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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

Body mass and smoking are modifiable risk factors for recurrent bladder cancer.
Authors: Wyszynski A, Tanyos SA, Rees JR, Marsit CJ, Kelsey KT, Schned AR, Pendleton EM, Celaya MO, Zens MS, Karagas MR, Andrew AS
Source: Cancer, 2014 Feb 1;120(3), p. 408-14.
EPub date: 2013 Oct 10.
PMID: 24122218
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HSD3B and gene-gene interactions in a pathway-based analysis of genetic susceptibility to bladder cancer.
Authors: Andrew AS, Hu T, Gu J, Gui J, Ye Y, Marsit CJ, Kelsey KT, Schned AR, Tanyos SA, Pendleton EM, Mason RA, Morlock EV, Zens MS, Li Z, Moore JH, Wu X, Karagas MR
Source: PLoS One, 2012;7(12), p. e51301.
EPub date: 2012 Dec 19.
PMID: 23284679
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DNA repair genotype interacts with arsenic exposure to increase bladder cancer risk.
Authors: Andrew AS, Mason RA, Kelsey KT, Schned AR, Marsit CJ, Nelson HH, Karagas MR
Source: Toxicol Lett, 2009 May 22;187(1), p. 10-4.
EPub date: 2009 Jan 20.
PMID: 19429237
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Bladder cancer SNP panel predicts susceptibility and survival.
Authors: Andrew AS, Gui J, Sanderson AC, Mason RA, Morlock EV, Schned AR, Kelsey KT, Marsit CJ, Moore JH, Karagas MR
Source: Hum Genet, 2009 Jun;125(5-6), p. 527-39.
EPub date: 2009 Mar 1.
PMID: 19252927
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A computationally efficient hypothesis testing method for epistasis analysis using multifactor dimensionality reduction.
Authors: Pattin KA, White BC, Barney N, Gui J, Nelson HH, Kelsey KT, Andrew AS, Karagas MR, Moore JH
Source: Genet Epidemiol, 2009 Jan;33(1), p. 87-94.
PMID: 18671250
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DNA repair polymorphisms modify bladder cancer risk: a multi-factor analytic strategy.
Authors: Andrew AS, Karagas MR, Nelson HH, Guarrera S, Polidoro S, Gamberini S, Sacerdote C, Moore JH, Kelsey KT, Demidenko E, Vineis P, Matullo G
Source: Hum Hered, 2008;65(2), p. 105-18.
EPub date: 2007 Sep 26.
PMID: 17898541
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Arsenic exposure is associated with decreased DNA repair in vitro and in individuals exposed to drinking water arsenic.
Authors: Andrew AS, Burgess JL, Meza MM, Demidenko E, Waugh MG, Hamilton JW, Karagas MR
Source: Environ Health Perspect, 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 AS, Nelson HH, Kelsey KT, Moore JH, Meng AC, Casella DP, Tosteson TD, Schned AR, Karagas MR
Source: Carcinogenesis, 2006 May;27(5), p. 1030-7.
EPub date: 2005 Nov 25.
PMID: 16311243
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The XPC poly-AT polymorphism in non-melanoma skin cancer.
Authors: Nelson HH, Christensen B, Karagas MR
Source: Cancer Lett, 2005 May 26;222(2), p. 205-9.
EPub date: 2005 Jan 7.
PMID: 15863269
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Gender, smoking, glutathione-S-transferase variants and bladder cancer incidence: a population-based study.
Authors: Karagas MR, Park S, Warren A, Hamilton J, Nelson HH, Mott LA, Kelsey KT
Source: Cancer Lett, 2005 Feb 28;219(1), p. 63-9.
PMID: 15694665
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A population-based case-control study of the XRCC1 Arg399Gln polymorphism and susceptibility to bladder cancer.
Authors: Kelsey KT, Park S, Nelson HH, Karagas MR
Source: Cancer Epidemiol Biomarkers Prev, 2004 Aug;13(8), p. 1337-41.
PMID: 15298955
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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 HH, Liber H, Little JB, Kelsey KT
Source: Mutagenesis, 2004 Mar;19(2), p. 143-8.
PMID: 14981161
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The molecular epidemiology of asbestos and tobacco in lung cancer.
Authors: Nelson HH, Kelsey KT
Source: Oncogene, 2002 Oct 21;21(48), p. 7284-8.
PMID: 12379872
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Microsatellite instability at tetranucleotide repeats in skin and bladder cancer.
Authors: Danaee H, Nelson HH, Karagas MR, Schned AR, Ashok TD, Hirao T, Perry AE, Kelsey KT
Source: Oncogene, 2002 Jul 25;21(32), p. 4894-9.
PMID: 12118368
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The XRCC1 Arg399Gln polymorphism, sunburn, and non-melanoma skin cancer: evidence of gene-environment interaction.
Authors: Nelson HH, Kelsey KT, Mott LA, Karagas MR
Source: Cancer Res, 2002 Jan 1;62(1), p. 152-5.
PMID: 11782372
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Fas/APO-1 promoter polymorphism is not associated with non-melanoma skin cancer.
Authors: Nelson HH, Kelsey KT, Bronson MH, Mott LA, Karagas MR
Source: Cancer Epidemiol Biomarkers Prev, 2001 Jul;10(7), p. 809-10.
PMID: 11440968
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