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Open Access 01-04-2021 | Breast Cancer | Clinical trial

Precursor fractions of neurotensin and enkephalin might point to molecular mechanisms of cancer risk modulation during a lifestyle-intervention in germline BRCA1/2 gene mutation carriers

Authors: Sabine Grill, Maryam Yahiaoui-Doktor, Maryam Basrai, Joachim Struck, Janin Schulte, Anika Berling-Ernst, Christoph Engel, Mirjam Ullrich, Jacqueline Lammert, Stephan C. Bischoff, Thorsten Schmidt, Uwe Niederberger, Dimitrios Chronas, Kerstin Rhiem, Rita Schmutzler, Martin Halle, Marion Kiechle

Published in: Breast Cancer Research and Treatment | Issue 3/2021

Abstract

Background

Germline BRCA1/2 mutation carriers (gBMC) face increased cancer risks that are modulated via non-genetic lifestyle factors whose underlying molecular mechanisms are unknown. The peptides Neurotensin (NT) and Enkephalin (ENK)—involved in tumorigenesis and obesity-related diseases—are of interest. We wanted to know whether these biomarkers differ between gBMC and women from the general population and what effect a 1-year lifestyle-intervention has in gBMC.

Methods

The stable precursor fragments pro-NT and pro-ENK were measured at study entry (SE), after 3 and 12 months for 68 women from LIBRE-1 (a controlled lifestyle-intervention feasibility trial for gBMC involving structured endurance training and the Mediterranean Diet). The SE values were compared with a cohort of the general population including female subjects with and without previous cancer disease, non-suggestive for hereditary breast and ovarian cancer (OMA-reference). For LIBRE-1, we analysed the association between the intervention-related change in the two biomarkers and certain lifestyle factors.

Results

At SE, gBMC had a higher median pro-NT than OMA-reference (in the subgroups with previous cancer 117 vs. 91 pmol/L, p = 0.002). Non-diseased gBMC had lower median pro-ENK levels when compared to the non-diseased reference group. VO2peak and pro-NT 1-year change in LIBRE-1 were inversely correlated (r = − 0.435; CI − 0.653 to − 0.151; p = 0.004). Pro-ENK correlated positively with VO2peak at SE (r = 0.323; CI 0.061–0.544; p = 0.017). Regression analyses showed an inverse association of 1-year changes for pro-NT and Omega-6/Omega-3 (Estimate: − 37.9, p = 0.097/0.080) in multivariate analysis.

Conclusion

Our results give first indications for lifestyle-related modification particularly of pro-NT in gBMC.

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Title: Precursor fractions of neurotensin and enkephalin might point to molecular mechanisms of cancer risk modulation during a lifestyle-intervention in germline BRCA1/2 gene mutation carriers
Authors: Sabine Grill
Maryam Yahiaoui-Doktor
Maryam Basrai
Joachim Struck
Janin Schulte
Anika Berling-Ernst
Christoph Engel
Mirjam Ullrich
Jacqueline Lammert
Stephan C. Bischoff
Thorsten Schmidt
Uwe Niederberger
Dimitrios Chronas
Kerstin Rhiem
Rita Schmutzler
Martin Halle
Marion Kiechle
Publication date: 01-04-2021
Publisher: Springer US
Keywords: Breast Cancer
Nutrition
Ovarian Cancer
Ovarian Cancer
Breast Cancer
Published in: Breast Cancer Research and Treatment / Issue 3/2021
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-020-06070-x

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Abstract

Background

Methods

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