Journal
HUMAN MOLECULAR GENETICS
Volume 20, Issue 21, Pages 4282-4289Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddr342
Keywords
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Funding
- National Institutes of Health [HHSN261200800001E, HHSN26820 0782096C]
- National Cancer Institute
- National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics [NCI N02-CP-11015, NCI N02-CP-01037]
- FIS/Spain [98/1274, 00/0745, PI061614, G03/174]
- Fundacio Marato TV3
- Red Tematica Investigacion Cooperativa en Cancer (RTICC)
- Consolider ONCOBIO
- EU [201663, RO1-CA089715, CA34627]
- NIH Genes, Environment and Health Initiative (GEI) [HG-06-033-NCI-01, RO1HL091172-01]
- Johns Hopkins University Center for Inherited Disease Research [U01HG004438]
- Division of Cancer Epidemiology and Genetics
- Division of Cancer Prevention, National Cancer Institute, National Institutes of Health
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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 x 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 x 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.
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