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Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research v.26 no.2, 2017년, pp.261 - 269   SCI SCIE
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Sex-Specific Associations between One-Carbon Metabolism Indices and Posttranslational Histone Modifications in Arsenic-Exposed Bangladeshi Adults

Howe, Caitlin G. (Department of Environmental Health Sciences, Mailman School of Public Health, New York ) ; Liu, Xinhua (Department of Biostatistics, Mailman School of Public Health, New York. ) ; Hall, Megan N. (Department of Epidemiology, Mailman School of Public Health, New York. ) ; Ilievski, Vesna (Department of Environmental Health Sciences, Mailman School of Public Health, New York ) ; Caudill, Marie A. (Division of Nutritional Sciences, Cornell University, Ithaca, New York. ) ; Malysheva, Olga (Division of Nutritional Sciences, Cornell University, Ithaca, New York. ) ; Lomax-Luu, Angela M. (Department of Environmental Health Sciences, Mailman School of Public Health, New York ) ; Parvez, Faruque (Department of Environmental Health Sciences, Mailman School of Public Health, New York ) ; Siddique, Abu B. (Columbia University Arsenic Project in Bangladesh, Dhaka, Bangladesh. ) ; Shahriar, Hasan (Columbia University Arsenic Project in Bangladesh, Dhaka, Bangladesh. ) ; Uddin, Mohammad N. (Columbia University Arsenic Project in Bangladesh, Dhaka, Bangladesh. ) ; Islam, Tariqul (Columbia University Arsenic Project in Bangladesh, Dhaka, Bangladesh. ) ; Graziano, Joseph H. (Department of Environmental Health Sciences, Mailman School o ) ; Costa, Max ; Gamble, Mary V. ;
  • 초록  

    Background: Posttranslational histone modifications (PTHMs) are altered by arsenic, an environmental carcinogen. PTHMs are also influenced by nutritional methyl donors involved in one-carbon metabolism (OCM), which may protect against epigenetic dysregulation. Methods: We measured global levels of three PTHMs, which are dysregulated in cancers (H3K36me2, H3K36me3, H3K79me2), in peripheral blood mononuclear cells (PBMC) from 324 participants enrolled in the Folic Acid and Creatine Trial, a randomized trial in arsenic-exposed Bangladeshi adults. Sex-specific associations between several blood OCM indices (folate, vitamin B12, choline, betaine, homocysteine) and PTHMs were examined at baseline using regression models, adjusted for multiple tests by controlling for the false discovery rate ( P FDR ). We also evaluated the effects of folic acid supplementation (400 μg/d for 12 weeks), compared with placebo, on PTHMs. Results: Associations between choline and H3K36me2 and between vitamin B12 and H3K79me2 differed significantly by sex ( P diff < 0.01 and <0.05, respectively). Among men, plasma choline was positively associated with H3K36me2 ( P FDR < 0.05), and among women, plasma vitamin B12 was positively associated with H3K79me2 ( P FDR < 0.01). Folic acid supplementation did not alter any of the PTHMs examined ( P FDR = 0 0.80). Conclusions: OCM indices may influence PTHMs in a sex-dependent manner, and folic acid supplementation, at this dose and duration, does not alter PTHMs in PBMCs. Impact: This is the first study to examine the influences of OCM indices on PTHMs in a population that may have increased susceptibility to cancer development due to widespread exposure to arsenic-contaminated drinking water and a high prevalence of hyperhomocysteinemia. Cancer Epidemiol Biomarkers Prev; 26(2); 261–9. ©2016 AACR .


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