Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
Genome-wide and candidate-gene association studies of bladder cancer have identified ten susceptibility loci thus far. We conducted a meta-analysis of two previously published genome-wide scans (4,501 cases and 6,076 controls of European background) and followed up the most significant association signals (17 SNPs in 10 genomic regions) in 1,382 cases and 2,201 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=8.7x10(-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=8.9x10(-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.
Written by:
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, Grossman HB, 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 Jr, Grubb R 3rd, Black A, Jacobs EJ, Diver WR, Gapstur SM, Weinstein SJ, Virtamo J, Hunter DJ, Caporaso N, Landi MT, Fraumeni JF Jr, Silverman DT, Chanock SJ, Wu X. Are you the author?
Reference: Hum Mol Genet. 2011 Aug 8. Epub ahead of print.
doi: 10.1093/hmg/ddr342
PubMed Abstract
PMID: 21824976
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