CHEMOPREVENTION IN CIGARETTE SMOKERS

This is a double-blind, placebo controlled intervention trial using biologic markers to evaluate whether supplementation with antioxidant micronutrients will lower DNA damage in a cohort of 300 current cigarette smokers. Further, the study will also evaluate whether genetic factors modulate the effects on micronutrients. Study subjects will be recruited and randomized into placebo or vitamin treatment groups. The latter will receive 400 IU vitamin E, and 500 mg vitamin C, since experimental and epidemiologic data indicate that these micronutrients inhibit DNA damage and tumor formation. Biomarkers of DNA damage and plasma vitamin levels will be evaluated in blood samples drawn at baseline and at three-month intervals over one year of treatment and one year of follow-up. In addition, lipid profiles will be obtained at each time point. Each of the 300 subjects is followed over a two-year time period. Possible subjects are screened to determine eligibility based on current smoking, health status and his/her agreement to comply. Following the screening, each subject is scheduled for a baseline interview to complete an intial questionnaire eliciting demographic information. In addition, the subject must provide a 45 ml blood sample and a saliva sample with buccal cells for analysis. Those enrolled receive placebo pills for the first month of enrollment in the study and the initial baseline blood sample is then tested for biochemical abnormalities in liver function to determine if the subject is still eligible for the study. In the subsequent one-month visit, each subject is informed of any abnormalities with the suggestion that his/her physician be contacted. If the subject continues to be eligible for the study, he/she is randomized and assigned to take either the placebo or vitamin supplement (400IU of a-tocopherol and 500 mg of vitamin C) with the request that they return at 3,6,9 and 12 months for serial blood and buccal cell samples. At each follow-up interview, subjects are required to complete a one-page exposure questionnaire administered by the interviewer. Upon completion of the vitamin/placebo treatment phase at 12 months of enrollment, each subject is then given placebo for an additional 12 months to determine the duration of any vitamin-derived benefits. The subjects remain blinded throughout the 24-month study. Subjects continue to return at 15,18,21 and 24 months for a blood drawing, buccal cell sample and exposure questionnaires. Dietary questionnaires are administered at randomization and at the 15 month visit.