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Association between serum 25-hydroxyvitamin D and global DNA methylation in visceral adipose tissue from colorectal cancer patients

Authors: Daniel Castellano-Castillo; Sonsoles Morcillo; Ana B. Crujeiras; Lidia Sánchez-Alcoholado; Mercedes Clemente-Postigo; Esperanza Torres; Francisco José Tinahones; +1 Authors

Association between serum 25-hydroxyvitamin D and global DNA methylation in visceral adipose tissue from colorectal cancer patients

Abstract

Visceral adipose tissue (VAT) has been identified as the essential fat depot for pathogenetic theories that associateobesity and colon cancer. LINE-1 hypomethylation has been mostly detected in tumor colon tissue, but less is known about the epigenetic pattern in surrounding tissues. The aim was to analyze for the first time the potential relationship between serum vitamin D, obesity and global methylation (LINE-1) in the visceral adipose tissue (VAT) from patients with and without colorectal cancer.A total of 55 patients with colorectal cancer and 35 control subjects participated in the study. LINE-1 DNA methylation in VAT was measured by pyrosequencing. Serum 25(OH)D levels were determined by ELISA.Cancer patients had lower levels of LINE-1 methylation in VAT compared with the control group. In the subjects with colorectal cancer, LINE-1 DNA methylation levels were associated positively with vitamin D levels (r = 0,463; p < 0.001) and negatively with BMI (r = - 0.334, p = 0.01) and HOMA insulin resistance index (r = - 0.348, p = 0.01). Serum vitamin D was the main variable explaining the LINE-1% variance in the cancer group (β = 0.460, p < 0.001). In a multivariate analysis, subjects with higher LINE-1 methylation values had lower risk of developing colorectal cancer (OR = 0.53; IC95% =0.28-0.99) compared with the control group.We showed for the first time an association between LINE-1 DNA methylation in VAT and vitamin D levels in subjects with colorectal cancer, highlighting the importance of VAT from cancer patients, which could be modified epigenetically compared to healthy subjects.

Keywords

Medical Subject Headings::Anatomy::Tissues::Connective Tissue::Adipose Tissue::Adipose Tissue, White::Abdominal Fat::Intra-Abdominal Fat, Male, Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms, Vitamina D, Obesidad, Enzyme-Linked Immunosorbent Assay, Medical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity, Intra-Abdominal Fat, Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans, Neoplasias colorrectales, Humans, Medical Subject Headings::Chemicals and Drugs::Polycyclic Compounds::Steroids::Secosteroids::Vitamin D, Obesity, Vitamin D, RC254-282, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Interspersed Repetitive Sequences::Retroelements::Long Interspersed Nucleotide Elements, Aged, Global DNA methylation, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Epigenetic, Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, DNA, Medical Subject Headings::Check Tags::Female, Sequence Analysis, DNA, DNA Methylation, Middle Aged, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA Methylation, Colorectal cancer, Medical Subject Headings::Check Tags::Male, Long Interspersed Nucleotide Elements, Medical Subject Headings::Persons::Persons::Age Groups::Adult::Aged, Epigenómica, Multivariate Analysis, Female, Enzyme-Linked Immunosorbent Assay|Aged, Colorectal Neoplasms, Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Molecular Probe Techniques::Immunoassay::Immunoenzyme Techniques::Enzyme-Linked Immunosorbent Assay, Epigénesis genética, Nucleotide Elements, Metilación de ADN, Research Article

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
20
Top 10%
Average
Top 10%
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