The influence of obesity on folate status, DNA methylation and cancer-related gene expression in normal breast tissues from premenopausal women

Frederick, Armina-Lyn M.; Guo, Chi; Meyer, Ann; Yan, Liying; Schneider, Sallie S.; Liu, Zhenhua

doi:10.1080/15592294.2020.1805687

Cited by 6 publications

(10 citation statements)

References 42 publications

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“…In another recent study by the authors, using mammary tissue from pre-menopausal women who underwent reduction mammoplasty, a positive association was confirmed between BMI and breast tissue folate levels, with an increase of 2.65 ng/g folate per every 5-unit increase in BMI (P<0.01) (41). Following this observation, the DNA methylation of LINE-1 was also found to be significantly associated with BMI (P<0.05) (41). These data indicates a novel mechanism responsible for the inverse association between obesity and pre-BC: Obesity exerts its protective effects against pre-BC by modifying folate metabolism and DNA methylation (Fig.…”

Section: Folate Metabolism In Obesity and Breast Cancermentioning

confidence: 82%

“…Based on the NHANES dataset, the authors' research group previously demonstrated (in 2015) that, despite a lower dietary intake, a high BMI is notably associated with an increased red blood cell folate level and this association is of particular significance for pre-menopausal women (126). In another recent study by the authors, using mammary tissue from pre-menopausal women who underwent reduction mammoplasty, a positive association was confirmed between BMI and breast tissue folate levels, with an increase of 2.65 ng/g folate per every 5-unit increase in BMI (P<0.01) (41). Following this observation, the DNA methylation of LINE-1 was also found to be significantly associated with BMI (P<0.05) (41).…”

Section: Folate Metabolism In Obesity and Breast Cancermentioning

confidence: 88%

“…However, the mechanisms responsible for the associations between obesity and pre-BC are less understood, and a recent study by the authors demonstrated a potential epigenetic mechanism: Obesity influences folate metabolism and leads to an elevation in breast tissue folate levels, preventing the development of pre-BC by altering global methylation (41). Further details on this matter are discussed below, as well as in the previous study (41).…”

mentioning

confidence: 92%

“…A number of studies have been conducted in order to understand the positive association between obesity and post-BC, and several mechanisms governing this association have been proposed and defined, including adipose tissue-driving circulating hormones and an obesity-associated chronic low-grade inflammatory state (12,40). However, the mechanisms responsible for the associations between obesity and pre-BC are less understood, and a recent study by the authors demonstrated a potential epigenetic mechanism: Obesity influences folate metabolism and leads to an elevation in breast tissue folate levels, preventing the development of pre-BC by altering global methylation (41). Further details on this matter are discussed below, as well as in the previous study (41).…”

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confidence: 99%

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Paradoxical effects of obesity on pre‑ vs. post‑menopausal breast cancer: The epigenetic mechanisms (Review)

2021

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Breast cancer (BC) has surpassed lung cancer as the most commonly diagnosed cancer among women in the US, as well as globally. A number of factors evidently contribute to the risk of developing BC, including age, physical activity, overweight/obesity, alcohol consumption, etc. It is of particular importance to study the role of body fatness and its potential influence on the risk of developing BC, as the number of individuals with obesity has increased with an alarming rate worldwide in recent decades. Epigenetics alterations are reversible, and do not alter the DNA sequence; however, they can affect gene expression via modifiable factors, including lifestyle and environmental factors. The present review article, in addition to providing overall reviews of obesity and BC in association with public health, concentrated on the epigenetic phenomena, with a focus on the well-studied DNA methylation, and its role in the association between obesity and BC. The present review aimed to provide insight into the understanding of the paradoxical effects of obesity on pre-vs. post-menopausal BC (pre-BC vs. post-BC), and describe the mechanisms through which folate metabolism/DNA methylation may be responsible for the protective effects of obesity on pre-BC. The literature presented in the present review article indicates that the epigenetic alterations represent a mediator in the association between obesity and BC; however, the mechanisms through which obesity differentially affects pre-vs. post-BC remain unclear. Further studies using animal models and the analyses of human tissue biopsies are thus required to delineate the paradoxical effects of obesity on BC. Contents1. Obesity and breast cancer 2. Epigenetic alterations in breast cancer 3. Obesity and DNA methylation 4. Obesity, DNA methylation and breast cancer 5. Folate metabolism in obesity and breast cancer 6. Conclusions and future perspectives Obesity and breast cancerPrevalence of breast cancer (BC). BC has surpassed lung cancer as the most commonly diagnosed type of cancer among women, with ~2.26 million new cases and ~685,000 deaths recorded globally in 2020. These numbers represent 24.5% of all new cancer cases and 15.5% of cancer-attributed mortality in women, respectively (1). In the US, the new cases of BC have also markedly increased, reaching top levels among all new cancer cases among women, with ~282,000 cases estimated in 2021 (30%); BC also represents the 2nd leading cause of cancer-related mortality, with 43,600 deaths (15%), coming only second following lung cancer (2).The BC incidence rates have consistently increased during the decades between 1970-2000 in a number of industrialized countries, likely reflecting changes in lifestyle associated with civilization and increased detection via mammographic screening. In the 2000s, the incidence rates had reached a

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Section: Folate Metabolism In Obesity and Breast Cancermentioning

confidence: 82%

Section: Folate Metabolism In Obesity and Breast Cancermentioning

confidence: 88%

mentioning

confidence: 92%

mentioning

confidence: 99%

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Paradoxical effects of obesity on pre‑ vs. post‑menopausal breast cancer: The epigenetic mechanisms (Review)

2021

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“…Obesity‐associated reprogramming of the epigenome via DNA methylation may alter the expression of genes that promote or inhibit tumor progression 18 . Frederick et al showed that obesity played a protective role against premenopausal breast tumorigenesis by increasing Line ‐ 1 DNA methylation level and expression of tumor suppressor gene SFRP1 in breast tissues 19 . Nagashima et al reported that the dysregulation of DNA methylation in endometrial epithelial cells resulted in endometrial cancer development in women with obesity 20 .…”

Section: Introductionmentioning

confidence: 99%

DNA methylome analysis identifies BMI‐related epigenetic changes associated with non‐small cell lung cancer susceptibility

Meng

Bai

et al. 2021

Cancer Medicine

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Background Body mass index (BMI) has been reported to be inversely associated with incident risk of non‐small cell lung cancer (NSCLC). However, the underlying mechanism is still unclear. This study aimed to investigate the role of DNA methylation in the relationship between BMI and NSCLC. Methods We carried out a genome‐wide DNA methylation study of BMI in peripheral blood among 2266 Chinese participants by using Illumina Methylation arrays. For the BMI‐related DNA methylation changes, their associations with NSCLC risk were further analyzed and their mediation effects on BMI‐NSCLC association were also evaluated. Results The methylation levels of four CpGs (cg12593793, cg17061862, cg11024682, and cg06500161, annotated to LMNA, ZNF143, SREBF1, and ABCG1, respectively) were found to be significantly associated with BMI. Methylation levels of cg12593793, cg11024682, and cg06500161 were observed to be inversely associated with NSCLC risk [OR (95%CI) =0.22 (0.16, 0.31), 0.39 (0.30, 0.50), and 0.66 (0.53, 0.82), respectively]. Additionally, cg11024682 in SREBF1 and cg06500161 in ABCG1 mediated 45.3% and 19.5% of the association between BMI and decreased NSCLC risk, respectively. Conclusions In this study, we identified four DNA methylation sites associated with BMI in the Chinese populations at the genome‐wide significant level. We also found that the BMI‐related methylations of SREBF1 and ABCG1 could mediate about a quintile‐to‐half of the effect of BMI on reduced NSCLC risk, which adds a potential mechanism underlying this association.

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Epigenetic modifications in obesity‐associated diseases

Long,

Mao,

Liu

et al. 2024

MedComm

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The global prevalence of obesity has reached epidemic levels, significantly elevating the susceptibility to various cardiometabolic conditions and certain types of cancer. In addition to causing metabolic abnormalities such as insulin resistance (IR), elevated blood glucose and lipids, and ectopic fat deposition, obesity can also damage pancreatic islet cells, endothelial cells, and cardiomyocytes through chronic inflammation, and even promote the development of a microenvironment conducive to cancer initiation. Improper dietary habits and lack of physical exercise are important behavioral factors that increase the risk of obesity, which can affect gene expression through epigenetic modifications. Epigenetic alterations can occur in early stage of obesity, some of which are reversible, while others persist over time and lead to obesity‐related complications. Therefore, the dynamic adjustability of epigenetic modifications can be leveraged to reverse the development of obesity‐associated diseases through behavioral interventions, drugs, and bariatric surgery. This review provides a comprehensive summary of the impact of epigenetic regulation on the initiation and development of obesity‐associated cancers, type 2 diabetes, and cardiovascular diseases, establishing a theoretical basis for prevention, diagnosis, and treatment of these conditions.

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The influence of obesity on folate status, DNA methylation and cancer-related gene expression in normal breast tissues from premenopausal women

Cited by 6 publications

References 42 publications

Paradoxical effects of obesity on pre‑ vs. post‑menopausal breast cancer: The epigenetic mechanisms (Review)

Paradoxical effects of obesity on pre‑ vs. post‑menopausal breast cancer: The epigenetic mechanisms (Review)

DNA methylome analysis identifies BMI‐related epigenetic changes associated with non‐small cell lung cancer susceptibility

Epigenetic modifications in obesity‐associated diseases

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