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Low fruit consumption and folate deficiency are associated with LINE-1 hypomethylation in women of a cancer-free population.

ABSTRACT: Several dietary agents, such as micronutrient and non-nutrient components, the so-called bioactive food components, have been shown to display anticancer properties and influence genetic processes. The most common epigenetic change is DNA methylation. Hypomethylation of long interspersed elements (LINE-1) has been associated with an increased risk of several cancers, although conflicting findings have also been observed. The aim of the present study was to test the hypothesis that a low adherence to the Mediterranean diet (MD) and folate deficiency may cause LINE-1 hypomethylation in blood leukocytes of healthy women, and thus genomic instability. One hundred and seventy-seven non-pregnant women were enrolled. Mediterranean diet score (MDS) and folate intake were calculated using a food frequency questionnaire. LINE-1 methylation level was measured by pyrosequencing analysis in three CpG sites of LINE-1 promoter. According to MDS, only 9.6 % of subjects achieved a high adherence to MD. Taking into account the use of supplements, there was a high prevalence of folate deficiency (73.4 %). Women whose consumption of fruit was below the median value (i.e., <201 gr/day) were 3.7 times more likely to display LINE-1 hypomethylation than women whose consumption was above the median value (OR 3.7; 95 % CI 1.4-9.5). Similarly, women with folate deficiency were 3.6 times more likely to display LINE-1 hypomethylation than women with no folate deficiency (OR 3.6; 95 % CI 1.1-12.1). A dietary pattern characterized by low fruit consumption and folate deficiency is associated with LINE-1 hypomethylation and with cancer risk.

SUBMITTER: Agodi A

PROVIDER: S-EPMC4504850 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Low fruit consumption and folate deficiency are associated with LINE-1 hypomethylation in women of a cancer-free population.

Agodi Antonella A Barchitta Martina M Quattrocchi Annalisa A Maugeri Andrea A Canto Carolina C Marchese Anna Elisa AE Vinciguerra Manlio M

Genes & nutrition 20150717 5

Several dietary agents, such as micronutrient and non-nutrient components, the so-called bioactive food components, have been shown to display anticancer properties and influence genetic processes. The most common epigenetic change is DNA methylation. Hypomethylation of long interspersed elements (LINE-1) has been associated with an increased risk of several cancers, although conflicting findings have also been observed. The aim of the present study was to test the hypothesis that a low adherenc ...[more]

PMID: 26183162

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Project description:BackgroundCadmium, a common food pollutant, alters DNA methylation in vitro. Epigenetic effects might therefore partly explain cadmium's toxicity, including its carcinogenicity; however, human data on epigenetic effects are lacking.ObjectiveWe evaluated the effects of dietary cadmium exposure on DNA methylation, considering other environmental exposures, genetic predisposition, and gene expression.MethodsConcentrations of cadmium, arsenic, selenium, and zinc in blood and urine of nonsmoking women (n = 202) from the northern Argentinean Andes were measured by inductively coupled mass spectrometry. Methylation in CpG islands of LINE-1 (long interspersed nuclear element-1; a proxy for global DNA methylation) and promoter regions of p16 [cyclin-dependent kinase inhibitor 2A (CDKN2A)] and MLH1 (mutL homolog 1) in peripheral blood were measured by bisulfite polymerase chain reaction pyrosequencing. Genotyping (n = 172) for the DNA (cytosine-5-)-methyltransferase 1 gene (DNMT1 rs10854076 and rs2228611) and DNA (cytosine-5-)-methyltransferase 3 beta gene (DNMT3B rs2424913 and rs2424932) was performed with Sequenom iPLEX GOLD SNP genotyping; and gene expression (n = 90), with DirectHyb HumanHT-12 (version 3.0).ResultsCadmium exposure was low: median concentrations in blood and urine were 0.36 and 0.23 µg/L, respectively. Urinary cadmium (natural log transformed) was inversely associated with LINE-1 methylation (β = -0.50, p = 0.0070; β = -0.44, p = 0.026, adjusted for age and coca chewing) but not with p16 or MLH1 methylation. Both DNMT1 rs10854076 and DNMT1 rs2228611 polymorphisms modified associations between urinary cadmium and LINE-1 (p-values for interaction in adjusted models were 0.045 and 0.064, respectively). The rare genotypes demonstrated stronger hypomethylation with increasing urinary cadmium concentrations. Cadmium was inversely associated with DNMT3B (r(S) = -0.28, p = 0.0086) but not with DNMT1 expression (r(S) = -0.075, p = 0.48).ConclusionEnvironmental cadmium exposure was associated with DNA hypomethylation in peripheral blood, and DNMT1 genotypes modified this association. The role of epigenetic modifications in cadmium-associated diseases needs clarification.

Project description:BackgroundFolate deficiency (FD) can cause adverse health outcomes of public health significance. Although FD is a significant micronutrient deficiency in Ethiopia, concrete evidence is limited. Therefore, this systematic review and meta-analysis was designed to estimate the pooled prevalence of FD among women of reproductive age (WRA).MethodsA systematic literature search was performed using MEDLINE, Embase, CINAHL, Google Scholar, African Journals Online (AJOL), The Vitamin and Mineral Nutrition Information System (VMNIS) of the World Health Organization (WHO), Global Health Data Exchange (GHDx), and institutional repositories of major universities and research centers. Additionally, we scanned the reference lists of relevant articles. Two authors independently selected the studies, extracted the data, and the study risk of bias. Heterogeneity was assessed using the I2 statistic. We used a random-effects model to estimate the pooled mean serum/plasma folate and the pooled prevalence of FD. Begg's and Egger's tests were used to check publication bias.ResultsTen studies-nine cross-sectional and one case-control-with a total of 5,623 WRA were included in the systematic review and meta-analysis. Four (WRA = 1,619) and eight (WRA = 5,196) cross-sectional studies were used to estimate the pooled mean serum/plasma folate and prevalence of FD, respectively. The pooled mean serum/plasma folate concentration estimate was 7.14 ng/ml (95% CI: 5.73, 8.54), and the pooled prevalence of FD was estimated to be 20.80% (95% CI: 11.29, 32.27). In addition the meta-regression analysis showed that the sampling technique was significantly associated with mean serum/plasma folate concentration.ConclusionsFD is a significant public health issue among WRA in Ethiopia. Therefore, the public health strategies of the country should focus on promoting the consumption of folate-rich foods, strengthening the coverage of folic acid supplementation and its adherence, and swift translation of the mandatory folic acid fortification into action.Systematic review registrationPROSPERO 2022-CRD42022306266.

Dataset Information

Low fruit consumption and folate deficiency are associated with LINE-1 hypomethylation in women of a cancer-free population.

Publications

Low fruit consumption and folate deficiency are associated with LINE-1 hypomethylation in women of a cancer-free population.

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