Non-melanoma skin cancer is the most prevalent malignancy in the US, resulting in significant morbidity and health-care expense. Epidemiologic investigations have identified exposure to ultraviolet radiation as the primary risk factor for this disease; other environmental exposures that contribute to risk include ionizing radiation, arsenic, polycyclic aromatic hydrocarbons, and chronic immunosuppression. Host factors associated with increased risk for non-melanoma skin cancer include increasing age, male gender, and sun sensitive skin type. Basal cell and squamous cell carcinomas have been shown to contain alterations in the p53 gene, and recent work has identified a gene on chromosome 9q22, ptch, that is hypothesized to be critical in basal cell carcinoma tumorigenesis. These findings, while informative, are derived from relatively small, selected groups of patients and reflects the paucity of population-based molecular epidemiology for this disease. We propose to expand a large, well-established case-control study of non-melanoma skin cancer in New Hampshire to include investigation of genetic susceptibility. The project will focus on genes that potentially modify ultraviolet radiation exposure, including polymorphisms in the glutathione S-transferases (GSTM1, GSTT1, and GSTP1) and the newly identified variants in DNA excision repair genes (ERCC2/XPD, and XPF). In addition, we will collect tumor specimens from cases for characterization of mutations at p53 and 9q22/ptch. We will determine mutation spectra examine associations of mutation with carcinogenic exposures and patient traits, and refine a novel model of skin tumorigenesis. These studies will increase our understanding of host susceptibility to non-melanoma skin cancer and advance current models of skin carcinogenesis through identification of patterns of gene inactivation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA082354-02
Application #
6173618
Study Section
Special Emphasis Panel (ZRG1-EDC-2 (02))
Program Officer
Verma, Mukesh
Project Start
1999-09-30
Project End
2003-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
2
Fiscal Year
2000
Total Cost
$352,932
Indirect Cost
Name
Harvard University
Department
Genetics
Type
Schools of Public Health
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02115
Vineretsky, Karin A; Karagas, Margaret R; Christensen, Brock C et al. (2016) Skin Cancer Risk Is Modified by KIR/HLA Interactions That Influence the Activation of Natural Killer Immune Cells. Cancer Res 76:370-6
Gossai, Anala; Waterboer, Tim; Nelson, Heather H et al. (2016) Seroepidemiology of Human Polyomaviruses in a US Population. Am J Epidemiol 183:61-9
Andrew, Angeline S; Marsit, Carmen J; Schned, Alan R et al. (2015) Expression of tumor suppressive microRNA-34a is associated with a reduced risk of bladder cancer recurrence. Int J Cancer 137:1158-66
Andrew, Angeline S; Gui, Jiang; Hu, Ting et al. (2015) Genetic polymorphisms modify bladder cancer recurrence and survival in a USA population-based prognostic study. BJU Int 115:238-47
Langevin, Scott M; Houseman, E Andres; Accomando, William P et al. (2014) Leukocyte-adjusted epigenome-wide association studies of blood from solid tumor patients. Epigenetics 9:884-95
Wyszynski, Asaf; Tanyos, Sam A; Rees, Judy R et al. (2014) Body mass and smoking are modifiable risk factors for recurrent bladder cancer. Cancer 120:408-14
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
Farzan, Shohreh F; Karagas, Margaret R; Christensen, Brock C et al. (2014) RNASEL and MIR146A SNP-SNP interaction as a susceptibility factor for non-melanoma skin cancer. PLoS One 9:e93602
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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