Abstract

This study will use DNA, previously collected by the applicants from a well characterized population of lung cancer cases and controls, to study two classes of genes involved in the genesis of lung cancer, including oncogenes (K-ras) and tumor suppressor genes (P53 and genes on chromosome 3p). The application proposes to study mutations at these three loci, hypothesizing that specific alterations in these genes and loss of heterozygosity at chromosome 3p will describe aetiologic subclassifications associated with epidemiologically defined patterns of exposure to carcinogens of interest (e.g., smoking and asbestos) modified by the polymorphic metabolic traits and diet. Fundamental to this application is the hypothesis that lung cancers arise through different pathways and that these pathways reflect the patterns of exposure and susceptibility of individuals to the action of aetiologically important patterns of exposure and susceptibility of individuals to the action of aetiologically important carcinogens. The relationship of alterations in these genes to DNA adduct burden in normal lung tissue will be examined, along with mononuclear cell DNA.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
1R01ES008357-01
Application #
2018793
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1997-01-01
Project End
2000-12-31
Budget Start
1997-01-01
Budget End
1997-12-31
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Harvard University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Hasegawa, Masayuki; Nelson, Heather H; Peters, Edward et al. (2002) Patterns of gene promoter methylation in squamous cell cancer of the head and neck. Oncogene 21:4231-6
Wiencke, John K; Kelsey, Karl T (2002) Teen smoking, field cancerization, and a ""critical period"" hypothesis for lung cancer susceptibility. Environ Health Perspect 110:555-8
Schaeffner, E S; Miller, D P; Wain, J C et al. (2001) Use of an asbestos exposure score and the presence of pleural and parenchymal abnormalities in a lung cancer case series. Int J Occup Environ Health 7:14-8
Kim, D H; Nelson, H H; Wiencke, J K et al. (2001) p16(INK4a) and histology-specific methylation of CpG islands by exposure to tobacco smoke in non-small cell lung cancer. Cancer Res 61:3419-24
Hirao, T; Nelson, H H; Ashok, T D et al. (2001) Tobacco smoke-induced DNA damage and an early age of smoking initiation induce chromosome loss at 3p21 in lung cancer. Cancer Res 61:612-5
Fan, R; Wu, M T; Miller, D et al. (2000) The p53 codon 72 polymorphism and lung cancer risk. Cancer Epidemiol Biomarkers Prev 9:1037-42
Nelson, H H; Christiani, D C; Mark, E J et al. (1999) Implications and prognostic value of K-ras mutation for early-stage lung cancer in women. J Natl Cancer Inst 91:2032-8
Wiencke, J K; Thurston, S W; Kelsey, K T et al. (1999) Early age at smoking initiation and tobacco carcinogen DNA damage in the lung. J Natl Cancer Inst 91:614-9
Nelson, H H; Christiani, D C; Wiencke, J K et al. (1999) k-ras mutation and occupational asbestos exposure in lung adenocarcinoma: asbestos-related cancer without asbestosis. Cancer Res 59:4570-3
Wang, X; Christiani, D C; Mark, E J et al. (1999) Carcinogen exposure, p53 alteration, and K-ras mutation in synchronous multiple primary lung carcinoma. Cancer 85:1734-9

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