European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene.

TitleEuropean genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene.
Publication TypeJournal Article
Year of Publication2011
AuthorsRafnar T, Vermeulen SH, Sulem P, Thorleifsson G, Aben KK, Witjes AJ, Grotenhuis AJ, Verhaegh GW, Hulsbergen-van de Kaa CA, Besenbacher S, Gudbjartsson D, Stacey SN, Gudmundsson J, Johannsdottir H, Bjarnason H, Zanon C, Helgadottir H, Jonasson J G, Tryggvadottir L, Jonsson E, Geirsson G, Nikulasson S, Petursdottir V, Bishop TD, Chung-Sak S, Choudhury A, Elliott F, Barrett JH, Knowles MA, de Verdier PJ, Ryk C, Lindblom A, Rudnai P, Gurzau E, Koppova K, Vineis P, Polidoro S, Guarrera S, Sacerdote C, Panadero A, Sanz-Velez JI, Sanchez M, Valdivia G, Garcia-Prats MD, Hengstler JG, Selinski S, Gerullis H, Ovsiannikov D, Khezri A, Aminsharifi A, Malekzadeh M, van den Berg LH, Ophoff RA, Veldink JH, Zeegers MP, Kellen E, Fostinelli J, Andreoli D, Arici C, Porru S, Buntinx F, Ghaderi A, Golka K, Mayordomo JI, Matullo G, Kumar R, Steineck G, Kiltie AE, Kong A, Thorsteinsdottir U, Stefansson K, Kiemeney LA
JournalHum Mol Genet
Volume20
Issue21
Pagination4268-81
Date Published2011 Nov 1
ISSN1460-2083
KeywordsAdult, Aged, Aged, 80 and over, Chromosomes, Human, Pair 18, Disease Progression, European Continental Ancestry Group, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Membrane Transport Proteins, Middle Aged, Polymorphism, Single Nucleotide, Reproducibility of Results, Risk Factors, Urinary Bladder Neoplasms, Young Adult
Abstract

Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from the Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 × 10(-11). SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the 'urogenous contact hypothesis' that urine production and voiding frequency modify the risk of UBC.

DOI10.1093/hmg/ddr303
Alternate JournalHum. Mol. Genet.
PubMed ID21750109