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


ABSTRACT: 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.

SUBMITTER: Rothman N 

PROVIDER: S-EPMC3049891 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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

Rothman Nathaniel N   Garcia-Closas Montserrat M   Chatterjee Nilanjan N   Malats Nuria N   Wu Xifeng X   Figueroa Jonine D JD   Real Francisco X FX   Van Den Berg David D   Matullo Giuseppe G   Baris Dalsu D   Thun Michael M   Kiemeney Lambertus A LA   Vineis Paolo P   De Vivo Immaculata I   Albanes Demetrius D   Purdue Mark P MP   Rafnar Thorunn T   Hildebrandt Michelle A T MA   Kiltie Anne E AE   Cussenot Olivier O   Golka Klaus K   Kumar Rajiv R   Taylor Jack A JA   Mayordomo Jose I JI   Jacobs Kevin B KB   Kogevinas Manolis M   Hutchinson Amy A   Wang Zhaoming Z   Fu Yi-Ping YP   Prokunina-Olsson Ludmila L   Burdett Laurie L   Yeager Meredith M   Wheeler William W   Tardón Adonina A   Serra Consol C   Carrato Alfredo A   García-Closas Reina R   Lloreta Josep J   Johnson Alison A   Schwenn Molly M   Karagas Margaret R MR   Schned Alan A   Andriole Gerald G   Grubb Robert R   Black Amanda A   Jacobs Eric J EJ   Diver W Ryan WR   Gapstur Susan M SM   Weinstein Stephanie J SJ   Virtamo Jarmo J   Cortessis Victoria K VK   Gago-Dominguez Manuela M   Pike Malcolm C MC   Stern Mariana C MC   Yuan Jian-Min JM   Hunter David J DJ   McGrath Monica M   Dinney Colin P CP   Czerniak Bogdan B   Chen Meng M   Yang Hushan H   Vermeulen Sita H SH   Aben Katja K KK   Witjes J Alfred JA   Makkinje Remco R RR   Sulem Patrick P   Besenbacher Soren S   Stefansson Kari K   Riboli Elio E   Brennan Paul P   Panico Salvatore S   Navarro Carmen C   Allen Naomi E NE   Bueno-de-Mesquita H Bas HB   Trichopoulos Dimitrios D   Caporaso Neil N   Landi Maria Teresa MT   Canzian Federico F   Ljungberg Borje B   Tjonneland Anne A   Clavel-Chapelon Francoise F   Bishop David T DT   Teo Mark T W MT   Knowles Margaret A MA   Guarrera Simonetta S   Polidoro Silvia S   Ricceri Fulvio F   Sacerdote Carlotta C   Allione Alessandra A   Cancel-Tassin Geraldine G   Selinski Silvia S   Hengstler Jan G JG   Dietrich Holger H   Fletcher Tony T   Rudnai Peter P   Gurzau Eugen E   Koppova Kvetoslava K   Bolick Sophia C E SC   Godfrey Ashley A   Xu Zongli Z   Sanz-Velez José I JI   D García-Prats María M   Sanchez Manuel M   Valdivia Gabriel G   Porru Stefano S   Benhamou Simone S   Hoover Robert N RN   Fraumeni Joseph F JF   Silverman Debra T DT   Chanock Stephen J SJ  

Nature genetics 20101024 11


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 chromos  ...[more]

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