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Genome-wide association study identifies multiple loci associated with bladder cancer risk.


ABSTRACT: Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10(-5) was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10(-9)) and rs907611 on 11p15.5 (P = 4.11 × 10(-8)). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10(-7)) and rs4510656 on 6p22.3 (P = 6.98 × 10(-7)); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.

SUBMITTER: Figueroa JD 

PROVIDER: S-EPMC3919005 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Genome-wide association study identifies multiple loci associated with bladder cancer risk.

Figueroa Jonine D JD   Ye Yuanqing Y   Siddiq Afshan A   Garcia-Closas Montserrat M   Chatterjee Nilanjan N   Prokunina-Olsson Ludmila L   Cortessis Victoria K VK   Kooperberg Charles C   Cussenot Olivier O   Benhamou Simone S   Prescott Jennifer J   Porru Stefano S   Dinney Colin P CP   Malats Núria N   Baris Dalsu D   Purdue Mark M   Jacobs Eric J EJ   Albanes Demetrius D   Wang Zhaoming Z   Deng Xiang X   Chung Charles C CC   Tang Wei W   Bas Bueno-de-Mesquita H H   Trichopoulos Dimitrios D   Ljungberg Börje B   Clavel-Chapelon Françoise F   Weiderpass Elisabete E   Krogh Vittorio V   Dorronsoro Miren M   Travis Ruth R   Tjønneland Anne A   Brenan Paul P   Chang-Claude Jenny J   Riboli Elio E   Conti David D   Gago-Dominguez Manuela M   Stern Mariana C MC   Pike Malcolm C MC   Van Den Berg David D   Yuan Jian-Min JM   Hohensee Chancellor C   Rodabough Rebecca R   Cancel-Tassin Geraldine G   Roupret Morgan M   Comperat Eva E   Chen Constance C   De Vivo Immaculata I   Giovannucci Edward E   Hunter David J DJ   Kraft Peter P   Lindstrom Sara S   Carta Angela A   Pavanello Sofia S   Arici Cecilia C   Mastrangelo Giuseppe G   Kamat Ashish M AM   Lerner Seth P SP   Barton Grossman H H   Lin Jie J   Gu Jian J   Pu Xia X   Hutchinson Amy A   Burdette Laurie L   Wheeler William W   Kogevinas Manolis M   Tardón Adonina A   Serra Consol C   Carrato Alfredo A   García-Closas Reina R   Lloreta Josep J   Schwenn Molly M   Karagas Margaret R MR   Johnson Alison A   Schned Alan A   Armenti Karla R KR   Hosain G M GM   Andriole Gerald G   Grubb Robert R   Black Amanda A   Ryan Diver W W   Gapstur Susan M SM   Weinstein Stephanie J SJ   Virtamo Jarmo J   Haiman Chris A CA   Landi Maria T MT   Caporaso Neil N   Fraumeni Joseph F JF   Vineis Paolo P   Wu Xifeng X   Silverman Debra T DT   Chanock Stephen S   Rothman Nathaniel N  

Human molecular genetics 20131024 5


Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P <  ...[more]

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