MTHFR polymorphisms, folate intake and carcinogen DNA adducts in the lung

Authors

  • Mi-Sun Lee,

    1. Department of Environmental Health, Environmental and Occupational Medicine and Epidemiology Program, Harvard School of Public Health, Boston, MA
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  • Kofi Asomaning,

    1. Department of Environmental Health, Environmental and Occupational Medicine and Epidemiology Program, Harvard School of Public Health, Boston, MA
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  • Li Su,

    1. Department of Environmental Health, Environmental and Occupational Medicine and Epidemiology Program, Harvard School of Public Health, Boston, MA
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  • John C. Wain,

    1. Thoracic Surgery Unit, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA
    2. Pathology Department, Massachusetts General Hospital/Harvard Medical School, Boston, MA
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  • Eugene J. Mark,

    1. Pathology Department, Massachusetts General Hospital/Harvard Medical School, Boston, MA
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  • David C. Christiani

    Corresponding author
    1. Department of Environmental Health, Environmental and Occupational Medicine and Epidemiology Program, Harvard School of Public Health, Boston, MA
    2. Pulmonary and Critical Care Unit/Department of Medicine, Massachusetts General Hospital/Harvard Medical School, Boston, MA
    • Department of Environmental Health, Environmental and Occupational Medicine and Epidemiology Program, Harvard School of Public Health, 665 Huntington Ave, Building I Room 1401, Boston, MA 02115, USA
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    • Tel.: 617-432-3323, Fax: 617-432-3441


Abstract

The methylenetetrahydrofolate reductase (MTHFR) genes and folate in one-carbon metabolism are essential for DNA methylation and synthesis. However, their role in carcinogen DNA damage in target lung tissue, a dosimeter for cancer risk, is not known. Our study aimed to investigate the association between genetic and nutritional one-carbon metabolism factors and DNA adducts in target lung. Data on 135 lung cancer cases from the Massachusetts General Hospital were studied. Genotyping was completed for MTHFR C677T (rs1801133) and A1298C (rs1801131). Information on dietary intake for one-carbon related micronutrients, folate and other B vitamin was derived from a validated food frequency questionnaire. DNA adducts in lung were measured by 32P-postlabeling. After adjusting for potential confounders, DNA adduct levels in lung significantly increased by 69.2% [95% confidence interval (CI), 5.5% to 171.5%] for the MTHFR 1298AC+CC genotype. The high risk group, combining the A1298C (AC+CC) plus C677T (CT+TT) genotypes, had significantly enhanced levels of lung adducts by 210.7% (95% CI, 21.4% to 695.2%) in contrast to the A1298C (AA) plus C677T (CC) genotypes. Elevation of DNA adduct was pronounced—111.3% (95% CI, −3.0 to 360.5%) among 1298AC+CC patients, who consumed the lowest level of folate intake as compared to 1298AA individuals with highest tertile of intake. These results indicate that DNA adducts levels are influenced by MTHFR polymorphisms and low folate consumption, suggesting an important role of genetic and nutritional factors in protecting DNA damage from lung carcinogen in at-risk populations.

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