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

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA082354-10
Application #
7851050
Study Section
Special Emphasis Panel (ZRG1-HOP-T (08))
Program Officer
Mechanic, Leah E
Project Start
1999-09-30
Project End
2012-04-30
Budget Start
2010-05-06
Budget End
2011-04-30
Support Year
10
Fiscal Year
2010
Total Cost
$418,087
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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Vineretsky, Karin A; Karagas, Margaret R; Kuriger-Laber, Jacquelyn K et al. (2014) HLA-C -35kb expression SNP is associated with differential control of ?-HPV infection in squamous cell carcinoma cases and controls. PLoS One 9:e103710
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Andrew, Angeline S; Hu, Ting; Gu, Jian et al. (2012) HSD3B and gene-gene interactions in a pathway-based analysis of genetic susceptibility to bladder cancer. PLoS One 7:e51301
Kontic, Milica; Stojsic, Jelena; Jovanovic, Dragana et al. (2012) Aberrant Promoter Methylation of CDH13 and MGMT Genes is Associated With Clinicopathologic Characteristics of Primary Non-Small-Cell Lung Carcinoma. Clin Lung Cancer 13:297-303

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