A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

Rothman, N; Garcia-Closas, M; Chatterjee, N; Malats, N; Wu, X; Figueroa, JD; Real, FX; Van Den Berg, D; Matullo, G; Baris, D; Thun, M; Kiemeney, LA; Vineis, P; De Vivo, I; Albanes, D; Purdue, MP; Rafnar, T; Hildebrandt, MA; Kiltie, AE; Cussenot, O; Golka, K; Kumar, R; Taylor, JA; Mayordomo, JI; Jacobs, KB; Kogevinas, M; Hutchinson, A; Wang, Z; Fu, YP; Prokunina-Olsson, L; Burdett, L; Yeager, M; Wheeler, W; Tardón, A; Serra, C; Carrato, A; García-Closas, R; Lloreta, J; Johnson, A; Schwenn, M; Karagas, MR; Schned, A; Andriole, G. Andriole G Jr, Grubb R 3rd, Black A, Jacobs, EJ; Diver, WR; Gapstur, SM; Weinstein, SJ; Virtamo, J; Cortessis, VK; Gago-Dominguez, M; Pike, MC; Stern, MC; Yuan, JM; Hunter, DJ; McGrath, M; Dinney, CP; Czerniak, B; Chen, M; Yang, H; Vermeulen, SH; Aben, KK; Witjes, JA; Makkinje, RR; Sulem, P; Besenbacher, S; Stefansson, K; Riboli, E; Brennan, P; Panico, S; Navarro, C; Allen, NE; Bueno-de-Mesquita, HB; Trichopoulos, D; Caporaso, N; Landi, MT; Canzian, F; Ljungberg, B; Tjonneland, A; Clavel-Chapelon, F; Bishop, DT; Teo, MT; Knowles, MA; Guarrera, S; Polidoro, S; Ricceri, F; Sacerdote, C; Allione, A; Cancel-Tassin, G; Selinski, S; Hengstler, JG; Dietrich, H; Fletcher, T; Rudnai, P; Gurzau, E; Koppova, K; Bolick, SC; Godfrey, A; Xu, Z; Sanz-Velez, JI; D García-Prats, M; Sanchez, M; Valdivia, G; Porru, S; Benhamou, S; Hoover, RN; Fraumeni, JFJr; Silverman, DT; Chanock, SJ; (2010) A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci. Nature genetics, 42 (11). pp. 978-84. ISSN 1061-4036 DOI: https://doi.org/10.1038/ng.687

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We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10?¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10?¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10??) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10?¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10?¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis.

Item Type: Article
Faculty and Department: Faculty of Public Health and Policy > Dept of Social and Environmental Health Research
PubMed ID: 20972438
Web of Science ID: 283540500015
URI: http://researchonline.lshtm.ac.uk/id/eprint/1615


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