NCI Bladder GWAS
Principal Investigator
Name
Stella Koutros
Degrees
PhD, MPH
Institution
National Cancer Institute
Position Title
Investigator
Email
About this CDAS Project
Study
PLCO
(Learn more about this study)
Project ID
PLCO-957
Initial CDAS Request Approval
Mar 30, 2022
Title
NCI Bladder GWAS
Summary
Previous genome-wide association studies (GWAS) have identified over a dozen loci associated with bladder cancer risk in individuals of European ancestry. Some of these loci lie near or within genes related to carcinogen metabolism (NAT2, UGT1A6, GSTM1), DNA maintenance (TERC, TERT-CLPTML1), and oncogenes or tumor suppressors (CCNE1, TP63, FGFR3). Follow-up studies of GWAS regions, namely, PSCA, UGT1A6, CCNE1, SLC14A1, and APOBEC3B, have yielded important insights into the underlying molecular mechanisms. The known bladder cancer susceptibility loci are estimated to explain approximately 12% of the familial risk of bladder cancer; further estimates of heritability suggest more loci are yet to be identified. We aim to conduct a meta-analysis of genome-wide genotype to identify novel susceptibility loci and evaluate their interactions with smoking. Thus, we are requesting genetic data from the PLCO Atlas study population. As part of previous bladder GWAS efforts, some bladder cancer cases have already been included (using older array data). As a result, we will need to cross check those PLCO subjects already included in our analyses with the newest genotyping data/subject information. We will need to identify ‘new’ incident bladder cancer cases and non-cases (free of other cancers before, during the follow-up period) and use associated subject level information including: age, sex, smoking status as well as stage and grade information for cancer cases.
Aims
-Conduct a meta-analysis of genome-wide genotype to identify novel susceptibility loci for bladder cancer
-Conduct analyses stratified by sex, smoking status (and their interactions)
-Conduct subtype analyses based on non-muscle invasive (low and high grade)/muscle-invasive status
Collaborators
Nathaniel Rothman NCI/DCEG
Debra Silverman NCI/DCEG
Ludmila Prokunina Olsson NCI/DCEG
Oscar Florez-Vargas NCI/DCEG
Related Publications
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Genome-wide Association Study of Bladder Cancer Reveals New Biological and Translational Insights.
Koutros S, Kiemeney LA, Pal Choudhury P, Milne RL, Lopez de Maturana E, Ye Y, Joseph V, Florez-Vargas O, Dyrskjøt L, Figueroa J, Dutta D, Giles GG, Hildebrandt MAT, Offit K, Kogevinas M, Weiderpass E, McCullough ML, Freedman ND, Albanes D, Kooperberg C, ...show more Cortessis VK, Karagas MR, Johnson A, Schwenn MR, Baris D, Furberg H, Bajorin DF, Cussenot O, Cancel-Tassin G, Benhamou S, Kraft P, Porru S, Carta A, Bishop T, Southey MC, Matullo G, Fletcher T, Kumar R, Taylor JA, Lamy P, Prip F, Kalisz M, Weinstein SJ, Hengstler JG, Selinski S, Harland M, Teo M, Kiltie AE, Tardón A, Serra C, Carrato A, García-Closas R, Lloreta J, Schned A, Lenz P, Riboli E, Brennan P, Tjønneland A, Otto T, Ovsiannikov D, Volkert F, Vermeulen SH, Aben KK, Galesloot TE, Turman C, De Vivo I, Giovannucci E, Hunter DJ, Hohensee C, Hunt R, Patel AV, Huang WY, Thorleifsson G, Gago-Dominguez M, Amiano P, Golka K, Stern MC, UROMOL Consortium, Yan W, Liu J, Li SA, Katta S, Hutchinson A, Hicks B, Wheeler WA, Purdue MP, McGlynn KA, Kitahara CM, Haiman CA, Greene MH, Rafnar T, Chatterjee N, Chanock SJ, Wu X, Real FX, Silverman DT, Garcia-Closas M, Stefansson K, Prokunina-Olsson L, Malats N, Rothman N
Eur Urol. 2023 May 18 PUBMED