Antioxidant vitamin supplementation reduces benzo(a)pyrene-DNA adducts and potential cancer risk in female smokers.

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

Jan 2005

DOI: 10.1158/1055-9965.237.14.1

Citations:84

Influential Citations:4

Interventional (Human) Studies

Low RoB

Enhanced Details

Methods

Population: adults >18 years who smoked ≥10 cigarettes per day; both genders; no history of cancer or liver disease; not taking vitamin supplements; cotinine >25 ng/mL at baseline. Study design: randomized, double-blind, placebo-controlled clinical trial with 15-month follow-up; randomization stratified by gender and cigarettes per day (≤20 vs >20 CPD). Conducted at Columbia-Presbyterian Medical Center. Baseline and follow-up measures included B(a)P-DNA adducts in leukocytes; 373 attended baseline, 309 eligible, 284 randomized, 176 completed 15 months.

Intervention

Daily intake of a combination pill containing vitamin C 500 mg and vitamin E 400 IU for 15 months; one pill taken daily.

Results

Overall, vitamin C and E did not significantly reduce B(a)P-DNA adducts (14% reduction; P=0.19). In women, adducts were 31% lower in the vitamin group after adjusting for pretreatment adducts and cotinine (P=0.04); among GSTM1-null women, reduction was 43% (P=0.04). No significant effect in men or GSTM1-normal groups. Implication: antioxidant vitamins may reduce tobacco-related DNA damage in female smokers, especially GSTM1-null, but findings are not conclusive for clinical cancer risk; smoking cessation remains the primary strategy to lower cancer risk; confirmatory studies are needed.

Limitations

Small subgroup sample sizes (women, GSTM1-null); 15-month follow-up with 176/284 completers; DNA adducts measured in peripheral blood leukocytes rather than lung tissue; potential selection bias due to dropout; limited generalizability to low-income smoker populations; cancer outcomes not assessed.

Abstract

BACKGROUND Elevated benzo(a)pyrene [B(a)P]-DNA adducts have been associated with 3-fold increased risk of lung cancer in current smokers. We assessed the chemopreventive effects of antioxidant supplementation using B(a)P-DNA adducts in leukocytes as an intermediate cancer risk marker. METHODS Subjects were randomized to a double-blinded placebo-controlled clinical trial of antioxidant vitamin supplementation [500 mg vitamin C and 400 IU vitamin E (dl-alpha-tocopherol) daily] or placebo. Smokers with > or =10 cigarettes per day and serum cotinine > or =25 ng/mL were eligible for the study. B(a)P-DNA adduct level was the outcome. The randomization was stratified by gender and cigarettes per day (< or =20 or >20). Smoking habits and blood samples were collected every 3 months during the 15-month treatment period. Samples were analyzed for B(a)P-DNA adducts (high-performance liquid chromatography), plasma cotinine, vitamin levels, and GSTM1 genotype. The intent-to-treat model adjusted for B(a)P-DNA and cotinine at randomization. RESULTS Overall and among men, there was no effect of treatment on B(a)P-DNA adduct levels. Among treated women, B(a)P-DNA adducts decreased by 31% compared with women on placebo (P = 0.03). Among treated women with the GSTM1 genotype, there was a 43% decrease in adducts (P = 0.04). CONCLUSION Our primary hypothesis that the mean level of smoking-related B(a)P-DNA adducts would be lower in all subjects in the vitamin treatment group compared with all placebo-treated subjects was not substantiated. However, oursecondary gender-specific analysis found a significant reduction in B(a)P-DNA adducts in women with vitamin treatment, suggesting that antioxidant supplementation maymitigate some of the procarcinogenic effects of exposuretoB(a)P. The effect in GSTM1-null women suggeststhat certain subgroups may derive more benefit fromsupplementation. Although the results of this trial showthe potential chemopreventive role of antioxidants, thebest way for smokers to reduce their cancer risk remains smoking cessation. show less