Home LiteratureArticle Details
PMID: 18794855 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Sequence variant on 8q24 confers susceptibility to urinary bladder cancer.

Nature genetics ·Vol. 40 ·No. 11 ·2008-11-00 ·Pages 1307-12

Kiemeney LA, Thorlacius S, Sulem P, Geller F, Aben KK, Stacey SN, Gudmundsson J, Jakobsdottir M, Bergthorsson JT, Sigurdsson A, Blondal T, Witjes JA, Vermeulen SH, Hulsbergen-van de Kaa CA, Swinkels DW, Ploeg M, Cornel EB, Vergunst H, Thorgeirsson TE, Gudbjartsson D, Gudjonsson SA, Thorleifsson G, Kristinsson KT, Mouy M, Snorradottir S, Placidi D, Campagna M, Arici C, Koppova K, Gurzau E, Rudnai P, Kellen E, Polidoro S, Guarrera S, Sacerdote C, Sanchez M, Saez B, Valdivia G, Ryk C, de Verdier P, Lindblom A, Golka K, Bishop DT, Knowles MA, Nikulasson S, Petursdottir V, Jonsson E, Geirsson G, Kristjansson B, Mayordomo JI, Steineck G, Porru S, Buntinx F, Zeegers MP, Fletcher T, Kumar R, Matullo G, Vineis P, Kiltie AE, Gulcher JR, Thorsteinsdottir U, Kong A, Rafnar T, Stefansson K

Abstract

We conducted a genome-wide SNP association study on 1,803 urinary bladder cancer (UBC) cases and 34,336 controls from Iceland and The Netherlands and follow up studies in seven additional case-control groups (2,165 cases and 3,800 controls). The strongest association was observed with allele T of rs9642880 on chromosome 8q24, 30 kb upstream of MYC (allele-specific odds ratio (OR) = 1.22; P = 9.34 x 10(-12)). Approximately 20% of individuals of European ancestry are homozygous for rs9642880[T], and their estimated risk of developing UBC is 1.49 times that of noncarriers. No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers. A weaker signal, but nonetheless of genome-wide significance, was captured by rs710521[A] located near TP63 on chromosome 3q28 (allele-specific OR = 1.19; P = 1. 15 x 10(-7)).

MeSH Terms
Adult Aged Aged, 80 and over Base Sequence Case-Control Studies Chromosomes, Human, Pair 3/genetics Chromosomes, Human, Pair 8/genetics Female Genetic Markers Genetic Predisposition to Disease Humans Linkage Disequilibrium/genetics Male Middle Aged Mutation/genetics Urinary Bladder Neoplasms/genetics
Chemicals
Genetic Markers
Authors & Affiliations
64 authors, click to expand affiliations / ORCID
Kiemeney Lambertus A
Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands.
Thorlacius Steinunn
Sulem Patrick
Geller Frank
Aben Katja K H
Stacey Simon N
Gudmundsson Julius
Jakobsdottir Margret
Bergthorsson Jon T
Sigurdsson Asgeir
Blondal Thorarinn
Witjes J Alfred
Vermeulen Sita H
Hulsbergen-van de Kaa Christina A
Swinkels Dorine W
Ploeg Martine
Cornel Erik B
Vergunst Henk
Thorgeirsson Thorgeir E
Gudbjartsson Daniel
Gudjonsson Sigurjon A
Thorleifsson Gudmar
Kristinsson Kari T
Mouy Magali
Snorradottir Steinunn
Placidi Donatella
Campagna Marcello
Arici Cecilia
Koppova Kvetoslava
Gurzau Eugene
Rudnai Peter
Kellen Eliane
Polidoro Silvia
Guarrera Simonetta
Sacerdote Carlotta
Sanchez Manuel
Saez Berta
Valdivia Gabriel
Ryk Charlotta
de Verdier Petra
Lindblom Annika
Golka Klaus
Bishop D Timothy
Knowles Margaret A
Nikulasson Sigfus
Petursdottir Vigdis
Jonsson Eirikur
Geirsson Gudmundur
Kristjansson Baldvin
Mayordomo Jose I
Steineck Gunnar
Porru Stefano
Buntinx Frank
Zeegers Maurice P
Fletcher Tony
Kumar Rajiv
Matullo Giuseppe
Vineis Paolo
Kiltie Anne E
Gulcher Jeffrey R
Thorsteinsdottir Unnur
Kong Augustine
Rafnar Thorunn
Stefansson Kari
References (29)
29 references, click to expand
  1. myc family oncogenes in the development of normal and neoplastic cells.
    Adv Cancer Res. 1991;57:1-46 PMID: 1950701
  2. The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee.
    Am J Surg Pathol. 1998 Dec;22(12):1435-48 PMID: 9850170
  3. The gene encoding phosphodiesterase 4D confers risk of ischemic stroke.
    Nat Genet. 2003 Oct;35(2):131-8 PMID: 14517540
  4. Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs.
    Hum Mol Genet. 2007 Jan 1;16(1):36-49 PMID: 17135278
  5. The c-myc insulator element and matrix attachment regions define the c-myc chromosomal domain.
    Mol Cell Biol. 2003 Dec;23(24):9338-48 PMID: 14645543
  6. Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer.
    Nat Genet. 2007 Jul;39(7):865-9 PMID: 17529974
  7. Genetics of gene expression surveyed in maize, mouse and man.
    Nature. 2003 Mar 20;422(6929):297-302 PMID: 12646919
  8. Genetics of gene expression and its effect on disease.
    Nature. 2008 Mar 27;452(7186):423-8 PMID: 18344981
  9. Statistical aspects of the analysis of data from retrospective studies of disease.
    J Natl Cancer Inst. 1959 Apr;22(4):719-48 PMID: 13655060
  10. Genetic alterations in urothelial bladder carcinoma: an updated review.
    Cancer. 2006 Mar 15;106(6):1205-16 PMID: 16470587
  11. A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25.
    Nature. 2008 Apr 3;452(7187):633-7 PMID: 18385738
  12. A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21.
    Nat Genet. 2007 Aug;39(8):984-8 PMID: 17618284
  13. Genome-wide prediction of mammalian enhancers based on analysis of transcription-factor binding affinity.
    Cell. 2006 Jan 13;124(1):47-59 PMID: 16413481
  14. Haplotype relative risks: an easy reliable way to construct a proper control sample for risk calculations.
    Ann Hum Genet. 1987 Jul;51(3):227-33 PMID: 3500674
  15. Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24.
    Nat Genet. 2007 May;39(5):631-7 PMID: 17401366
  16. Segregation analysis of urothelial cell carcinoma.
    Eur J Cancer. 2006 Jul;42(10):1428-33 PMID: 16737809
  17. Cancer as a complex phenotype: pattern of cancer distribution within and beyond the nuclear family.
    PLoS Med. 2004 Dec;1(3):e65 PMID: 15630470
  18. Loss of p63 expression is associated with tumor progression in bladder cancer.
    Am J Pathol. 2002 Oct;161(4):1199-206 PMID: 12368193
  19. Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1.
    Nat Genet. 2008 May;40(5):616-22 PMID: 18385676
  20. Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes.
    Nat Genet. 2007 Aug;39(8):977-83 PMID: 17603485
  21. Genome-wide association study of prostate cancer identifies a second risk locus at 8q24.
    Nat Genet. 2007 May;39(5):645-9 PMID: 17401363
  22. Genome-wide association study identifies novel breast cancer susceptibility loci.
    Nature. 2007 Jun 28;447(7148):1087-93 PMID: 17529967
  23. Genomic control for association studies.
    Biometrics. 1999 Dec;55(4):997-1004 PMID: 11315092
  24. Familial aggregation of urothelial cell carcinoma.
    Int J Cancer. 2002 Mar 10;98(2):274-8 PMID: 11857419
  25. A common inversion under selection in Europeans.
    Nat Genet. 2005 Feb;37(2):129-37 PMID: 15654335
  26. A variant associated with nicotine dependence, lung cancer and peripheral arterial disease.
    Nature. 2008 Apr 3;452(7187):638-642 PMID: 18385739
  27. Risk of bladder cancer associated with family history of cancer: do low-penetrance polymorphisms account for the increase in risk?
    Cancer Epidemiol Biomarkers Prev. 2007 Aug;16(8):1595-600 PMID: 17684133
  28. Impaired p63 expression associates with poor prognosis and uroplakin III expression in invasive urothelial carcinoma of the bladder.
    Clin Cancer Res. 2003 Nov 15;9(15):5501-7 PMID: 14654529
  29. A common variant associated with prostate cancer in European and African populations.
    Nat Genet. 2006 Jun;38(6):652-8 PMID: 16682969
Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.229
Published
2008-11-00
Epub
2008-00-14
Pages
1307-12
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC4539560
Subset
IM
Grants
Cancer Research UK · A4994 · United Kingdom
NIDA NIH HHS · R01 DA017932 · United States
NIDA NIH HHS · R01-DA017932 · United States
Corrections
CommentIn
PMID: 19650218
CommentIn
PMID: 19650230
External Links
PubMed source DOI: 10.1038/ng.229 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2