Supplementary Table S1. Baseline characteristics of FACT participants with vs. without PTHM measures;Supplementary Table S2. Baseline characteristics of FACT participants with vs. without RBC folate measures; Supplementary Table S3. Associations (β (95% CI)) between OCM indices and PTHMs by sex in FACT participants, comparing models additionally adjusting for BMI; Supplementary Table S4. Associations (β (95% CI)) between OCM indices and PTHMs by sex in FACT participants, comparing models additionally adjusting for blood arsenic; Supplementary Table S5. Associations (β (95% CI))a between OCM indices and PTHMs by sex in FACT participants, comparing nutrients in model alone vs. included simultaneously;Supplementary Table S6. Associationsa between plasma OCM indices and PTHMs stratified by age and sex;Supplementary Table S7. Associationsa between plasma OCM indices and PTHMs stratified by blood arsenic and sex; Supplementary Table S8. Associationsa between changes in OCM indices and changes in PTHMs from baseline to week 12; Supplementary Figure S1. Sex-Specific Associations between OCM Indices and PTHMs in FACT Participants with RBC Folate Measures
ARTICLE ABSTRACT
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 (PFDR). 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 (Pdiff < 0.01 and <0.05, respectively). Among men, plasma choline was positively associated with H3K36me2 (PFDR < 0.05), and among women, plasma vitamin B12 was positively associated with H3K79me2 (PFDR < 0.01). Folic acid supplementation did not alter any of the PTHMs examined (PFDR = 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.
