Carcinogenesis Advance Access published online on April 24, 2003
Carcinogenesis, doi:10.1093/carcin/bgg064
© 2003 by Oxford University Press
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MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
1 Laboratory of Comparative Toxicology and Ecotoxicology, Istituto Superiore di Sanità, Rome, Italy
* Corresponding author. E-mail: zijno{at}iss.it.
Received 20 January 2003
; revised 9 April 2003
; accepted 10 April 2003
Gene-environment interactions play an important role in folate metabolism, with potential impact on human health. Deficiencies in the uptake of key micronutrients and variant genotypes can affect folic acid cycle, modulating methyl group transfer in key processes, and leading to increased cancer risk and Down syndrome incidence. So far, the significance of folate status and metabolic genotypes on baseline levels of DNA damage in normal individuals has not been fully elucidated. In this study, the possible modulation of SCE, micronuclei and tail moment values in peripheral lymphocytes by plasma levels of folic acid, homocysteine and vitamin B12, and by the methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms was investigated in 191 healthy subjects. The results obtained show a highly significant (p = 0.001) positive association between plasma levels of vitamin B12 and frequencies of both SCE and High Frequency Cells (HFC, above 90° percentile) in smokers. No significant effect was observed in non-smokers. Moreover, after correction for age, gender and GSTM1 genotype, a significant association (p = 0.026) between the MTRR 66GG variant genotype and higher micronucleus rates was observed. Tail moment values were not affected by any of the independent variables considered. Overall, the results obtained suggest that both folate status and relevant metabolic genotype can influence background levels of DNA damage in normal subjects. The significant association observed in smokers between plasma vitamin B12 and SCE frequencies may highlight the effect of methylation status on DNA damage and repair, although the role of other, unidentified dietary factors cannot be ruled out. At the same time, micronucleus data indicate that the MTRR 66GG variant may represent another individual trait of relative genomic instability, thus supporting epidemiological data on increased risk of Down syndrome conception in MTRR 66GG subjects.
folic acid, vitamin B12, homocysteine, SCE, micronuclei, comet assay, genetic polymorphism, methylenetetrahydrofolate reductase, methionine synthase reductase, tobacco smoke
Folate status, metabolic genotype, and biomarkers of genotoxicity in healthy subjects
2 Laboratory of Clinical Biochemistry, Istituto Superiore di Sanità, Rome, Italy
3 Istituto Regina Elena for Cancer Research, Rome
4 Department of Cellular Biotechnology and Haematology, Università "La Sapienza", Rome
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