Evidence map›Paper›PMID 30029654›Full record

ArticleJournal of translational medicine2018

In vivo evidence of ascorbate involvement in the generation of epigenetic DNA modifications in leukocytes from patients with colorectal carcinoma, benign adenoma and inflammatory bowel disease.

Marta Starczak, Ewelina Zarakowska, Martyna Modrzejewska, Tomasz Dziaman, Anna Szpila, Kinga Linowiecka, Jolanta Guz, Justyna Szpotan, Maciej Gawronski, Anna Labejszo and 6 more

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.8field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 39 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
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  5. Diet as an epigenetic factor in inflammatory bowel disease.World journal of gastroenterology · 2023
    Review
  6. Article
  7. Article
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  10. Review
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  14. Pathways of Gastric Carcinogenesis,International journal of molecular sciences · 2020
    Review
  15. Review
  16. Review
  17. Genome-Protecting Compounds as Potential Geroprotectors.International journal of molecular sciences · 2020
    Review
  18. Review
  19. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 1 institution in 1 country.

Marta StarczakDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Karlowicza 24, 85-092, Bydgoszcz, Poland.
Ewelina ZarakowskaDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Karlowicza 24, 85-092, Bydgoszcz, Poland.
Martyna ModrzejewskaDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Karlowicza 24, 85-092, Bydgoszcz, Poland.
Tomasz DziamanDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Karlowicza 24, 85-092, Bydgoszcz, Poland.
Anna SzpilaDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Karlowicza 24, 85-092, Bydgoszcz, Poland.
Kinga LinowieckaDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Karlowicza 24, 85-092, Bydgoszcz, Poland.
Jolanta GuzDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Karlowicza 24, 85-092, Bydgoszcz, Poland.
Justyna SzpotanDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Karlowicza 24, 85-092, Bydgoszcz, Poland.
Maciej GawronskiDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Karlowicza 24, 85-092, Bydgoszcz, Poland.
Anna LabejszoDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Karlowicza 24, 85-092, Bydgoszcz, Poland.
Ariel LiebertDepartment of Vascular Diseases and Internal Medicine, Faculty of Health Sciences, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Ujejskiego 75, 85-168, Bydgoszcz, Poland.
Zbigniew BanaszkiewiczDepartment of Vascular Surgery and Angiology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, M. Curie Sklodowskiej 9, 85-094, Bydgoszcz, Poland.
Maria KlopockaDepartment of Vascular Diseases and Internal Medicine, Faculty of Health Sciences, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Ujejskiego 75, 85-168, Bydgoszcz, Poland.
Marek FoksinskiDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Karlowicza 24, 85-092, Bydgoszcz, Poland.
Daniel GackowskiDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Karlowicza 24, 85-092, Bydgoszcz, Poland. danielg@cm.umk.pl.ORCID 0000-0002-7259-1511
Ryszard OlinskiDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Karlowicza 24, 85-092, Bydgoszcz, Poland. ryszardo@cm.umk.pl.
Nicolaus Copernicus University · PL

Funding

Narodowe Centrum Nauki 2013/09/B/NZ5/00767
6 · The paper itself

Abstract

backgroundA characteristic feature of malignant cells, such as colorectal cancer cells, is a profound decrease in the level of 5-hydroxymethylcytosine, a product of 5-methylcytosine oxidation by TET enzymes. Recent studies showed that ascorbate may upregulate the activity of TET enzymes in cultured cells and enhance formation of their products in genomic DNA.

methodsThe study included four groups of subjects: healthy controls (n = 79), patients with inflammatory bowel disease (IBD, n = 51), adenomatous polyps (n = 67) and colorectal cancer (n = 136). The list of analyzed parameters included (i) leukocyte levels of epigenetic DNA modifications and 8-oxo-7,8-dihydro-2'-deoxyguanosine, a marker of oxidatively modified DNA, determined by means of isotope-dilution automated online two-dimensional ultra-performance liquid chromatography with tandem mass spectrometry, (ii) expression of TET mRNA measured with RT-qPCR, and (iii) chromatographically-determined plasma concentrations of retinol, alpha-tocopherol and ascorbate.

resultsPatients from all groups presented with significantly lower levels of 5-methylcytosine and 5-hydroxymethylcytosine in DNA than the controls. A similar tendency was also observed for 5-hydroxymethyluracil level. Patients with IBD showed the highest levels of 5-formylcytosine and 8-oxo-7,8-dihydro-2'-deoxyguanosine of all study subjects, and individuals with colorectal cancer presented with the lowest concentrations of ascorbate and retinol. A positive correlation was observed between plasma concentration of ascorbate and levels of two epigenetic modifications, 5-hydroxymethylcytosine and 5-hydroxymethyluracil in leukocyte DNA. Moreover, a significant difference was found in the levels of these modifications in patients whose plasma concentrations of ascorbate were below the lower and above the upper quartile for the control group.

conclusionsThese findings suggest that deficiency of ascorbate in the blood may be a marker of its shortage in other tissues, which in turn may correspond to deterioration of DNA methylation-demethylation. These observations may provide a rationale for further research on blood biomarkers of colorectal cancer development.

Indexed as

AdenomaAgedalpha-TocopherolAscorbic AcidCase-Control StudiesColorectal NeoplasmsDNAEpigenesis, GeneticFemaleHumansInflammatory Bowel DiseasesLeukocytesMaleProto-Oncogene ProteinsRNA, MessengerVitamin Aalpha-TocopherolAscorbic AcidDNAProto-Oncogene ProteinsRNA, MessengerVitamin AAscorbateColon polypColorectal cancerDNA demethylationEpigenetic DNA modificationsIBD

Identifiers

PMID30029654
PMCPMC6053776
OpenAlexW2884732079

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.