Association between lifestyle, dietary, reproductive, and anthropometric factors and circulating 27-hydroxycholesterol in EPIC-Heidelberg



Given that 27-hydroxycholesterol (27HC) is the first identified endogenous selective estrogen receptor modulator, the aim of this study was to investigate the extent to which dietary or lifestyle factors impact circulating 27HC concentrations in a large-scale setting.


This cross-sectional analysis included 1,036 women aged 35–65 years who served as controls in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg breast cancer case–control study. Circulating 27HC was quantified in serum using liquid chromatography/tandem mass spectrometry. Generalized linear models were used to investigate the association between 27HC concentrations and dietary habits, and lifestyle, reproductive, and anthropometric factors.


Higher concentrations of 27HC were observed among postmenopausal relative to premenopausal women (geometric mean 200.5 vs. 188.4 nM, p = 0.03), whereas women reporting ever full-term pregnancy had lower concentrations of 27HC relative to never (191.4 vs. 198.6; p = 0.03). Significant trends were observed showing higher concentrations with relatively high levels of physical activity (ptrend = 0.03) and alcohol consumption (ptrend = 0.01), and women currently smoking at blood collection (ptrend < 0.01). Of the investigated dietary factors, starch (ptrend < 0.01) and thiamine (ptrend < 0.01) intakes were inversely associated with 27HC. Circulating lipid concentrations were positively associated with 27HC concentrations (all ptrend < 0.01). No significant associations were found between 27HC and factors including age at blood collection, body mass index, or use of hormone therapy or cholesterol-lowering medications.


27HC is of increasing interest for multiple chronic disease pathways. Despite significant associations found between circulating 27HC and dietary habits, reproductive factors, and modifiable lifestyle factors, circulating cholesterol, mostly low-density lipoprotein cholesterol, accounted for the majority of the variability in circulating 27HC.

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This study was supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Breast Cancer Research Program under Award No. W81XWH-15–1-0035 (Fortner). Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. EPIC-Heidelberg was funded by the German Federal Ministry of Education and Research (BMBF) Grant 01ER0809 (Kaaks).

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Correspondence to Charlotte Le Cornet.

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The EPIC study protocol was approved by the Ethical Committees of the International Agency for Research on Cancer (IARC) and the Ethics Committee of the Medical Faculty in Heidelberg. The study has been performed in accordance with the principles expressed in the Helsinki Declaration of 1996, Conventions of the Council of Europe on Human Rights and Biomedicine.

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Le Cornet, C., Johnson, T.S., Lu, D. et al. Association between lifestyle, dietary, reproductive, and anthropometric factors and circulating 27-hydroxycholesterol in EPIC-Heidelberg. Cancer Causes Control 31, 181–192 (2020).

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  • 27-Hydroxycholesterol
  • SERM
  • Cross-sectional study
  • Woman
  • Dietary intakes (diet, food, and nutrition)
  • Epidemiologic factors