Hosp, Dept Obstet & Gynecol, N-5021 Bergen, Norway

[16] Univ Bergen, Dept Clin Med, Bergen, Norway

[17] Univ Hosp Erlangen, Dept Gynecol & Obstet, Erlangen, Germany

[18] Univ Erlangen Nurnberg, Inst Human Genet, Comprehens Canc Ctr Erlangen Nuremberg, Erlangen, Germany

[19] Univ Calif Los Angeles, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90024 USA

[20] Univ Newcastle, Newcastle, NSW 2300, Australia

[21] Hunter Area Pathol Serv, Newcastle, NSW, Australia

[22] Hunter New England Hlth Serv, Newcastle, NSW, Australia

[23] Univ London St Georges Hosp, Sch Med, London SW17 0RE, England

[24] M Sklodowska Curie Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland

[25] Inst Oncol, Warsaw, Poland

[26] State Oncol Inst, Almaty Oncol Ctr, Alma Ata, Kazakhstan

[27] Univ Jena, Dept Gynecol, Jena Univ Hosp, D-6900 Jena, Germany

来源：

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION | 2012年 / 21卷 / 06期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

PROGESTERONE-RECEPTOR GENE; RISK; VARIANTS; CALPAIN; CYP19A1;

D O I：

10.1158/1055-9965.EPI-11-1160

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Genome-wide association studies (GWAS) have identified more than 100 genetic loci for various cancers. However, only one is for endometrial cancer. Methods: We conducted a three-stage GWAS including 8,492 endometrial cancer cases and 16,596 controls. After analyzing 585,963 single-nucleotide polymorphisms (SNP) in 832 cases and 2,682 controls (stage I) from the Shanghai Endometrial Cancer Genetics Study, we selected the top 106 SNPs for in silica replication among 1,265 cases and 5,190 controls from the Australian/British Endometrial Cancer GWAS (stage II). Nine SNPs showed results consistent in direction with stage I with P < 0.1. These nine SNPs were investigated among 459 cases and 558 controls (stage IIIa) and six SNPs showed a direction of association consistent with stages land H. These six SNPs, plus two additional SNPs selected on the basis of linkage disequilibrium and P values in stage II, were investigated among 5,936 cases and 8,166 controls from an additional 11 studies (stage IIIb). Results: SNP rs1202524, near the CAPN9 gene on chromosome 1q42.2, showed a consistent association with endometrial cancer risk across all three stages, with ORs of 1.09 [95% confidence interval (Cl), 1.03-1.16] for the A/G genotype and 1.17(95% Cl, 1.05-1.30) for the GIG genotype (P = 1.6 x 10(-4) in combined analyses of all samples). The association was stronger when limited to the endometrioid subtype, with ORs (95% Cl) of 1.11 (1.04-1.18) and 1.21 (1.08-1.35), respectively (P = 2.4 x 10(-5)). Conclusions: Chromosome 1q42.2 may host an endometrial cancer susceptibility locus. Impact: This study identified a potential genetic locus for endometrial cancer risk. Cancer Epidemiol Biomarkers Prev; 21(6); 980-7. (C) 2012 AACR.

引用

页码：980 / 987

页数：8

共 26 条

[1]

[Anonymous], 2012, GWAS CAT

[2]

[Anonymous], 2012, NIEHS SNP FUNCT PRED

[3]

[Anonymous], 2012, COR CELL REP

[4]

[Anonymous], 2012, ESE FINDER

[5] The crystal structures of human calpains 1 and 9 imply diverse mechanisms of action and auto-inhibition [J].

Davis, Tara L. ;

Walker, John R. ;

Finerty, Patrick J., Jr. ;

Mackenzie, Farrell ;

Newman, Elena M. ;

Dhe-Paganon, Sirano .

JOURNAL OF MOLECULAR BIOLOGY, 2007, 366 (01) :216-229

[6] Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes [J].

Gudmundsson, Julius ;

Sulem, Patrick ;

Steinthorsdottir, Valgerdur ;

Bergthorsson, Jon T. ;

Thorleifsson, Gudmar ;

Manolescu, Andrei ;

Rafnar, Thorunn ;

Gudbjartsson, Daniel ;

Agnarsson, Bjarni A. ;

Baker, Adam ;

Sigurdsson, Asgeir ;

Benediktsdottir, Kristrun R. ;

Jakobsdottir, Margret ;

Blondal, Thorarinn ;

Stacey, Simon N. ;

Helgason, Agnar ;

Gunnarsdottir, Steinunn ;

Olafsdottir, Adalheidur ;

Kristinsson, Kari T. ;

Birgisdottir, Birgitta ;

Ghosh, Shyamali ;

Thorlacius, Steinunn ;

Magnusdottir, Dana ;

Stefansdottir, Gerdur ;

Kristjansson, Kristleifur ;

Bagger, Yu ;

Wilensky, Robert L. ;

Reilly, Muredach P. ;

Morris, Andrew D. ;

Kimber, Charlotte H. ;

Adeyemo, Adebowale ;

Chen, Yuanxiu ;

Zhou, Jie ;

So, Wing-Yee ;

Tong, Peter C. Y. ;

Ng, Maggie C. Y. ;

Hansen, Torben ;

Andersen, Gitte ;

Borch-Johnsen, Knut ;

Jorgensen, Torben ;

Tres, Alejandro ;

Fuertes, Fernando ;

Ruiz-Echarri, Manuel ;

Asin, Laura ;

Saez, Berta ;

van Boven, Erica ;

Klaver, Siem ;

Swinkels, Dorine W. ;

Aben, Katja K. ;

Graif, Theresa .

NATURE GENETICS, 2007, 39 (08) :977-983

[7] Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33 [J].

Houlston, Richard S. ;

Cheadle, Jeremy ;

Dobbins, Sara E. ;

Tenesa, Albert ;

Jones, Angela M. ;

Howarth, Kimberley ;

Spain, Sarah L. ;

Broderick, Peter ;

Domingo, Enric ;

Farrington, Susan ;

Prendergast, James G. D. ;

Pittman, Alan M. ;

Theodoratou, Evi ;

Smith, Christopher G. ;

Olver, Bianca ;

Walther, Axel ;

Barnetson, Rebecca A. ;

Churchman, Michael ;

Jaeger, Emma E. M. ;

Penegar, Steven ;

Barclay, Ella ;

Martin, Lynn ;

Gorman, Maggie ;

Mager, Rachel ;

Johnstone, Elaine ;

Midgley, Rachel ;

Niittymaki, Iina ;

Tuupanen, Sari ;

Colley, James ;

Idziaszczyk, Shelley ;

Thomas, Huw J. W. ;

Lucassen, Anneke M. ;

Evans, D. Gareth R. ;

Maher, Eamonn R. ;

Maughan, Timothy ;

Dimas, Antigone ;

Dermitzakis, Emmanouil ;

Cazier, Jean-Baptiste ;

Aaltonen, Lauri A. ;

Pharoah, Paul ;

Kerr, David J. ;

Carvajal-Carmona, Luis G. ;

Campbell, Harry ;

Dunlop, Malcolm G. ;

Tomlinson, Ian P. M. .

NATURE GENETICS, 2010, 42 (11) :973-U89

[8] The calpain family and human disease [J].

Huang, YH ;

Wang, KKW .

TRENDS IN MOLECULAR MEDICINE, 2001, 7 (08) :355-362

[9] Hormonal contraception and risk of endometrial cancer: a systematic review [J].

Mueck, Alfred O. ;

Seeger, Harald ;

Rabe, Thomas .

[10] Progesterone receptor gene variants and risk of endometrial cancer [J].

O'Mara, Tracy A. ;

Fahey, Paul ;

Ferguson, Kaltin ;

Marquart, Louise ;

Lambrechts, Diether ;

Despierre, Evelyn ;

Vergote, Ignace ;

Amant, Frederic ;

Hall, Per ;

Liu, Jianjun ;

Czene, Kamila ;

Rebbeck, Timothy R. ;

Ahmed, Shahana ;

Dunning, Alison M. ;

Gregory, Catherine S. ;

Shah, Mitul ;

Webb, Penelope M. ;

Spurdle, Amanda B. .

CARCINOGENESIS, 2011, 32 (03) :331-335

← 1 2 3 →