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. Lerner; H. 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

doi:10.1093/hmg/ddr342

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

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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.

Original language	English
Article number	ddr342
Pages (from-to)	4282-4289
Number of pages	8
Journal	Human molecular genetics
Volume	20
Issue number	21
DOIs	https://doi.org/10.1093/hmg/ddr342
State	Published - Nov 2011

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10.1093/hmg/ddr342

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Garcia-closas, M., Ye, Y., Rothman, N., Figueroa, J. D., Malats, N., Dinney, C. P., Chatterjee, N., Prokunina-olsson, L., Wang, Z., Lin, J., Real, F. X., Jacobs, K. B., Baris, D., Thun, M., De vivo, I., Albanes, D., Purdue, M. P., Kogevinas, M., Kamat, A. M., ... 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, 20(21), 4282-4289. Article ddr342. https://doi.org/10.1093/hmg/ddr342

@article{1247a3f6a678412eacf0a816cef0616f,

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

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",

note = "Funding Information: SBCS (D.T.S., N.R., S.J.C., M.G.C.)—Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics and intramural contract number NCI N02-CP-11015. FIS/Spain 98/1274, FIS/Spain 00/0745, PI061614 and G03/174, Funda-ci{\'o} Marat{\'o} TV3, Red Tem{\'a}tica Investigaci{\'o}n Cooperativa en C{\'a}ncer (RTICC), Consol{\'i}der ONCOBIO, EU-FP7-201663; and RO1-CA089715 and CA34627. Funding Information: The NCI bladder cancer GWAS was supported by the intramural research program of the National Institutes of Health, National Cancer Institute. This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Funding Information: PLCO (M.P.P)—the NIH Genes, Environment and Health Initiative (GEI) partly funded DNA extraction and statistical analyses (HG-06-033-NCI-01 and RO1HL091172-01), geno-typing at the Johns Hopkins University Center for Inherited Disease Research (U01HG004438 and NIH HHSN26820 0782096C) and study coordination at the GENEVA (N.C.)— The NIH Genes, Environment and Health Initiative (GEI) partly funded DNA extraction and statistical analyses (HG-06-033-NCI-01 and RO1HL091172-01), genotyping at the Johns Hopkins University Center for Inherited Disease Research (U01HG004438 and NIH HHSN268200782096C) and study coordination at the GENEVA Coordination Center (U01 HG004446) for EAGLE and part of PLCO studies. Genotyping for the remaining part of PLCO and all ATBC and CPS-II samples were supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. Funding Information: ATBC (D.A.)—this research was supported in part by the Intramural Research Program of the NIH and the National Cancer Institute. Additionally, this research was supported by U.S. Public Health Service contracts N01-CN-45165, N01-RC-45035 and N01-RC-37004 from the National Cancer Institute, Department of Health and Human Services. Funding Information: NEBCS (D.T.S.)—Intramural research program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics and intramural contract number NCI N02-CP-01037.",

year = "2011",

month = nov,

doi = "10.1093/hmg/ddr342",

language = "English",

volume = "20",

pages = "4282--4289",

journal = "Human molecular genetics",

issn = "0964-6906",

number = "21",

}

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

TY - JOUR

T1 - A genome-wide association study of bladder cancer identifies a new susceptibility locus within SLC14A1, a urea transporter gene on chromosome 18q12.3

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

N1 - Funding Information: SBCS (D.T.S., N.R., S.J.C., M.G.C.)—Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics and intramural contract number NCI N02-CP-11015. FIS/Spain 98/1274, FIS/Spain 00/0745, PI061614 and G03/174, Funda-ció Marató TV3, Red Temática Investigación Cooperativa en Cáncer (RTICC), Consolíder ONCOBIO, EU-FP7-201663; and RO1-CA089715 and CA34627. Funding Information: The NCI bladder cancer GWAS was supported by the intramural research program of the National Institutes of Health, National Cancer Institute. This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Funding Information: PLCO (M.P.P)—the NIH Genes, Environment and Health Initiative (GEI) partly funded DNA extraction and statistical analyses (HG-06-033-NCI-01 and RO1HL091172-01), geno-typing at the Johns Hopkins University Center for Inherited Disease Research (U01HG004438 and NIH HHSN26820 0782096C) and study coordination at the GENEVA (N.C.)— The NIH Genes, Environment and Health Initiative (GEI) partly funded DNA extraction and statistical analyses (HG-06-033-NCI-01 and RO1HL091172-01), genotyping at the Johns Hopkins University Center for Inherited Disease Research (U01HG004438 and NIH HHSN268200782096C) and study coordination at the GENEVA Coordination Center (U01 HG004446) for EAGLE and part of PLCO studies. Genotyping for the remaining part of PLCO and all ATBC and CPS-II samples were supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. Funding Information: ATBC (D.A.)—this research was supported in part by the Intramural Research Program of the NIH and the National Cancer Institute. Additionally, this research was supported by U.S. Public Health Service contracts N01-CN-45165, N01-RC-45035 and N01-RC-37004 from the National Cancer Institute, Department of Health and Human Services. Funding Information: NEBCS (D.T.S.)—Intramural research program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics and intramural contract number NCI N02-CP-01037.

PY - 2011/11

Y1 - 2011/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80053958730&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddr342

DO - 10.1093/hmg/ddr342

M3 - Article

C2 - 21824976

AN - SCOPUS:80053958730

SN - 0964-6906

VL - 20

SP - 4282

EP - 4289

JO - Human molecular genetics

JF - Human molecular genetics

IS - 21

M1 - ddr342

ER -

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

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