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Licensed Unlicensed Requires Authentication Published by De Gruyter November 8, 2022

Association of circulating free and total oxysterols in breast cancer patients

  • Nina Sophia Decker ORCID logo , Theron Johnson ORCID logo , Sabine Behrens , Nadia Obi , Rudolf Kaaks , Jenny Chang-Claude and Renée Turzanski Fortner ORCID logo EMAIL logo

Abstract

Objectives

Oxysterols, a family of oxidized cholesterol derivates, are of increasing interest due to their role in cancer development and progression. Some oxysterols are estrogen receptor modulators and thus of particular interest in breast cancer research. In human studies, two forms of circulating oxysterols are commonly evaluated: “free” (unesterified) and “total” (esterified and unesterified). However, associations between free and total oxysterols are not well established. We addressed this knowledge gap in a pilot study by evaluating correlations between the free and the total form of each of the circulating oxysterols (free vs. total), and pairwise associations within the panel of total oxysterols (total vs. total) and the panel of free oxysterols (free vs. free).

Methods

Concentrations of oxysterols and other non-cholesterol sterols were quantified in blood samples of 27 breast cancer patients from the MARIE breast cancer patient cohort using liquid chromatography mass spectrometry. We used Spearman rank correlations to assess associations. Overall, 12 oxysterols (including 27-hydroxycholesterol (HC), 25-HC, 24S-HC, 7a-HC, 5a6a-epoxycholesterol) and five sterols (including lanosterol and desmosterol) were analyzed.

Results

Strong correlations (r≥0.82) were observed for seven circulating free and total oxysterols/sterols. The free and total form of 27-HC (r=0.63), 25-HC (r=0.54), and two more oxysterols were weaker correlated. Correlation patterns in the panel of total oxysterols/sterols and the panel of free oxysterols/sterols were similar.

Conclusions

These findings demonstrate that concentrations of most free and total oxysterols/sterols are strongly correlated. We provide further insight into the interrelationships between oxysterols in breast cancer patients.


Corresponding author: Dr. Renée Turzanski Fortner, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; and Cancer Registry of Norway, Ullernchausseen 64, 0379 Oslo, Norway, E-mail:

Funding source: U.S. Army Medical Research and Material Command Fort Detrick, Maryland 21702-5012 http://dx.doi.org/10.13039/100016156

Award Identifier / Grant number: W81XWH-19-1-0786 (Fortner)

Acknowledgments

We are grateful to all the MARIE study participants for their contribution and the interviewers who collected the data. We thank Muhabbet Celik for sample preparation and sample coordination, and the biocrates service lab team for their expert advice in interpreting the oxysterol data. We express gratitude to Dieter Flesch-Janys for his invaluable contributions to the MARIE projects as former PI of the Hamburg study region. The MARIE study was funded by the German Cancer Aid (Deutsche Krebshilfe e.V.; Grant numbers 70-2892-BR I, 108419 and 108253, 110826 and 110828), the German Cancer Research Center (DKFZ), and the Hamburg Cancer Society.

  1. Research funding: This work was supported by the U.S. Army Medical Research and Material Command Fort Detrick, Maryland 21702-5012 under Award No. W81XWH-19-1-0786 (Fortner). The funding organization played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The research related to human use has complied with all the relevant national regulations, institutional policies, and in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ Institutional Review Board or equivalent committee (Ethics Committees of the University of Heidelberg, S-685/2019).

  6. Data availability: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2022-0705).


Received: 2022-04-01
Accepted: 2022-10-25
Published Online: 2022-11-08
Published in Print: 2023-01-27

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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