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Grant Details

Grant Number: 1U01CA155309-01A1 Interpret this number
Primary Investigator: Scelo, Ghislaine
Organization: International Agency For Res On Cancer
Project Title: Pooled Genome-Wide Analysis of Kidney Cancer Risk
Fiscal Year: 2011


Abstract

DESCRIPTION (provided by applicant): Renal cell carcinoma (RCC) is the 8th most common cancer in the US and the 10th most common form of cancer death, with over 34,000 cases and 12,000 deaths each year. A sharp increase in the incidence of RCC was observed in recent decades with some of the greatest increases happening in Central Europe and among the black population in the US. Apart from smoking, obesity and hypertension, much of the etiology of this disease remains to be identified. There is increasing evidence that genetic factors influence susceptibility to RCC, although this hypothesis has been understudied. We have recently completed a genome-wide association study (GWAS) of RCC comprising 3,800 cases and 8,500 controls. We now propose to extend this study by incorporating an additional 3,800 cases and 4,800 controls from a series of population based case-control and cohort studies. Inclusion of cohort studies has been facilitated via the NCI cohort consortium initiative. In addition to its size, our study will be unique in several ways: (1) extensive clinicopathological information and survival of cases will be collected; (2) genome-wide analyses for the association between genetic variants and RCC will be conducted for both disease onset and survival; (3) a comprehensive biorepository of germline DNA and tumor DNA and RNA on at least 2,000 cases will be developed; (4) whole-genome gene expression profiling on fresh renal tissue and tumor tissue will be obtained to complement results obtained from the germline genotyping analyses. PUBLIC HEALTH RELEVANCE: The incidence of kidney cancer has been increasing over the past decades and the disease has a very poor prognosis when diagnosed at an advanced stage (20% of the cases in the US). Apart from smoking, obesity and hypertension, much of the etiology of this disease remains to be identified. We propose to investigate genetic factors associated with kidney cancer onset and survival, looking at the genetic variants across the whole genome, and combining this with gene expression analysis of the tumor tissue.



Publications

Understanding the biological processes of kidney carcinogenesis: an integrative multi-omics approach.
Authors: Cortez Cardoso Penha R. , Sexton Oates A. , Senkin S. , Park H.A. , Atkins J. , Holcatova I. , Hornakova A. , Savic S. , Ognjanovic S. , Świątkowska B. , et al. .
Source: Molecular Systems Biology, 2024 Dec; 20(12), p. 1282-1302.
EPub date: 2024-11-26 00:00:00.0.
PMID: 39592856
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Clinical characteristics and HLA associations of azithromycin-induced liver injury.
Authors: Conlon C. , Li Y.J. , Ahmad J. , Barnhart H. , Fontana R.J. , Ghabril M. , Hayashi P.H. , Kleiner D.E. , Lee W.M. , Navarro V. , et al. .
Source: Alimentary Pharmacology & Therapeutics, 2024 Sep; 60(6), p. 787-795.
EPub date: 2024-07-10 00:00:00.0.
PMID: 38988034
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Identification of Reduced ERAP2 Expression and a Novel HLA Allele as Components of a Risk Score for Susceptibility to Liver Injury Due to Amoxicillin-Clavulanate.
Authors: Nicoletti P. , Dellinger A. , Li Y.J. , Barnhart H.X. , Chalasani N. , Fontana R.J. , Odin J.A. , Serrano J. , Stolz A. , Etheridge A.S. , et al. .
Source: Gastroenterology, 2023 Mar; 164(3), p. 454-466.
EPub date: 2022-12-07 00:00:00.0.
PMID: 36496055
Related Citations

Clinical features, outcomes, and HLA risk factors associated with nitrofurantoin-induced liver injury.
Authors: Chalasani N. , Li Y.J. , Dellinger A. , Navarro V. , Bonkovsky H. , Fontana R.J. , Gu J. , Barnhart H. , Phillips E. , Lammert C. , et al. .
Source: Journal Of Hepatology, 2023 Feb; 78(2), p. 293-300.
EPub date: 2022-09-22 00:00:00.0.
PMID: 36152763
Related Citations

Different Pigmentation Risk Loci for High-Risk Monosomy 3 and Low-Risk Disomy 3 Uveal Melanomas.
Authors: Mobuchon L. , Derrien A.C. , Houy A. , Verrier T. , Pierron G. , Cassoux N. , Milder M. , Deleuze J.F. , Boland A. , Scelo G. , et al. .
Source: Journal Of The National Cancer Institute, 2022-02-07 00:00:00.0; 114(2), p. 302-309.
PMID: 34424336
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Sexual dimorphism in cancer: insights from transcriptional signatures in kidney tissue and renal cell carcinoma.
Authors: Laskar R.S. , Li P. , Ecsedi S. , Abedi-Ardekani B. , Durand G. , Robinot N. , Hubert J.N. , Janout V. , Zaridze D. , Mukeria A. , et al. .
Source: Human Molecular Genetics, 2021-04-27 00:00:00.0; 30(5), p. 343-355.
PMID: 33527138
Related Citations

Sex specific associations in genome wide association analysis of renal cell carcinoma.
Authors: Laskar R.S. , Muller D.C. , Li P. , Machiela M.J. , Ye Y. , Gaborieau V. , Foll M. , Hofmann J.N. , Colli L. , Sampson J.N. , et al. .
Source: European Journal Of Human Genetics : Ejhg, 2019-06-23 00:00:00.0; , .
EPub date: 2019-06-23 00:00:00.0.
PMID: 31231134
Related Citations

The influence of obesity-related factors in the etiology of renal cell carcinoma-A mendelian randomization study.
Authors: Johansson M. , Carreras-Torres R. , Scelo G. , Purdue M.P. , Mariosa D. , Muller D.C. , Timpson N.J. , Haycock P.C. , Brown K.M. , Wang Z. , et al. .
Source: Plos Medicine, 2019 01; 16(1), p. e1002724.
EPub date: 2019-01-03 00:00:00.0.
PMID: 30605491
Related Citations

Genome-wide association study identifies multiple risk loci for renal cell carcinoma.
Authors: Scelo G. , Purdue M.P. , Brown K.M. , Johansson M. , Wang Z. , Eckel-Passow J.E. , Ye Y. , Hofmann J.N. , Choi J. , Foll M. , et al. .
Source: Nature Communications, 2017-06-09 00:00:00.0; 8, p. 15724.
EPub date: 2017-06-09 00:00:00.0.
PMID: 28598434
Related Citations

A GWAS in uveal melanoma identifies risk polymorphisms in the CLPTM1L locus.
Authors: Mobuchon L. , Battistella A. , Bardel C. , Scelo G. , Renoud A. , Houy A. , Cassoux N. , Milder M. , Cancel-Tassin G. , Cussenot O. , et al. .
Source: Npj Genomic Medicine, 2017; 2, .
EPub date: 2017-03-10 00:00:00.0.
PMID: 28781888
Related Citations

Aristolochic acid exposure in Romania and implications for renal cell carcinoma.
Authors: Turesky R.J. , Yun B.H. , Brennan P. , Mates D. , Jinga V. , Harnden P. , Banks R.E. , Blanche H. , Bihoreau M.T. , Chopard P. , et al. .
Source: British Journal Of Cancer, 2016-01-12 00:00:00.0; 114(1), p. 76-80.
EPub date: 2016-01-12 00:00:00.0.
PMID: 26657656
Related Citations

Circulating 25-hydroxyvitamin D3 and survival after diagnosis with kidney cancer.
Authors: Muller D.C. , Scelo G. , Zaridze D. , Janout V. , Holcatova I. , Navratilova M. , Mates D. , Midttun Ø. , Ueland P.M. , Brennan P. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2015 Aug; 24(8), p. 1277-81.
PMID: 26021552
Related Citations

Circulating Concentrations of Vitamin B6 and Kidney Cancer Prognosis: A Prospective Case-Cohort Study.
Authors: Muller D.C. , Johansson M. , Zaridze D. , Moukeria A. , Janout V. , Holcatova I. , Navratilova M. , Mates D. , Midttun Ø. , Ueland P.M. , et al. .
Source: Plos One, 2015; 10(10), p. e0140677.
PMID: 26506437
Related Citations

Integrative genome-wide gene expression profiling of clear cell renal cell carcinoma in Czech Republic and in the United States.
Authors: Wozniak M.B. , Le Calvez-Kelm F. , Abedi-Ardekani B. , Byrnes G. , Durand G. , Carreira C. , Michelon J. , Janout V. , Holcatova I. , Foretova L. , et al. .
Source: Plos One, 2013; 8(3), p. e57886.
PMID: 23526956
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