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GWAS Study

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 M, Ye Y, Rothman N et al.

21824976 PubMed ID
GWAS Study Type
14160 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

GM
Garcia-Closas M
YY
Ye Y
RN
Rothman N
FJ
Figueroa JD
MN
Malats N
DC
Dinney CP
CN
Chatterjee N
PL
Prokunina-Olsson L
WZ
Wang Z
LJ
Lin J
RF
Real FX
JK
Jacobs KB
BD
Baris D
TM
Thun M
DV
De Vivo I
AD
Albanes D
PM
Purdue MP
KM
Kogevinas M
KA
Kamat AM
LS
Lerner SP
GH
Grossman HB
GJ
Gu J
PX
Pu X
HA
Hutchinson A
FY
Fu YP
BL
Burdett L
YM
Yeager M
TW
Tang W
TA
Tardón A
SC
Serra C
CA
Carrato A
GR
García-Closas R
LJ
Lloreta J
JA
Johnson A
SM
Schwenn M
KM
Karagas MR
SA
Schned A
AG
Andriole G
GR
Grubb R
BA
Black A
JE
Jacobs EJ
DW
Diver WR
GS
Gapstur SM
WS
Weinstein SJ
VJ
Virtamo J
HD
Hunter DJ
CN
Caporaso N
LM
Landi MT
FJ
Fraumeni JF
SD
Silverman DT
CS
Chanock SJ
WX
Wu X
Chapter II

Abstract

Summary of the research findings

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.

4,501 European ancestry cases, 6,076 European ancestry controls

Chapter III

Study Statistics

Key metrics and study information

14160
Total Participants
GWAS
Study Type
Yes
Replicated
1,382 European ancestry cases, 2,201 European ancestry controls
Replication Participants
European
Ancestry
Finland, U.S., Spain
Recruitment Country
Chapter IV

Analysis

Comprehensive review of health and genetic findings

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