Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry
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Banday, A. Rouf
Castelao, Jose Esteban
Martinez, Maria Elena
Bueno-De-Mesquita, H. Bas
Van Den Berg, David
De Vivo, Immaculata
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CitationFigueroa, Jonine D., Candace D. Middlebrooks, A. Rouf Banday, Yuanqing Ye, Montserrat Garcia-Closas, Nilanjan Chatterjee, Stella Koutros, et al. 2016. “Identification of a Novel Susceptibility Locus at 13q34 and Refinement of the 20p12.2 Region as a Multi-Signal Locus Associated with Bladder Cancer Risk in Individuals of European Ancestry.” Human Molecular Genetics 25 (6): 1203–14. https://doi.org/10.1093/hmg/ddv492.
AbstractCandidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1x 10(-6)), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 x 10(-11)) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 x 10(-10)). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region-the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r(2) = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case-case P <= 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer.
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