A genome-wide association study of bladder cancer identifies a new susceptibility locus within SLC14A1, a urea transporter gene on chromosome 18q12.3

Montserrat Garcia-closas, Yuanqing Ye, Nathaniel Rothman, Jonine D. Figueroa, Núria Malats, Colin P. Dinney, Nilanjan Chatterjee, Ludmila Prokunina-olsson, Zhaoming Wang, Jie Lin, Francisco X. Real, Kevin B. Jacobs, Dalsu Baris, Michael Thun, Immaculata De vivo, Demetrius Albanes, Mark P. Purdue, Manolis Kogevinas, Ashish M. Kamat, Seth P. LernerH. Barton grossman, Jian Gu, Xia Pu, Amy Hutchinson, Yi Ping Fu, Laurie Burdett, Meredith Yeager, Wei Tang, Adonina Tardón, Consol Serra, Alfredo Carrato, Reina García-closas, Josep Lloreta, Alison Johnson, Molly Schwenn, Margaret R. Karagas, Alan Schned, Gerald Andriole, Robert Grubb, Amanda Black, Eric J. Jacobs, W. Ryan diver, Susan M. Gapstur, Stephanie J. Weinstein, Jarmo Virtamo, David J. Hunter, Neil Caporaso, Maria Teresa landi, Joseph F. Fraumeni, Debra T. Silverman, Stephen J. Chanock, Xifeng Wu

Research output: Contribution to journalArticle

Abstract

Genome-wide and candidate-gene association studies of bladder cancer have identified 10 susceptibility loci thus far. We conducted a meta-analysis of two previously published genome-wide scans (4501 cases and 6076 controls of European background) and followed up the most significant association signals [17 single nucleotide polymorphisms (SNPs) in 10 genomic regions] in 1382 cases and 2201 controls from four studies. A combined analysis adjusted for study center, age, sex, and smoking status identified a novel susceptibility locus that mapped to a region of 18q12.3, marked by rs7238033 (P = 8.7 × 10 -9; allelic odds ratio 1.20 with 95% CI: 1.13-1.28) and two highly correlated SNPs, rs10775480/rs10853535 (r 2= 1.00; P = 8.9 × 10 -9; allelic odds ratio 1.16 with 95% CI: 1.10-1.22). The signal localizes to the solute carrier family 14 member 1 gene, SLC14A1, a urea transporter that regulates cellular osmotic pressure. In the kidney, SLC14A1 regulates urine volume and concentration whereas in erythrocytes it determines the Kidd blood groups. Our findings suggest that genetic variation in SLC14A1 could provide new etiological insights into bladder carcinogenesis. Published by Oxford University Press 2011.

Original languageEnglish (US)
Article numberddr342
Pages (from-to)4282-4289
Number of pages8
JournalHuman Molecular Genetics
Volume20
Issue number21
DOIs
StatePublished - Nov 2011
Externally publishedYes

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Genome-Wide Association Study
Urinary Bladder Neoplasms
Single Nucleotide Polymorphism
Chromosomes
Odds Ratio
Genome
Osmotic Pressure
Genetic Association Studies
Blood Group Antigens
Genes
Meta-Analysis
Carcinogenesis
Urinary Bladder
Erythrocytes
Smoking
Urine
Kidney
urea transporter

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

A genome-wide association study of bladder cancer identifies a new susceptibility locus within SLC14A1, a urea transporter gene on chromosome 18q12.3. / Garcia-closas, Montserrat; Ye, Yuanqing; Rothman, Nathaniel; Figueroa, Jonine D.; Malats, Núria; Dinney, Colin P.; Chatterjee, Nilanjan; Prokunina-olsson, Ludmila; Wang, Zhaoming; Lin, Jie; Real, Francisco X.; Jacobs, Kevin B.; Baris, Dalsu; Thun, Michael; De vivo, Immaculata; Albanes, Demetrius; Purdue, Mark P.; Kogevinas, Manolis; Kamat, Ashish M.; Lerner, Seth P.; Barton grossman, H.; Gu, Jian; Pu, Xia; Hutchinson, Amy; Fu, Yi Ping; Burdett, Laurie; Yeager, Meredith; Tang, Wei; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-closas, Reina; Lloreta, Josep; Johnson, Alison; Schwenn, Molly; Karagas, Margaret R.; Schned, Alan; Andriole, Gerald; Grubb, Robert; Black, Amanda; Jacobs, Eric J.; Ryan diver, W.; Gapstur, Susan M.; Weinstein, Stephanie J.; Virtamo, Jarmo; Hunter, David J.; Caporaso, Neil; Teresa landi, Maria; Fraumeni, Joseph F.; Silverman, Debra T.; Chanock, Stephen J.; Wu, Xifeng.

In: Human Molecular Genetics, Vol. 20, No. 21, ddr342, 11.2011, p. 4282-4289.

Research output: Contribution to journalArticle

Garcia-closas, M, Ye, Y, Rothman, N, Figueroa, JD, Malats, N, Dinney, CP, Chatterjee, N, Prokunina-olsson, L, Wang, Z, Lin, J, Real, FX, Jacobs, KB, Baris, D, Thun, M, De vivo, I, Albanes, D, Purdue, MP, Kogevinas, M, Kamat, AM, Lerner, SP, Barton grossman, H, Gu, J, Pu, X, Hutchinson, A, Fu, YP, Burdett, L, Yeager, M, Tang, W, Tardón, A, Serra, C, Carrato, A, García-closas, R, Lloreta, J, Johnson, A, Schwenn, M, Karagas, MR, Schned, A, Andriole, G, Grubb, R, Black, A, Jacobs, EJ, Ryan diver, W, Gapstur, SM, Weinstein, SJ, Virtamo, J, Hunter, DJ, Caporaso, N, Teresa landi, M, Fraumeni, JF, Silverman, DT, Chanock, SJ & Wu, X 2011, 'A genome-wide association study of bladder cancer identifies a new susceptibility locus within SLC14A1, a urea transporter gene on chromosome 18q12.3', Human Molecular Genetics, vol. 20, no. 21, ddr342, pp. 4282-4289. https://doi.org/10.1093/hmg/ddr342
Garcia-closas, Montserrat ; Ye, Yuanqing ; Rothman, Nathaniel ; Figueroa, Jonine D. ; Malats, Núria ; Dinney, Colin P. ; Chatterjee, Nilanjan ; Prokunina-olsson, Ludmila ; Wang, Zhaoming ; Lin, Jie ; Real, Francisco X. ; Jacobs, Kevin B. ; Baris, Dalsu ; Thun, Michael ; De vivo, Immaculata ; Albanes, Demetrius ; Purdue, Mark P. ; Kogevinas, Manolis ; Kamat, Ashish M. ; Lerner, Seth P. ; Barton grossman, H. ; Gu, Jian ; Pu, Xia ; Hutchinson, Amy ; Fu, Yi Ping ; Burdett, Laurie ; Yeager, Meredith ; Tang, Wei ; Tardón, Adonina ; Serra, Consol ; Carrato, Alfredo ; García-closas, Reina ; Lloreta, Josep ; Johnson, Alison ; Schwenn, Molly ; Karagas, Margaret R. ; Schned, Alan ; Andriole, Gerald ; Grubb, Robert ; Black, Amanda ; Jacobs, Eric J. ; Ryan diver, W. ; Gapstur, Susan M. ; Weinstein, Stephanie J. ; Virtamo, Jarmo ; Hunter, David J. ; Caporaso, Neil ; Teresa landi, Maria ; Fraumeni, Joseph F. ; Silverman, Debra T. ; Chanock, Stephen J. ; Wu, Xifeng. / A genome-wide association study of bladder cancer identifies a new susceptibility locus within SLC14A1, a urea transporter gene on chromosome 18q12.3. In: Human Molecular Genetics. 2011 ; Vol. 20, No. 21. pp. 4282-4289.
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abstract = "Genome-wide and candidate-gene association studies of bladder cancer have identified 10 susceptibility loci thus far. We conducted a meta-analysis of two previously published genome-wide scans (4501 cases and 6076 controls of European background) and followed up the most significant association signals [17 single nucleotide polymorphisms (SNPs) in 10 genomic regions] in 1382 cases and 2201 controls from four studies. A combined analysis adjusted for study center, age, sex, and smoking status identified a novel susceptibility locus that mapped to a region of 18q12.3, marked by rs7238033 (P = 8.7 × 10 -9; allelic odds ratio 1.20 with 95{\%} CI: 1.13-1.28) and two highly correlated SNPs, rs10775480/rs10853535 (r 2= 1.00; P = 8.9 × 10 -9; allelic odds ratio 1.16 with 95{\%} CI: 1.10-1.22). The signal localizes to the solute carrier family 14 member 1 gene, SLC14A1, a urea transporter that regulates cellular osmotic pressure. In the kidney, SLC14A1 regulates urine volume and concentration whereas in erythrocytes it determines the Kidd blood groups. Our findings suggest that genetic variation in SLC14A1 could provide new etiological insights into bladder carcinogenesis. Published by Oxford University Press 2011.",
author = "Montserrat Garcia-closas and Yuanqing Ye and Nathaniel Rothman and Figueroa, {Jonine D.} and N{\'u}ria Malats and Dinney, {Colin P.} and Nilanjan Chatterjee and Ludmila Prokunina-olsson and Zhaoming Wang and Jie Lin and Real, {Francisco X.} and Jacobs, {Kevin B.} and Dalsu Baris and Michael Thun and {De vivo}, Immaculata and Demetrius Albanes and Purdue, {Mark P.} and Manolis Kogevinas and Kamat, {Ashish M.} and Lerner, {Seth P.} and {Barton grossman}, H. and Jian Gu and Xia Pu and Amy Hutchinson and Fu, {Yi Ping} and Laurie Burdett and Meredith Yeager and Wei Tang and Adonina Tard{\'o}n and Consol Serra and Alfredo Carrato and Reina Garc{\'i}a-closas and Josep Lloreta and Alison Johnson and Molly Schwenn and Karagas, {Margaret R.} and Alan Schned and Gerald Andriole and Robert Grubb and Amanda Black and Jacobs, {Eric J.} and {Ryan diver}, W. and Gapstur, {Susan M.} and Weinstein, {Stephanie J.} and Jarmo Virtamo and Hunter, {David J.} and Neil Caporaso and {Teresa landi}, Maria and Fraumeni, {Joseph F.} and Silverman, {Debra T.} and Chanock, {Stephen J.} and Xifeng Wu",
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AU - Garcia-closas, Montserrat

AU - Ye, Yuanqing

AU - Rothman, Nathaniel

AU - Figueroa, Jonine D.

AU - Malats, Núria

AU - Dinney, Colin P.

AU - Chatterjee, Nilanjan

AU - Prokunina-olsson, Ludmila

AU - Wang, Zhaoming

AU - Lin, Jie

AU - Real, Francisco X.

AU - Jacobs, Kevin B.

AU - Baris, Dalsu

AU - Thun, Michael

AU - De vivo, Immaculata

AU - Albanes, Demetrius

AU - Purdue, Mark P.

AU - Kogevinas, Manolis

AU - Kamat, Ashish M.

AU - Lerner, Seth P.

AU - Barton grossman, H.

AU - Gu, Jian

AU - Pu, Xia

AU - Hutchinson, Amy

AU - Fu, Yi Ping

AU - Burdett, Laurie

AU - Yeager, Meredith

AU - Tang, Wei

AU - Tardón, Adonina

AU - Serra, Consol

AU - Carrato, Alfredo

AU - García-closas, Reina

AU - Lloreta, Josep

AU - Johnson, Alison

AU - Schwenn, Molly

AU - Karagas, Margaret R.

AU - Schned, Alan

AU - Andriole, Gerald

AU - Grubb, Robert

AU - Black, Amanda

AU - Jacobs, Eric J.

AU - Ryan diver, W.

AU - Gapstur, Susan M.

AU - Weinstein, Stephanie J.

AU - Virtamo, Jarmo

AU - Hunter, David J.

AU - Caporaso, Neil

AU - Teresa landi, Maria

AU - Fraumeni, Joseph F.

AU - Silverman, Debra T.

AU - Chanock, Stephen J.

AU - Wu, Xifeng

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