Carcinogenesis, Vol 18, 503-509, Copyright © 1997 by Oxford University Press
LA Mooney, DA Bell, RM Santella, AM Van Bennekum, R Ottman, M Paik, WS Blaner, GW Lucier, L Covey, TL Young, TB Cooper, AH Glassman and FP Perera
Prior epidemiological evidence suggests that genes controlling the
metabolism of carcinogens and antioxidant/nutritional status are associated
with lung cancer risk, possibly through their ability to modulate DNA
damage by carcinogens. We performed a cross-sectional analysis of 159 heavy
smokers from a cohort of subjects enrolled in a smoking cessation program.
A total of 159 blood samples were analyzed to determine the relative
contributions of genetic polymorphisms [CYP1A1 MspI and exon 7 and
glutathione S-transferase M1 (GSTM1)] and plasma micronutrients to
polycyclic aromatic hydrocarbon-DNA (PAH-DNA) adduct levels. DNA damage in
smokers was affected by genetic polymorphisms and nutritional status.
Smokers with the CYP1A1 exon 7 valine polymorphism had significantly higher
(2-fold, P < or = 0.03) levels of DNA damage than those without. In
parallel models, PAH-DNA adducts were inversely associated with plasma
levels of retinol (beta = -0.93, P = 0.01), beta-carotene (beta = -0.18, P
= 0.09), and alpha- tocopherol (beta = -0.28, P = 0.21) in 159 subjects.
The association between smoking-adjusted plasma beta-carotene levels and
DNA damage was only significant in those subjects lacking the GSTM1
detoxification gene (beta = -0.30, P = 0.05, n = 75). There was a
statistical interaction between beta-carotene and alpha-tocopherol; when
beta- carotene was low, alpha-tocopherol had a significant protective
effect (beta = -0.78, P = 0.04) on adducts, but not when beta-carotene was
high (beta = -0.16, P = 0.57). Plasma alpha-tocopherol was significantly
correlated with beta-carotene (r = 0.36, P = 0.0005) and less strongly with
retinol (r = 0.20, P = 0.0005). These results suggest that several
micronutrients may act in concert to protect against DNA damage and
highlight the importance of assessing overall antioxidant status. In
conclusion, a subset of smokers may be at increased risk of DNA damage and
possibly lung cancer due to the combined effect of low plasma
micronutrients and genetic susceptibility factors. The use of biological
markers to assess efficacy of interventions and to study mechanisms of
micronutrients is timely given the current debate regarding the use of
chemopreventive agents in high risk populations.
ARTICLES
Contribution of genetic and nutritional factors to DNA damage in heavy smokers
Columbia University School of Public Health, Division of Environmental Health Sciences, New York, NY 10032, USA.
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