Dataset Information

Cancer Genetic Markers of Susceptibility for Bladder Cancer (CGEMS Bladder)

ABSTRACT:

This study funded by the National Cancer Institute (NCI) involves conducting a genome-wide association study of common genetic variants to identify markers of susceptibility to bladder cancer.

This bladder GWAS has led to the discovery of three novel regions in the genome associated with bladder cancer risk. Cases were defined as individuals having histologically confirmed primary carcinoma of the urinary bladder, including carcinoma in situ (ICD-0-2 topography codes C67.0-C67.9 or ICD9 codes 188.1-188.9). Scan data were obtained from two case-control studies carried out in Spain and the United States (specifically, those in the Maine and Vermont components of the New England Bladder Cancer Study) and three prospective cohort studies in Finland and the United States (specifically Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, and The American Cancer Society Cancer Prevention Study II Nutrition Cohort).

We used data from 591,637 single nucleotide polymorphisms 3,532 affected individuals (cases) and 5,119 controls of European descent and replication including 8382 cases and 48275 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 x 10^-12) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 x 10^-11) on maps to CCNE1 and rs11892031 (P = 1 x 10^-7) 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 (Rothman N et al., Nature Genetics, 2010, PMID: 20972438). Through meta-analysis with the MD Anderson Texas Bladder Cancer Study (TXBCS), we also identified a novel susceptibility locus that mapped to a region of 18q12.3, marked by rs7238033 (P = 8.7 x 10(-9); allelic odds ratio 1.20 with 95% CI: 1.13-1.28) and two highly correlated SNPs, rs10775480/rs10853535 (r(2)= 1.00; P = 8.9 x 10(-9); allelic odds ratio 1.16 with 95% CI: 1.10-1.22) (Garcia-Closas M et al, Human Molecular Genetics, 2011)

For NCI-GWAS2, we performed genotyping on cases and controls for the New Hampshire component of the New England Bladder Cancer Study (NEBCS-NH). For the majority of new bladder cancer cases, we genotyped only cases from four case-control studies, the Los Angeles Bladder Cancer Study (LABCS), the French Center for Research on Prostate Diseases (CeRePP), the French Bladder Study (FBCS) and the Brescia Bladder Cancer Study (BBCS). We used existing control data from four cohort studies already genotyped and subjected to rigorous quality control metrics: the European Prospective Investigation Into Cancer and Nutrition Study (EPIC), Womens Health Initiative (WHI), Health Professionals Follow-up Study (HPFS), Nurses Health Study (NHS), which have been a part of Cancer Genetic Markers of Susceptibility (CGEMS).

Meta-analysis of NCI-GWAS1, NCI-GWAS2 and a previously reported GWAS TXBCS-GWAS along with taqman replication, identified two new loci: rs10936599 on 3q26.2 (P = 4.53 x 10(-9)) and rs907611 on 11p15.5 (P = 4.11 x 10(-8)). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 x 10(-7)) and rs4510656 on 6p22.3 (P = 6.98 X 10(-7)); these require further studies for confirmation (Figueroa J et al, Human Molecular Genetics, 2013).

PROVIDER: phs000346 | dbGaP |

SECONDARY ACCESSION(S): PRJNA75811PRJNA75809

REPOSITORIES: dbGaP

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	GapExchange_phs000346.v1.p1.xml	Xml
	dbGaPEx2.1.5.xsd	Other
	phs000346.v1-Documents.zip	Other
	Study_Report.phs000346.CGEMS_BladderCancer_Rothman.v1.p1.MULTI.pdf	Pdf
	manifest_phs000346.CGEMS_BladderCancer_Rothman.v1.p1.c1.CADM.pdf	Pdf

Items per page:

1 - 5 of 30

Similar Datasets

Project description:Within the framework of the NCI-sponsored Cohort Consortium, investigators from 12 prospective epidemiologic cohorts formed the Pancreatic Cancer Cohort Consortium in 2006. This study, also known as "PanScan", is funded by the National Cancer Institute (NCI) and involves conducting a genome-wide association study of common genetic variants to identify markers of susceptibility to pancreatic cancer. In 2007, the study expanded to include 8 case-controls studies. The study team includes scientists from the cohorts comprising the Consortium and NCI and from the PanC4 case-control studies. The PanScan consortium has conducted two GWAS that have led to the discovery of four novel regions in the genome associated with risk for pancreatic adenocarcinoma. The first two scans were conducted in 12 cohort studies and 8 case-control studies. Initially, we genotyped 523,345 single nucleotide polymorphisms in 1,528 incident cases and 1,594 controls from nested case-control studies of 12 cohorts plus 368 cases and 345 controls from one hospital-based case-control study. Taqman replication of SNPs from the three most promising regions in the initial scan, as determined by rank p-values, was done in 2,457 cases and 2,654 controls from eight case-control studies that were part of the PanC4 consortium. A combined analysis identified an association between a locus on 9q34 and pancreatic cancer, the single nucleotide polymorphism rs505922 (P= 5.37 x 10-8; multiplicative per-allele odds ratio (OR) 1.20; 95% CI 1.12-1.28), which maps to the first intron of the ABO blood group gene whose protein determines an individual's blood group (Amundadottir et al, Nature Genetics 2009, PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/19648918" target="_blank">19648918</a>). In PanScan 2, we conducted a combined analysis of 3,851 pancreatic cancer cases and 3,934 controls. These included 1896 cases and 1939 controls that were scanned in PanScan1 (above) and 1955 cases and 1995 controls that were newly scanned in PanScan2. The second GWAS did not include 502 cases and 659 controls that were part of the rapid replication. (Please see the attached table for the total number of subjects who were GWASed and included in PanScan1 and PanScan2). Three new regions were identified: chromosome 13q22.1 (rs9543325; P=3.27 x 10-11; per-allele odds ratio (OR) 1.26; 95% CI 1.18-1.35); chromosome 1q32.1 in the NR5A2 gene (rs3790844; P=2.45 x 10-10; per-allele OR 0.77; 95% CI 0.71-0.84); and chromosome 5p15.33 (rs401681 in the CLPTM1L and TERT region; P=3.66 x 10-7; per-allele OR 1.19; 95% CI 1.11-1.27). The first two regions have not been identified in GWAS of cancer to date but the last region has been reported to be associated with risk of other malignancies (Petersen et al, Nature Genetics 2010, PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/20101243" target="_blank">20101243</a>).

Dataset Information

Cancer Genetic Markers of Susceptibility for Bladder Cancer (CGEMS Bladder)

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets