Although tobacco smoke and alcohol account for most cases of oral cancer, few smokers and drinkers eventually acquire this disease. The main goal of this study is to determine whether differences in constitutive function of certain biotransformation enzymes (which metabolize tobacco smoke and alcohol) modify risk for oral cancer among smokers and drinkers, and thereby account for some of the observed differences in susceptibility. To meet this goal, we will conduct a case-control study of oral cancer in the Pittsburgh area. Cases (N=244) will be men and women identified through the Ear, Nose, and Throat, and Oncology Offices at UPMC with squamous cell carcinoma of the oral cavity newly diagnosed between 01/01/99 and 12/31/02, who are 18-74 years of age, and reside in one of 16 counties in the Tri-State area (including western Pennsylvania, eastern Ohio and northeastern Western Virginia). Neighborhood controls (N=488) will be men and women identified through Voters' Registration lists (for Allegheny County in Pennsylvania) or Motor Vehicle Drivers' License lists (for all other counties) who are without oral cancer and match the cases on age, gender, race and zip code. Two controls will be matched to each case. Eligible cases and controls will have a history of cigarette use (at least 10 pack-years) or alcohol use (at least 1 alcoholic beverage per week). In person interviews will cover demographic variables, detailed history of tobacco and alcohol use, diet, ethnic background and family history of cancer. Blood will be drawn, and DNA extracted and analyzed for genetic variants of the following polymorphic biotransformation enzymes: CYP1A1, CYP2E1, GSTM1, GSTT1, GSTP1, mEH, MPO, NAT2, ALDH2, ADH2 and ADH3. Each of these enzymes is important in the metabolism of either alcohol or tobacco smoke, or both. We will measure relationships between each genetic enzyme variant and risk for oral cancer, as well as the joint effects of these polymorphisms on risk. We will also examine exposures, e.g. diet, that may modify or confound these relationships. Identification of genetic biomarkers for susceptibility to oral cancer could be used to focus screening and intervention efforts on individuals who at highest risk for this disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Comprehensive Center (P60)
Project #
5P60DE013059-03
Application #
6480426
Study Section
Project Start
1999-08-01
Project End
2004-07-31
Budget Start
Budget End
Support Year
3
Fiscal Year
2001
Total Cost
$227,172
Indirect Cost
Name
University of Pittsburgh
Department
Type
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Sobo-Vujanovic, Andrea; Munich, Stephan; Vujanovic, Nikola L (2014) Dendritic-cell exosomes cross-present Toll-like receptor-ligands and activate bystander dendritic cells. Cell Immunol 289:119-27
Baskic, Dejan; Vujanovic, Lazar; Arsenijevic, Nebojsa et al. (2013) Suppression of natural killer-cell and dendritic-cell apoptotic tumoricidal activity in patients with head and neck cancer. Head Neck 35:388-98
Wan, Xiao Chloe; Egloff, Ann Marie; Johnson, Jonas (2012) Histological assessment of cervical lymph node identifies patients with head and neck squamous cell carcinoma (HNSCC): who would benefit from chemoradiation after surgery? Laryngoscope 122:2712-22
Zhong, Shilong; Nukui, Tomoko; Buch, Shama et al. (2011) Effects of ERCC2 Lys751Gln (A35931C) and CCND1 (G870A) polymorphism on outcome of advanced-stage squamous cell carcinoma of the head and neck are treatment dependent. Cancer Epidemiol Biomarkers Prev 20:2429-37
Ge, Lisheng; Baskic, Dejan; Basse, Per et al. (2009) Sheddase activity of tumor necrosis factor-alpha converting enzyme is increased and prognostically valuable in head and neck cancer. Cancer Epidemiol Biomarkers Prev 18:2913-22
Martin, Christa Lese; Reshmi, Shalini C; Ried, Thomas et al. (2008) Chromosomal imbalances in oral squamous cell carcinoma: examination of 31 cell lines and review of the literature. Oral Oncol 44:369-82
Buch, Shama C; Nazar-Stewart, Valle; Weissfeld, Joel L et al. (2008) Case-control study of oral and oropharyngeal cancer in whites and genetic variation in eight metabolic enzymes. Head Neck 30:1139-47
White, Jason S; Weissfeld, Joel L; Ragin, Camille C R et al. (2007) The influence of clinical and demographic risk factors on the establishment of head and neck squamous cell carcinoma cell lines. Oral Oncol 43:701-12
Xu, Jun; Chakrabarti, Ayan K; Tan, Jennifer L et al. (2007) Essential role of the TNF-TNFR2 cognate interaction in mouse dendritic cell-natural killer cell crosstalk. Blood 109:3333-41
Makarenkova, Valeria; Chakrabarti, Ayan K; Liberatore, Jennifer A et al. (2005) Dendritic cells and natural killer cells interact via multiple TNF family molecules. J Leukoc Biol 77:408-13

Showing the most recent 10 out of 39 publications