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dc.contributor.authorKoutros, S
dc.contributor.authorBaris, D
dc.contributor.authorFischer, A
dc.contributor.authorTang, W
dc.contributor.authorGarcia-Closas, M
dc.contributor.authorKaragas, MR
dc.contributor.authorSchwenn, M
dc.contributor.authorJohnson, A
dc.contributor.authorFigueroa, J
dc.contributor.authorWaddell, R
dc.contributor.authorProkunina-Olsson, L
dc.contributor.authorRothman, N
dc.contributor.authorSilverman, DT
dc.date.accessioned2018-08-03T13:30:31Z
dc.date.issued2013-12-15
dc.identifier.citationInternational journal of cancer, 2013, 133 (12), pp. 3008 - 3013
dc.identifier.issn0020-7136
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2262
dc.identifier.eissn1097-0215
dc.identifier.doi10.1002/ijc.28325
dc.description.abstractGenome-wide association studies (GWAS) identified associations between markers within the solute carrier family 14 (urea transporter), member 1 (SLC14A1) gene and risk of bladder cancer. SLC14A1 defines the Kidd blood groups in erythrocytes and is also involved in concentration of the urine in the kidney. We evaluated the association between a representative genetic variant (rs10775480) of SLC14A1 and urine concentration, as measured by urinary specific gravity (USG), in a subset of 275 population-based controls enrolled in the New England Bladder Cancer Study. Overnight urine samples were collected, and USG was measured using refractometry. Analysis of covariance was used to estimate adjusted least square means for USG in relation to rs10775480. We also examined the mRNA expression of both urea transporters, SLC14A1 and SLC14A2, in a panel of human tissues. USG was decreased with each copy of the rs10775480 risk T allele (p-trend = 0.011) with a significant difference observed for CC vs. TT genotypes (p-value(tukey) = 0.024). RNA-sequencing in the bladder tissue showed high expression of SLC14A1 and the absence of SLC14A2, while both transporters were expressed in the kidney. We suggest that the molecular phenotype of this GWAS finding is the genotype-specific biological activity of SLC14A1 in the bladder tissue. Our data suggest that SLC14A1 could be a unique urea transporter in the bladder that has the ability to influence urine concentration and that this mechanism might explain the increased bladder cancer susceptibility associated with rs10775480.
dc.formatPrint-Electronic
dc.format.extent3008 - 3013
dc.languageeng
dc.language.isoeng
dc.publisherWILEY-BLACKWELL
dc.subjectHumans
dc.subjectMembrane Transport Proteins
dc.subjectCase-Control Studies
dc.subjectGenotype
dc.subjectPhenotype
dc.subjectSpecific Gravity
dc.subjectAdult
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectUrinary Bladder Neoplasms
dc.titleDifferential urinary specific gravity as a molecular phenotype of the bladder cancer genetic association in the urea transporter gene, SLC14A1.
dc.typeJournal Article
dcterms.dateAccepted2013-05-22
rioxxterms.versionofrecord10.1002/ijc.28325
rioxxterms.licenseref.startdate2013-12
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfInternational journal of cancer
pubs.issue12
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Molecular Epidemiology
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Molecular Epidemiology
pubs.publication-statusPublished
pubs.volume133
pubs.embargo.termsNot known
icr.researchteamMolecular Epidemiology
dc.contributor.icrauthorGarcia-Closas, Montserrat


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