The development of head and neck cancer may depend upon an interaction between both environmental carcinogens and a genetic susceptibility to those carcinogens. The need to understand such interaction in the head and neck cancer population is heightened by their associated risk for the development of second primary neoplasias, such as lung and digestive tract cancers. With an improved understanding, the relative risk of second malignancies can be more precisely defined. Preventive therapy could then be more appropriately targeted. The head and neck cancer population thus represents a potential target population for prevention of multiple diverse environmentally-induced cancers. This proposal is comprised of a series of objectives in which the primary goal is to establish a quantitative risk assessment model for second primary malignancies in head and neck cancer patients. We will demonstrate that the addition of quantitative measures of mutagen-sensitivity expressed by a respective patient will significantly improve that model. The relationship of total carcinogen exposure (namely to tobacco and alcohol) both before and after treatment to the development of second primary malignancies will be established. Mutagen-sensitivity will be determined by culturing lymphocytes from each patient, arresting lymphocytes in metaphase, exposing them to the clastogen bleomycin, and assessing for bleomycin-induced chromatid breaks in cytogenetic preparations. Results from this study will form a basis for determining the potential biologic significance of chromosomal sensitivity in cancer development. Results will, likewise, provide insight into future stratification considerations for therapeutic intervention trials involving prevention of second malignancies in the head and beck cancer population.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
3P01CA052051-05S1
Application #
5207634
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1996
Total Cost
Indirect Cost
Hildebrandt, Michelle A T; Lippman, Scott M; Etzel, Carol J et al. (2012) Genetic variants in the PI3K/PTEN/AKT/mTOR pathway predict head and neck cancer patient second primary tumor/recurrence risk and response to retinoid chemoprevention. Clin Cancer Res 18:3705-13
Lee, J Jack; Wu, Xifeng; Hildebrandt, Michelle A T et al. (2011) Global assessment of genetic variation influencing response to retinoid chemoprevention in head and neck cancer patients. Cancer Prev Res (Phila) 4:185-93
Wang, Jianming; Lippman, Scott M; Lee, J Jack et al. (2010) Genetic variations in regulator of G-protein signaling genes as susceptibility loci for second primary tumor/recurrence in head and neck squamous cell carcinoma. Carcinogenesis 31:1755-61
Zhang, Xiaofan; Yang, Hushan; Lee, J Jack et al. (2010) MicroRNA-related genetic variations as predictors for risk of second primary tumor and/or recurrence in patients with early-stage head and neck cancer. Carcinogenesis 31:2118-23
Wu, Xifeng; Spitz, Margaret R; Lee, J Jack et al. (2009) Novel susceptibility loci for second primary tumors/recurrence in head and neck cancer patients: large-scale evaluation of genetic variants. Cancer Prev Res (Phila) 2:617-24
William Jr, William N; Lee, J Jack; Lippman, Scott M et al. (2009) High-dose fenretinide in oral leukoplakia. Cancer Prev Res (Phila) 2:22-6
Papadimitrakopoulou, Vassiliki A; Lee, J Jack; William Jr, William N et al. (2009) Randomized trial of 13-cis retinoic acid compared with retinyl palmitate with or without beta-carotene in oral premalignancy. J Clin Oncol 27:599-604
Kawaguchi, Hidetoshi; El-Naggar, Adel K; Papadimitrakopoulou, Vali et al. (2008) Podoplanin: a novel marker for oral cancer risk in patients with oral premalignancy. J Clin Oncol 26:354-60
Lippman, Scott M; Lee, J Jack; Martin, Jack W et al. (2006) Fenretinide activity in retinoid-resistant oral leukoplakia. Clin Cancer Res 12:3109-14
Khuri, Fadlo R; Lee, J Jack; Lippman, Scott M et al. (2006) Randomized phase III trial of low-dose isotretinoin for prevention of second primary tumors in stage I and II head and neck cancer patients. J Natl Cancer Inst 98:441-50

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