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Epidemiology

Lipoprotein and metabolite associations to breast cancer risk in the HUNT2 study

Abstract

Background

The aim of this study was to gain an increased understanding of the aetiology of breast cancer, by investigating possible associations between serum lipoprotein subfractions and metabolites and the long-term risk of developing the disease.

Methods

From a cohort of 65,200 participants within the Trøndelag Health Study (HUNT study), we identified all women who developed breast cancer within a 22-year follow-up period. Using nuclear magnetic resonance (NMR) spectroscopy, 28 metabolites and 89 lipoprotein subfractions were quantified from prediagnostic serum samples of future breast cancer patients and matching controls (n = 1199 case–control pairs).

Results

Among premenopausal women (554 cases) 14 lipoprotein subfractions were associated with long-term breast cancer risk. In specific, different subfractions of VLDL particles (in particular VLDL-2, VLDL-3 and VLDL-4) were inversely associated with breast cancer. In addition, inverse associations were detected for total serum triglyceride levels and HDL-4 triglycerides. No significant association was found in postmenopausal women.

Conclusions

We identified several associations between lipoprotein subfractions and long-term risk of breast cancer in premenopausal women. Inverse associations between several VLDL subfractions and breast cancer risk were found, revealing an altered metabolism in the endogenous lipid pathway many years prior to a breast cancer diagnosis.

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Fig. 1: Scores and loading plots from PLS-DA for discrimination of pre- or postmenopausal women from their lipid profiles (analysis has been restricted to the controls).
Fig. 2: Odds ratios and 95% confidence intervals per 1 SD increase for lipoprotein subfractions associated with long-term breast cancer risk in premenopausal women participating in the HUNT2 study.
Fig. 3: Lipoprotein metabolism.

Data availability

The Trøndelag Health Study (HUNT) has invited persons aged 13–100 years to four surveys between 1984 and 2019. Comprehensive data from more than 140,000 persons having participated at least once and biological material from 78,000 persons are collected. The data are stored in HUNT databank and biological material in HUNT biobank. HUNT Research Centre has permission from the Norwegian Data Inspectorate to store and handle these data. The key identification in the database is the personal identification number given to all Norwegians at birth or immigration, whilst de-identified data are sent to researchers upon approval of a research protocol by the Regional Ethical Committee and HUNT Research Centre. To protect participants’ privacy, HUNT Research Centre aims to limit the storage of data outside HUNT databank, and cannot deposit data in open repositories. HUNT databank has precise information on all data exported to different projects and are able to reproduce these on request. There are no restrictions regarding data export given approval of applications to HUNT Research Centre. For more information, see http://www.ntnu.edu/hunt/data.

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Acknowledgements

The Trøndelag Health Study (HUNT) is a collaboration between HUNT Research Centre (Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology NTNU), Trøndelag County Council, Central Norway Regional Health Authority, and the Norwegian Institute of Public Health. The NMR analyses were performed at the MR Core Facility, Norwegian University of Science and Technology (NTNU), funded by the Faculty of Medicine at NTNU and Central Norway Regional Health Authority, and at Bruker BioSpin GmbH, Germany. HS, FF, CC and MS are employed at Bruker BioSpin. Bruker BioSpin has funded the release of the samples from the HUNT biobank.

Funding

This work has been supported by the Norwegian Financial Mechanism (2014-2021, JD, TFB, Project 2019/34/H/NZ7/00503) the Norwegian Cancer Society (GFG, 6834362 and 202021); Stiftelsen DAM (FW, 2020/FO298770); The K.G. Jebsen Foundation, the Liaison Committee for education, research and innovation in Central Norway (FW, 2020/3806-4), and the Joint Research Committee between St. Olavs hospital and the Faculty of Medicine and Health Sciences, NTNU (GFG, 28328 and TFB, 28346).

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Authors

Contributions

Conceptualisation: JD, TFB and GFG. Data curation: JD, TFB and GFG. Formal analysis: JD, TA, TFB and GFG. Funding acquisition: TFB and GFG. Investigation: JD, HS, TA, FW, FF, CC and GFG. Methodology: JD, HS, TA, MS, TFB and GFG. Software: HS and MS. Supervision: TFB and GFG. Visualisation: JD. Writing—original draft: JD. Writing—review and editing: JD, HS, TA, FW, FF, CC, MS, TFB and GFG.

Corresponding authors

Correspondence to Julia Debik or Guro F. Giskeødegård.

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The authors declare no competing interests.

Ethics approval and consent to participate

All participants have completed a written informed consent form, and the study was approved by the Ethics Committee of Central Norway (REK numbers #1995/8395 and #2017/2231).

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Debik, J., Schäfer, H., Andreassen, T. et al. Lipoprotein and metabolite associations to breast cancer risk in the HUNT2 study. Br J Cancer (2022). https://doi.org/10.1038/s41416-022-01924-1

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