There is a need for early molecular indicators of the efficacy of chemoprevention and of interindividual variation in potential risk reduciton. A double-blind, placebo-controlled intervention trial is proposed using biologic markers to evaluate whether supplementation with antioxidant micronutrients reduces DNA damage in a cohort of 300 cigarette smokers and whether genetic factors modulate the effects of the micronutrients. Study subjects will be recruited through the New York State Psychiatric Institute and will be randomized into placebo or vitamin treatment groups. The latter will receive 400 IU vitamin E, and 500 mg vitamin C, based on experimental and epidemiologic evidence that these micronutrients inhibit DNA damage and tumor formation. Biomarkers of DNA damage and plasma vitamin levels will be evaluated in blood sample drawn at baseline and at three month intervals over one year of treatment and one year of follow-up. Buccal cells will be stored for future analyses. The study will address three specific issues: 1) whether suppplementation reduces smoking-induced DNA damage (aromatic-DNA adducts and oxidative DNA damage, including 8-hydorxydeoxyguanine and 5-hydroxymethyl-2'deoxyuridine in peripheral mononuclear cells); 2) whether DNA damage increases significantly after cessation fo vitamin supplementation; and 3) whether genetic susceptibility factors (glutathione-S-transferase M1 deletion and CYHP1A1 polymorphisms) modulate the relationship between DNA damage and antioxidant micronutrients. This type of validation study is a prerequisite to incorporating markers of DNA damage and plasma micronutrients into large-scale, long-term intervention studies designed to look at reduction of cancer incidence in smokers and ex-smokers. Once validated in this model population, these biomarkers would also have applicability in evaluating interventions in occupational cohorts and other populations highly exposed to carcinogens.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
3R01CA069094-04S4
Application #
6500638
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Rosenfeld, Bobby
Project Start
1996-09-24
Project End
2002-06-30
Budget Start
1999-07-01
Budget End
2002-06-30
Support Year
4
Fiscal Year
2001
Total Cost
$75,210
Indirect Cost
Name
Columbia University (N.Y.)
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Perera, Frederica P; Vineis, Paolo (2011) Cancer. IARC Sci Publ :337-62
Vineis, Paolo; Perera, Frederica (2007) Molecular epidemiology and biomarkers in etiologic cancer research: the new in light of the old. Cancer Epidemiol Biomarkers Prev 16:1954-65
Mooney, Laverne A; Madsen, Ann M; Tang, Deliang et al. (2005) Antioxidant vitamin supplementation reduces benzo(a)pyrene-DNA adducts and potential cancer risk in female smokers. Cancer Epidemiol Biomarkers Prev 14:237-42
Mooney, L A; Perera, F P; Van Bennekum, A M et al. (2001) Gender differences in autoantibodies to oxidative DNA base damage in cigarette smokers. Cancer Epidemiol Biomarkers Prev 10:641-8
Huang, X; Powell, J; Mooney, L A et al. (2001) Importance of complete DNA digestion in minimizing variability of 8-oxo-dG analyses. Free Radic Biol Med 31:1341-51
Perera, F P (2000) Molecular epidemiology: on the path to prevention? J Natl Cancer Inst 92:602-12
Perera, F P; Weinstein, I B (2000) Molecular epidemiology: recent advances and future directions. Carcinogenesis 21:517-24