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

  1. Author:
    Garcia-Closas, M.
    Ye, Y. Q.
    Rothman, N.
    Figueroa, J. D.
    Malats, N.
    Dinney, C. P.
    Chatterjee, N.
    Prokunina-Olsson, L.
    Wang, Z. M.
    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.
    Lerner, S. P.
    Grossman, H. B.
    Gu, J.
    Pu, X.
    Hutchinson, A.
    Fu, Y. P.
    Burdett, L.
    Yeager, M.
    Tang, W.
    Tardon, A.
    Serra, C.
    Carrato, A.
    Garcia-Closas, R.
    Lloreta, J.
    Johnson, A.
    Schwenn, M.
    Karagas, M. R.
    Schned, A.
    Andriole, G.
    Grubb, R.
    Black, A.
    Jacobs, E. J.
    Diver, W. R.
    Gapstur, S. M.
    Weinstein, S. J.
    Virtamo, J.
    Hunter, D. J.
    Caporaso, N.
    Landi, M. T.
    Fraumeni, J. F.
    Silverman, D. T.
    Chanock, S. J.
    Wu, X. F.

  2. Author Address

    [Garcia-Closas, M; Rothman, N; Figueroa, JD; Chatterjee, N; Prokunina-Olsson, L; Baris, D; Albanes, D; Purdue, MP; Fu, YP; Tang, W; Black, A; Weinstein, SJ; Caporaso, N; Landi, MT; Fraumeni, JF; Silverman, DT; Chanock, SJ] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Garcia-Closas, M] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England. [Ye, YQ; Lin, J; Gu, J; Pu, X; Wu, XF] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Malats, N; Real, FX] Spanish Natl Canc Res Ctr, Madrid, Spain. [Dinney, CP; Kamat, AM; Grossman, HB] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA. [Wang, ZM; Jacobs, KB; Hutchinson, A; Burdett, L; Yeager, M] SAIC Frederick Inc, Core Genotype Facil, Natl Canc Inst Frederick, Frederick, MD USA. [Real, FX; Serra, C; Lloreta, J] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain. [Thun, M; Jacobs, EJ; Diver, WR; Gapstur, SM] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [De Vivo, I] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Kogevinas, M] Ctr Recerca Epidemiol Ambiental CREAL, Barcelona, Spain. [Kogevinas, M; Lloreta, J] Parc Salut Mar Inst Municipal Invest Med IMIM, Barcelona, Spain. [Kogevinas, M; Tardon, A] CIBER Epidemio & Salud Publ CIBERESP, Barcelona, Spain. [Kogevinas, M] Natl Sch Publ Hlth, Athens, Greece. [Lerner, SP] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. [Tardon, A] Univ Oviedo, Oviedo, Spain. [Carrato, A] Ramon & Cajal Univ Hosp, Madrid, Spain. [Garcia-Closas, R] Hosp Univ Canarias, Unidad Invest, San Cristobal la Laguna, Spain. [Johnson, A] Vermont Canc Registry, Burlington, VT USA. [Schwenn, M] Maine Canc Registry, Augusta, ME USA. [Karagas, MR] Dartmouth Coll, Hanover, NH 03755 USA. [Andriole, G; Grubb, R] Washington Univ, Sch Med, Dept Urol, St Louis, MO USA. [Schned, A; Virtamo, J] Natl Inst Hlth & Welf, Helsinki, Finland. [Hunter, DJ] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.;Garcia-Closas, M (reprint author), Inst Canc Res, Epidemiol Sect, 15 Cotswold Rd, Sutton SM2 5NG, Surrey, England;montse.garciaclosas@icr.ac.uk
    1. Year: 2011
    2. Date: Nov
  2. Journal: Human Molecular Genetics
    1. 20
    2. 21
    3. Pages: 4282-4289
  4. Type of Article: Article
  5. ISSN: 0964-6906
  1. 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 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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  2. DOI: 10.1093/hmg/ddr342
  3. View record in Web of Science®
  4. WOS: 000295686000017

Library Notes

  1. Fiscal Year: FY2011-2012
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