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National Institutes of Health: National Cancer Institute: Division of Cancer Control and Population Sciences
Grant Details

Grant Number: 5R01CA082354-11 Interpret this number
Primary Investigator: Nelson, Heather
Organization: University Of Minnesota
Project Title: Molecular Epidemiology of Non-Melanoma Skin Cancer
Fiscal Year: 2011
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Abstract

DESCRIPTION (provided by applicant): Non-melanoma skin cancers (NMSC) are the most prevalent malignancies among Caucasians. Further, skin cancer is a model system for understanding carcinogenesis and genetic susceptibility to environmentally-induced cancers. Our prior work on genetic susceptibility has focused on mutagenicity pathways, testing hypotheses regarding polymorphisms in DNA repair genes and genes in oxidative stress detoxification. Moving forward, we will continue to build on the tremendous existing resource of a large population-based case control study in New Hampshire (approximately 1500 basal cell carcinoma (BCC), 1200 squamous cell carcinoma (SCC) and 1400 controls, principal investigator: Karagas, CA57494). In this new grant period we will shift our focus to alternative pathways of susceptibility in NMSC, focusing on the role of immune signaling. Ultraviolet radiation (UV) is well documented to induce local and systemic immunosuppression. We will address genetic susceptibility to NMSC targeting immune signaling and inflammation pathways. These findings will be directly translatable to other cancers and disease processes. This application aims to identify genetic variation in immune signaling pathways that enhances susceptibility to skin cancer. Identified genes would be useful in understanding skin cancer prevention, as well as other diseases with a strong immune component (i.e. autoimmune disease and vaccine efficiency). PUBLIC HEALTH RELEVANCE: Ultraviolet radiation (UV) is well documented to induce local and systemic immunosuppression. This application aims to identify genetic variation in immune signaling pathways that enhances susceptibility to skin cancer. Identified genes would be useful in understanding skin cancer prevention, as well as other diseases with a strong immune component

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Publications

Fas/apo-1 Promoter Polymorphism Is Not Associated With Non-melanoma Skin Cancer
Authors: Nelson H.H. , Kelsey K.T. , Bronson M.H. , Mott L.A. , Karagas M.R. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2001 Jul; 10(7), p. 809-10.
PMID: 11440968
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The Xrcc1 Arg399gln Polymorphism, Sunburn, And Non-melanoma Skin Cancer: Evidence Of Gene-environment Interaction
Authors: Nelson H.H. , Kelsey K.T. , Mott L.A. , Karagas M.R. .
Source: Cancer Research, 2002-01-01 00:00:00.0; 62(1), p. 152-5.
PMID: 11782372
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Microsatellite Instability At Tetranucleotide Repeats In Skin And Bladder Cancer
Authors: Danaee H. , Nelson H.H. , Karagas M.R. , Schned A.R. , Ashok T.D. , Hirao T. , Perry A.E. , Kelsey K.T. .
Source: Oncogene, 2002-07-25 00:00:00.0; 21(32), p. 4894-9.
PMID: 12118368
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The Molecular Epidemiology Of Asbestos And Tobacco In Lung Cancer
Authors: Nelson H.H. , Kelsey K.T. .
Source: Oncogene, 2002-10-21 00:00:00.0; 21(48), p. 7284-8.
PMID: 12379872
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Low Dose Exposure To Sodium Arsenite Synergistically Interacts With Uv Radiation To Induce Mutations And Alter Dna Repair In Human Cells
Authors: Danaee H. , Nelson H.H. , Liber H. , Little J.B. , Kelsey K.T. .
Source: Mutagenesis, 2004 Mar; 19(2), p. 143-8.
PMID: 14981161
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A Population-based Case-control Study Of The Xrcc1 Arg399gln Polymorphism And Susceptibility To Bladder Cancer
Authors: Kelsey K.T. , Park S. , Nelson H.H. , Karagas M.R. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2004 Aug; 13(8), p. 1337-41.
PMID: 15298955
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Gender, Smoking, Glutathione-s-transferase Variants And Bladder Cancer Incidence: A Population-based Study
Authors: Karagas M.R. , Park S. , Warren A. , Hamilton J. , Nelson H.H. , Mott L.A. , Kelsey K.T. .
Source: Cancer Letters, 2005-02-28 00:00:00.0; 219(1), p. 63-9.
PMID: 15694665
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The Xpc Poly-at Polymorphism In Non-melanoma Skin Cancer
Authors: Nelson H.H. , Christensen B. , Karagas M.R. .
Source: Cancer Letters, 2005-05-26 00:00:00.0; 222(2), p. 205-9.
PMID: 15863269
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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.
PMID: 16311243
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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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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.
PMID: 17898541
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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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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.
PMID: 19252927
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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 00:00:00.0; 187(1), p. 10-4.
PMID: 19429237
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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.
PMID: 23284679
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Body Mass And Smoking Are Modifiable Risk Factors For Recurrent Bladder Cancer
Authors: Wyszynski A. , Tanyos S.A. , Rees J.R. , Marsit C.J. , Kelsey K.T. , Schned A.R. , Pendleton E.M. , Celaya M.O. , Zens M.S. , Karagas M.R. , et al. .
Source: Cancer, 2014-02-01 00:00:00.0; 120(3), p. 408-14.
PMID: 24122218
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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.
PMID: 24666523
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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 00:00:00.0; 137(5), p. 1158-66.
PMID: 25556547
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