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Grant Details

Grant Number: 5R03CA099500-02 Interpret this number
Primary Investigator: Andrew, Angeline
Organization: Dartmouth College
Project Title: DNA Repair and Bladder Cancer
Fiscal Year: 2004
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Abstract

DESCRIPTION (provided by applicant): Each year, 51,200 people in the United States are diagnosed with bladder cancer and 10,600 die of the disease. Exposure to environmental chemicals as well as genetic factors play a significant role in initiation of bladder cancer. Epidemiologic investigations have clearly shown an increased risk of bladder and other cancers associated with arsenic exposure, but the level at which it poses a measurable health risk has been the topic of considerable debate, and its precise mechanism of action remains unknown. Furthermore, a number of studies have reported an interaction between smoking, genetic polymorphisms and cancer risk. We will test the hypothesis that polymorphisms in the nucleotide excision repair pathway are associated with increased bladder cancer risk. We will address this hypothesis using exposure data and blood samples collected in a large population-based study of bladder cancer in the New Hampshire (850 cases, 1,365 controls). The specific aims of the project will be to 1) test the hypothesis that genetic variants in the nucleotide excision repair pathway genes (XPD, XPC, XPA, and ERCC1), are associated with increased risk of bladder cancer, and 2) determine whether environmental exposures (arsenic, smoking) and nucleotide excision repair polymorphisms interact to increase bladder cancer risk. This study presents a unique opportunity to clarify how genetic and environmental factors affect DNA repair and contribute to bladder cancer susceptibility. Through our study, we hope to contribute to both our mechanistic understanding of bladder cancer and to identify subgroups of the population that may be at greater risk of environmentally-induced cancers.

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Publications

Expression of tumor suppressive microRNA-34a is associated with a reduced risk of bladder cancer recurrence.
Authors: Andrew A.S. , Marsit C.J. , Schned A.R. , Seigne J.D. , Kelsey K.T. , Moore J.H. , Perreard L. , Karagas M.R. , Sempere L.F. .
Source: International journal of cancer, 2015-09-01; 137(5), p. 1158-66.
EPub date: 2015-02-25.
PMID: 25556547
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Genetic polymorphisms modify bladder cancer recurrence and survival in a USA population-based prognostic study.
Authors: Andrew A.S. , Gui J. , Hu T. , Wyszynski A. , Marsit C.J. , Kelsey K.T. , Schned A.R. , Tanyos S.A. , Pendleton E.M. , Ekstrom R.M. , et al. .
Source: BJU international, 2015 Feb; 115(2), p. 238-47.
EPub date: 2014-03-26.
PMID: 24666523
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Using Bayesian networks to discover relations between genes, environment, and disease.
Authors: Su C. , Andrew A. , Karagas M.R. , Borsuk M.E. .
Source: BioData mining, 2013-03-21; 6(1), p. 6.
EPub date: 2013-03-21.
PMID: 23514120
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HSD3B and gene-gene interactions in a pathway-based analysis of genetic susceptibility to bladder cancer.
Authors: Andrew A.S. , Hu T. , Gu J. , Gui J. , Ye Y. , Marsit C.J. , Kelsey K.T. , Schned A.R. , Tanyos S.A. , Pendleton E.M. , et al. .
Source: PloS one, 2012; 7(12), p. e51301.
EPub date: 2012-12-19.
PMID: 23284679
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Arsenic exposure predicts bladder cancer survival in a US population.
Authors: Kwong R.C. , Karagas M.R. , Kelsey K.T. , Mason R.A. , Tanyos S.A. , Schned A.R. , Marsit C.J. , Andrew A.S. .
Source: World journal of urology, 2010 Aug; 28(4), p. 487-92.
EPub date: 2009-10-16.
PMID: 19834714
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EGFR pathway polymorphisms and bladder cancer susceptibility and prognosis.
Authors: Mason R.A. , Morlock E.V. , Karagas M.R. , Kelsey K.T. , Marsit C.J. , Schned A.R. , Andrew A.S. .
Source: Carcinogenesis, 2009 Jul; 30(7), p. 1155-60.
EPub date: 2009-04-16.
PMID: 19372140
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Bladder cancer SNP panel predicts susceptibility and survival.
Authors: Andrew A.S. , Gui J. , Sanderson A.C. , Mason R.A. , Morlock E.V. , Schned A.R. , Kelsey K.T. , Marsit C.J. , Moore J.H. , Karagas M.R. .
Source: Human genetics, 2009 Jun; 125(5-6), p. 527-39.
EPub date: 2009-03-01.
PMID: 19252927
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Arsenic activates EGFR pathway signaling in the lung.
Authors: Andrew A.S. , Mason R.A. , Memoli V. , Duell E.J. .
Source: Toxicological sciences : an official journal of the Society of Toxicology, 2009 Jun; 109(2), p. 350-7.
EPub date: 2009-01-23.
PMID: 19168569
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DNA repair genotype interacts with arsenic exposure to increase bladder cancer risk.
Authors: Andrew A.S. , Mason R.A. , Kelsey K.T. , Schned A.R. , Marsit C.J. , Nelson H.H. , Karagas M.R. .
Source: Toxicology letters, 2009-05-22; 187(1), p. 10-4.
EPub date: 2009-01-20.
PMID: 19429237
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A computationally efficient hypothesis testing method for epistasis analysis using multifactor dimensionality reduction.
Authors: Pattin K.A. , White B.C. , Barney N. , Gui J. , Nelson H.H. , Kelsey K.T. , Andrew A.S. , Karagas M.R. , Moore J.H. .
Source: Genetic epidemiology, 2009 Jan; 33(1), p. 87-94.
PMID: 18671250
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Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population.
Authors: Andrew A.S. , Jewell D.A. , Mason R.A. , Whitfield M.L. , Moore J.H. , Karagas M.R. .
Source: Environmental health perspectives, 2008 Apr; 116(4), p. 524-31.
PMID: 18414638
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DNA repair polymorphisms modify bladder cancer risk: a multi-factor analytic strategy.
Authors: Andrew A.S. , Karagas M.R. , Nelson H.H. , Guarrera S. , Polidoro S. , Gamberini S. , Sacerdote C. , Moore J.H. , Kelsey K.T. , Demidenko E. , et al. .
Source: Human heredity, 2008; 65(2), p. 105-18.
EPub date: 2007-09-26.
PMID: 17898541
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Exposure to arsenic at levels found inU.S. drinking water modifies expression in the mouse lung.
Authors: Andrew A.S. , Bernardo V. , Warnke L.A. , Davey J.C. , Hampton T. , Mason R.A. , Thorpe J.E. , Ihnat M.A. , Hamilton J.W. .
Source: Toxicological sciences : an official journal of the Society of Toxicology, 2007 Nov; 100(1), p. 75-87.
EPub date: 2007-08-06.
PMID: 17682005
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Arsenic exposure is associated with decreased DNA repair in vitro and in individuals exposed to drinking water arsenic.
Authors: Andrew A.S. , Burgess J.L. , Meza M.M. , Demidenko E. , Waugh M.G. , Hamilton J.W. , Karagas M.R. .
Source: Environmental health perspectives, 2006 Aug; 114(8), p. 1193-8.
PMID: 16882524
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Concordance of multiple analytical approaches demonstrates a complex relationship between DNA repair gene SNPs, smoking and bladder cancer susceptibility.
Authors: Andrew A.S. , Nelson H.H. , Kelsey K.T. , Moore J.H. , Meng A.C. , Casella D.P. , Tosteson T.D. , Schned A.R. , Karagas M.R. .
Source: Carcinogenesis, 2006 May; 27(5), p. 1030-7.
EPub date: 2005-11-25.
PMID: 16311243
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