Associations between genetic variation in one-carbon metabolism and LINE-1 DNA methylation in histologically normal breast tissues
| Autor: | Jo L. Freudenheim, Joel B. Mason, Zhenhua Liu, Scott L. Spear, Ramona G. Dumitrescu, Adana A.M. Llanos, Bhaskar Kallakury, Peter G. Shields, Theodore M. Brasky, Kepher H. Makambi, Catalin Marian |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Cancer Research Physiology Breast Neoplasms Single-nucleotide polymorphism Biology 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase Polymorphism Single Nucleotide Folic Acid Breast cancer Risk Factors medicine Humans Genetic Predisposition to Disease Breast Allele Molecular Biology Alleles Methylenetetrahydrofolate Reductase (NADPH2) Cancer Methylation DNA Methylation medicine.disease Molecular biology MTRR Carbon Ferredoxin-NADP Reductase Long Interspersed Nucleotide Elements DNA methylation Female Erratum Research Paper DNA hypomethylation |
| Zdroj: | Epigenetics. 10:727-735 |
| ISSN: | 1559-2308 1559-2294 |
| Popis: | Genome-wide DNA hypomethylation is an early event in the carcinogenic process. Percent methylation of long interspersed nucleotide element-1 (LINE-1) is a biomarker of genome-wide methylation and is a potential biomarker for breast cancer. Understanding factors associated with percent LINE-1 DNA methylation in histologically normal tissues could provide insight into early stages of carcinogenesis. In a cross-sectional study of 121 healthy women with no prior history of cancer who underwent reduction mammoplasty, we examined associations between plasma and breast folate, genetic variation in one-carbon metabolism, and percent LINE-1 methylation using multivariable regression models (adjusting for race, oral contraceptive use, and alcohol use). Results are expressed as the ratio of LINE-1 methylation relative to that of the referent group, with the corresponding 95% confidence intervals (CI). We found no significant associations between plasma or breast folate and percent LINE-1 methylation. Variation in MTHFR, MTR, and MTRR were significantly associated with percent LINE-1 methylation. Variant allele carriers of MTHFR A1289C had 4% lower LINE-1 methylation (Ratio 0.96, 95% CI 0.93-0.98), while variant allele carriers of MTR A2756G (Ratio 1.03, 95% CI 1.01-1.06) and MTRR A66G (Ratio 1.03, 95% CI 1.01-1.06) had 3% higher LINE-1 methylation, compared to those carrying the more common genotypes of these SNPs. DNA methylation of LINE-1 elements in histologically normal breast tissues is influenced by polymorphisms in genes in the one-carbon metabolism pathway. Future studies are needed to investigate the sociodemographic, environmental and additional genetic determinants of DNA methylation in breast tissues and the impact on breast cancer susceptibility. |
| Databáze: | OpenAIRE |
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