Genome-wide association study identifies multiple loci associated with bladder cancer risk

被引：118

作者：

Figueroa, Jonine D. ^{[1
]}

Ye, Yuanqing ^{[2
,3
]}

Siddiq, Afshan ^{[4
,5
,6
]}

Garcia-Closas, Montserrat ^{[1
,7
]}

Chatterjee, Nilanjan ^{[1
]}

Prokunina-Olsson, Ludmila ^{[1
]}

Cortessis, Victoria K. ^{[8
,9
]}

Kooperberg, Charles ^{[10
]}

Cussenot, Olivier ^{[11
,12
]}

Benhamou, Simone ^{[13
,14
]}

Prescott, Jennifer ^{[15
,16
,17
,18
,19
,20
]}

Porru, Stefano ^{[21
]}

Dinney, Colin P. ^{[3
]}

Malats, Nuria ^{[22
]}

Baris, Dalsu ^{[1
]}

Purdue, Mark ^{[1
]}

Jacobs, Eric J. ^{[23
]}

Albanes, Demetrius ^{[1
]}

Wang, Zhaoming ^{[24
]}

Deng, Xiang ^{[24
]}

Chung, Charles C. ^{[24
]}

Tang, Wei ^{[1
]}

Bueno-De-Mesquita, H. Bas ^{[25
,26
]}

Trichopoulos, Dimitrios ^{[17
,27
,28
]}

Ljungberg, Borje ^{[29
]}

Clavel-Chapelon, Frangoise ^{[30
]}

Weiderpass, Elisabete ^{[31
,32
,33
,34
]}

Krogh, Vittorio ^{[35
]}

Dorronsoro, Miren ^{[36
,37
]}

Travis, Ruth ^{[38
]}

Tjonneland, Anne ^{[39
]}

Brenan, Paul ^{[40
]}

Chang-Claude, Jenny ^{[41
]}

Riboli, Elio ^{[4
,5
,6
]}

Conti, David ^{[8
]}

Gago-Dominguez, Manuela ^{[42
]}

Stern, Mariana C. ^{[8
]}

Pike, Malcolm C. ^{[43
]}

Van den Berg, David ^{[8
]}

Yuan, Jian-Min ^{[44
]}

Hohensee, Chancellor ^{[9
]}

Rodabough, Rebecca ^{[9
]}

Cancel-Tassin, Geraldine ^{[10
,11
,45
]}

Roupret, Morgan ^{[10
,11
,45
]}

Comperat, Eva ^{[10
,11
,45
]}

Chen, Constance ^{[15
,16
,17
,18
,19
]}

De Vivo, Immaculata ^{[14
,15
,16
,17
,18
,19
]}

Giovannucci, Edward ^{[15
,16
,17
,18
,19
]}

Hunter, David J. ^{[14
,15
,16
,17
,18
,19
,46
]}

Kraft, Peter ^{[15
,16
,17
,18
,19
]}

机构：

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

[2] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA

[4] Univ London Imperial Coll Sci Technol & Med, London, England

[5] Human Genet Fdn HuGeF, London, England

[6] Inst Canc Res, London SW3 6JB, England

[7] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England

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

[9] Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA

[10] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA

[11] Tenon Hosp, AP HP, Dept Urol, Paris, France

[12] Ctr Rech Pathol Prostat, Paris, France

[13] Fdn Jean Dausset, CEPH, INSERM, U946, Paris, France

[14] Inst Gustave Roussy, CNRS, UMR8200, Villejuif, France

[15] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA

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

[17] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Dept Epidemiol, Boston, MA 02115 USA

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

[19] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[20] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[21] Univ Brescia, Dept Med & Surg Specialties, I-25121 Brescia, Italy

[22] Spanish Natl Canc Res Ctr CNIO, Madrid, Spain

[23] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA

[24] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA

[25] NatL Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands

[26] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands

[27] Acad Athens, Bur Epidemiol Res, Athens, Greece

[28] Kaisareias, Hellen Hlth Fdn, Athens, Greece

[29] Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden

[30] Ctr Res Epidemiol & Populat Hlth CESP, INSERM, Villejuif, France

[31] Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway

[32] Canc Registry Norway, Dept Res, Oslo, Norway

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

[34] Samfundet Folkhalsan, Helsinki, Finland

[35] Fdn IRCCS Ist Nazl Tumori, Milan, Italy

[36] Hlth Dept Basque Reg, BioDonostia Res Inst, Pubilc Hlth Div Gipuzkoa, San Sebastian, Spain

[37] CIBERESP, Madrid, Spain

[38] Univ Oxford, Canc Epidemiol Unit, Oxford, England

[39] Danish Canc Soc Res Ctr, Copenhagen, Denmark

[40] Int Agcy Res Canc, F-69372 Lyon, France

[41] DKFZ, Heidelberg, Germany

[42] Complejo Hospitalario Univ Santiago, Galician Fdn Genom Med, Genom Med Grp, Serv Galego Saude SERGAS,Inst Invest Sanitaria Sa, Santiago De Compostela, Spain

[43] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA

[44] Univ Pittsburgh Canc Inst, Pittsburgh, PA USA

[45] Univ Paris 06, ONCOTYPE URO, GRC 5, Paris, France

[46] Broad Inst Harvard & MIT, Embridge, MA USA

[47] Univ Padua, Dept Cardiac Thorac & Vasc Sci, Padua, Italy

[48] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA

[49] Informat Management Syst, Silver Spring, MD USA

[50] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain

来源：

HUMAN MOLECULAR GENETICS | 2014年 / 23卷 / 05期

基金：

英国惠康基金; 美国国家卫生研究院; 英国医学研究理事会;

关键词：

NAT2 SLOW ACETYLATION; SUSCEPTIBILITY LOCI; CONFERS SUSCEPTIBILITY; GENETIC POLYMORPHISMS; COLORECTAL-CANCER; SEQUENCE VARIANT; TELOMERE LENGTH; MESSENGER-RNA; LUNG-CANCER; GSTM1; NULL;

D O I：

10.1093/hmg/ddt519

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 x 10(-5) was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 x 10(-9)) and rs907611 on 11p15.5 (P = 4.11 x 10(-8)). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 x 10(-7)) and rs4510656 on 6p22.3 (P = 6.98 x 10(-7)); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.

引用

页码：1387 / 1398

页数：12

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