Grant Number:	2R01CA082354-09A2 Interpret this number
Primary Investigator:	Nelson, Heather
Organization:	University Of Minnesota
Project Title:	Molecular Epidemiology of Non-Melanoma Skin Cancer
Fiscal Year:	2009

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




A functional variant in the immune signalling receptor NKG2D alters skin cancer risk.
Authors: Vineretsky K.A. , Domingo-Musibay E. , Karagas M.R. , Lazovich D. , Kuriger-Laber J.K. , Hunter-Schlichting D. , Nelson H.H. .
Source: The British Journal Of Dermatology, 2021-12-08 00:00:00.0; , .
EPub date: 2021-12-08 00:00:00.0.
PMID: 34878657
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Skin Cancer Risk Is Modified By Kir/hla Interactions That Influence The Activation Of Natural Killer Immune Cells
Authors: Vineretsky K.A. , Karagas M.R. , Christensen B.C. , Kuriger-Laber J.K. , Perry A.E. , Storm C.A. , Nelson H.H. .
Source: Cancer Research, 2016-01-15 00:00:00.0; 76(2), p. 370-6.
PMID: 26744525
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Seroepidemiology Of Human Polyomaviruses In A Us Population
Authors: Gossai A. , Waterboer T. , Nelson H.H. , Michel A. , Willhauck-Fleckenstein M. , Farzan S.F. , Hoen A.G. , Christensen B.C. , Kelsey K.T. , Marsit C.J. , et al. .
Source: American Journal Of Epidemiology, 2016-01-01 00:00:00.0; 183(1), p. 61-9.
PMID: 26667254
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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.
EPub date: 2015-09-01 00:00:00.0.
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.
PMID: 24666523
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Leukocyte-adjusted Epigenome-wide Association Studies Of Blood From Solid Tumor Patients
Authors: Langevin S.M. , Houseman E.A. , Accomando W.P. , Koestler D.C. , Christensen B.C. , Nelson H.H. , Karagas M.R. , Marsit C.J. , Wiencke J.K. , Kelsey K.T. .
Source: Epigenetics, 2014 Jun; 9(6), p. 884-95.
PMID: 24671036
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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.
EPub date: 2014-02-01 00:00:00.0.
PMID: 24122218
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RNASEL and MIR146A SNP-SNP interaction as a susceptibility factor for non-melanoma skin cancer.
Authors: Farzan S.F. , Karagas M.R. , Christensen B.C. , Li Z. , Kuriger J.K. , Nelson H.H. , New Hampshire Skin Cancer Study .
Source: Plos One, 2014; 9(4), p. e93602.
PMID: 24699816
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Hla-c -35kb Expression Snp Is Associated With Differential Control Of ¿-hpv Infection In Squamous Cell Carcinoma Cases And Controls
Authors: Vineretsky K.A. , Karagas M.R. , Kuriger-Laber J.K. , Waterboer T. , Pawlita M. , Nelson H.H. .
Source: Plos One, 2014; 9(8), p. e103710.
PMID: 25083782
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Aberrant Promoter Methylation Of Cdh13 And Mgmt Genes Is Associated With Clinicopathologic Characteristics Of Primary Non-small-cell Lung Carcinoma
Authors: Kontic M. , Stojsic J. , Jovanovic D. , Bunjevacki V. , Ognjanovic S. , Kuriger J. , Puumala S. , Nelson H.H. .
Source: Clinical Lung Cancer, 2012 Jul; 13(4), p. 297-303.
PMID: 22169480
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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.
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The Influence Of Aging, Environmental Exposures And Local Sequence Features On The Variation Of Dna Methylation In Blood
Authors: Langevin S.M. , Houseman E.A. , Christensen B.C. , Wiencke J.K. , Nelson H.H. , Karagas M.R. , Marsit C.J. , Kelsey K.T. .
Source: Epigenetics, 2011 Jul; 6(7), p. 908-19.
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The Role Of Tp53 And Mdm2 Polymorphisms In Tp53 Mutagenesis And Risk Of Non-melanoma Skin Cancer
Authors: Almquist L.M. , Karagas M.R. , Christensen B.C. , Welsh M.M. , Perry A.E. , Storm C.A. , Nelson H.H. .
Source: Carcinogenesis, 2011 Mar; 32(3), p. 327-30.
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Genetic Determinants Of Uv-susceptibility In Non-melanoma Skin Cancer
Authors: Welsh M.M. , Karagas M.R. , Kuriger J.K. , Houseman A. , Spencer S.K. , Perry A.E. , Nelson H.H. .
Source: Plos One, 2011; 6(7), p. e20019.
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Breast cancer DNA methylation profiles are associated with tumor size and alcohol and folate intake.
Authors: Christensen B.C. , Kelsey K.T. , Zheng S. , Houseman E.A. , Marsit C.J. , Wrensch M.R. , Wiemels J.L. , Nelson H.H. , Karagas M.R. , Kushi L.H. , et al. .
Source: Plos Genetics, 2010-07-29 00:00:00.0; 6(7), p. e1001043.
EPub date: 2010-07-29 00:00:00.0.
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Oral Contraceptives: A Risk Factor For Squamous Cell Carcinoma?
Authors: Applebaum K.M. , Nelson H.H. , Zens M.S. , Stukel T.A. , Spencer S.K. , Karagas M.R. .
Source: The Journal Of Investigative Dermatology, 2009 Dec; 129(12), p. 2760-5.
PMID: 19554020
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New Common Variants Affecting Susceptibility To Basal Cell Carcinoma
Authors: Stacey S.N. , Sulem P. , Masson G. , Gudjonsson S.A. , Thorleifsson G. , Jakobsdottir M. , Sigurdsson A. , Gudbjartsson D.F. , Sigurgeirsson B. , Benediktsdottir K.R. , et al. .
Source: Nature Genetics, 2009 Aug; 41(8), p. 909-14.
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Ctla4 Variants, Uv-induced Tolerance, And Risk Of Non-melanoma Skin Cancer
Authors: Welsh M.M. , Applebaum K.M. , Spencer S.K. , Perry A.E. , Karagas M.R. , Nelson H.H. .
Source: Cancer Research, 2009-08-01 00:00:00.0; 69(15), p. 6158-63.
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Bladder cancer SNP panel predicts susceptibility and survival.
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Source: Human Genetics, 2009 Jun; 125(5-6), p. 527-39.
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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.
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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.
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Exposure profiles and human papillomavirus infection in skin cancer: an analysis of 25 genus beta-types in a population-based study.
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Source: The Journal Of Investigative Dermatology, 2008 Dec; 128(12), p. 2888-93.
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A Role For Ultraviolet Radiation Immunosuppression In Non-melanoma Skin Cancer As Evidenced By Gene-environment Interactions
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Cutaneous Human Papillomavirus Infection, The Ever2 Gene And Incidence Of Squamous Cell Carcinoma: A Case-control Study
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Source: International Journal Of Cancer, 2008-05-15 00:00:00.0; 122(10), p. 2377-9.
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DNA repair polymorphisms modify bladder cancer risk: a multi-factor analytic strategy.
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Reported use of photosensitizing medications and basal cell and squamous cell carcinoma of the skin: results of a population-based case-control study.
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Squamous cell and basal cell carcinoma of the skin in relation to radiation therapy and potential modification of risk by sun exposure.
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Gene-drug Interaction At The Glucocorticoid Receptor Increases Risk Of Squamous Cell Skin Cancer
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Polymorphisms In Nucleotide Excision Repair Genes, Arsenic Exposure, And Non-melanoma Skin Cancer In New Hampshire
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Measures Of Cumulative Exposure From A Standardized Sun Exposure History Questionnaire: A Comparison With Histologic Assessment Of Solar Skin Damage
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Xpa, Haplotypes, And Risk Of Basal And Squamous Cell Carcinoma
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Arsenic exposure is associated with decreased DNA repair in vitro and in individuals exposed to drinking water arsenic.
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Concordance of multiple analytical approaches demonstrates a complex relationship between DNA repair gene SNPs, smoking and bladder cancer susceptibility.
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Allelic Loss At Drosophila Patched Gene Is Highly Prevalent In Basal And Squamous Cell Carcinomas Of The Skin
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The XPC poly-AT polymorphism in non-melanoma skin cancer.
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Gender, smoking, glutathione-S-transferase variants and bladder cancer incidence: a population-based study.
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A population-based case-control study of the XRCC1 Arg399Gln polymorphism and susceptibility to bladder cancer.
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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.
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The molecular epidemiology of asbestos and tobacco in lung cancer.
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Microsatellite instability at tetranucleotide repeats in skin and bladder cancer.
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The XRCC1 Arg399Gln polymorphism, sunburn, and non-melanoma skin cancer: evidence of gene-environment interaction.
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Fas/APO-1 promoter polymorphism is not associated with non-melanoma skin cancer.
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