High levels of circulating folate concentrations are associated with DNA methylation of tumor suppressor and repair genes p16, MLH1, and MGMT in elderly Chileans
| Autor: | Cecilia Albala, Sandra Hirsch, Hugo Sánchez, Karin Broberg, Ana María Ronco, Mohammad Bakhtiar Hossain, Lydia Lera, Ricardo Uauy |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Tumor suppressor gene lcsh:QH426-470 DNA repair Tumor suppressor genes Population lcsh:Medicine Biology Epigenesis Genetic 03 medical and health sciences Folic Acid 0302 clinical medicine Folates Genetics Humans Cancer epigenetics Epigenetics Chile education DNA Modification Methylases Molecular Biology Cyclin-Dependent Kinase Inhibitor p16 Genetics (clinical) Aged Aged 80 and over education.field_of_study DNA methylation Research Tumor Suppressor Proteins lcsh:R Sequence Analysis DNA Methylation Vitamin B 12 lcsh:Genetics Cross-Sectional Studies DNA Repair Enzymes Long Interspersed Nucleotide Elements 030104 developmental biology CpG site 030220 oncology & carcinogenesis Cancer research Female MutL Protein Homolog 1 Developmental Biology |
| Zdroj: | Clinical Epigenetics, Vol 9, Iss 1, Pp 1-11 (2017) Clinical Epigenetics |
| ISSN: | 1868-7083 1868-7075 4815-3354 |
| DOI: | 10.1186/s13148-017-0374-y |
| Popis: | Changes in DNA methylation, one of the most studied epigenetic mechanisms, are considered an initial marker for early cancer detection. We evaluated how availability of dietary factors (folates and vitamin B12) involved in one-carbon metabolism may contribute to DNA methylation changes of cancer-related genes in human subjects. We studied, by pyrosequencing, the methylation of tumor suppressor gene p16, DNA repair genes MLH1 and MGMT, and the repetitive element LINE-1 (as a surrogate for global DNA methylation), in blood of elderly individuals (n = 249) who had been exposed to folic acid (FA) through FA-fortified wheat flour during the last 12 years. We found that serum folate and to a lesser extent, vitamin B12 concentrations, were significantly correlated with DNA methylation of p16, MLH1, and MGMT, but not with LINE-1. High serum folate concentrations (>45.3 nmol/L) were present in 31.1% of the participants. Although the methylated fraction of CpG sites in p16, MLH1, and MGMT was low (1.17–3.8%), high folate concentrations were significantly associated with methylation at the 3rd tertile of specific CpG sites in all genes with OR between 1.97 and 4.17. This study shows that a public policy, like food fortification with FA that increases circulating serum folate levels, could affect methylation levels of specific genes linked to cancer risk. Our present results deserve additional studies to clarify the real impact of high FA levels for risk of cancer in a whole population chronically exposed to a fortified food such as wheat flour. ISRCTN 48153354 and ISRCTN 02694183 |
| Databáze: | OpenAIRE |
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