Carcinogenesis, Vol. 24, No. 4, 739-746,
April 2003
© 2003 Oxford University Press
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION |
Biomarkers of dietary intake of micronutrients modulate DNA adduct levels in healthy adults
Molecular and Nutritional Epidemiology Unit and Cancer Risk Factor Branch, Molecular Biology Laboratory – Cspo, Scientific Institute of Tuscany, Florence
1 Cancer Epidemiology Unit, Cpo, Turin
2 Genetics Research Institute, Milan
3 Epidemiology Unit, Int, Milan
4 Department of Clinical and Experimental Medicine, Federico Ii University, Naples
5 Registro Tumori, A.O. ‘Civile-M.P. Arezzo’, Ragusa, Italy
6 Nutrition and Cancer Unit, IARC, Lyon, France
7To whom correspondence should be addressed Email: d.palli{at}cspo.it
DNA adducts, a reliable indicator of internal dose exposure to genotoxic agents and, possibly, of cancer risk, have been shown to be modulated by diet, particularly by the consumption of fresh fruit and vegetables, and by the intake of antioxidants (Palli et al., 2000, Int. J. Cancer, 87, 444–451). We have therefore investigated the association between DNA adducts in peripheral leukocytes and plasma levels of selected micronutrients, also taking into account the role of metabolic polymorphisms and smoking history, in a large independent random sample of volunteers enrolled in the prospective study EPIC–Italy (
110 subjects from each of the three main geographical study areas, Northern, Central and Southern Italy). DNA adducts and five polymorphic metabolic genotypes were determined in peripheral leukocytes using the 32P-post-labelling technique and PCR methods. Plasma levels of six carotenoids, retinol and 
- and 
-tocopherol were determined in the same blood sample. Among 331 subjects, 78.3% had detectable levels of DNA adducts (mean 7.46 ± 0.48 per 109 nucleotides). Vitamin supplementation was reported by only a few subjects (3.9%). Strong inverse associations emerged between levels of DNA adducts and plasma retinol (P = 0.02), -tocopherol (P = 0.04) and -tocopherol (P = 0.03), but not carotenoids (except a borderline inverse association with ß-carotene, P = 0.08). An inverse significant association with plasma levels of retinol and -tocopherol persisted in the subgroup of non-smokers, whereas a negative association with -tocopherol emerged only in smokers. DNA adduct levels did not show any significant variation according to analyzed genotypes. Stratification by GSTM1 genotype, however, showed a significant negative association between DNA adduct levels and plasma levels of - (P = 0.02) and ß-carotene (P = 0.02) in subjects with the GSTM1 null genotype. Our results confirm that biomarkers of dietary intake of antioxidants significantly modulate DNA adducts and suggest specific inverse associations between DNA adduct levels and antioxidant concentrations among GSTM1 null subjects and smokers.
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