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.


Journal

Breast cancer research and treatment
ISSN: 1573-7217
Titre abrégé: Breast Cancer Res Treat
Pays: Netherlands
ID NLM: 8111104

Informations de publication

Date de publication:
Apr 2021
Historique:
received: 10 11 2020
accepted: 23 12 2020
pubmed: 6 2 2021
medline: 24 6 2021
entrez: 5 2 2021
Statut: ppublish

Résumé

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

Sections du résumé

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

Identifiants

pubmed: 33543354
doi: 10.1007/s10549-020-06070-x
pii: 10.1007/s10549-020-06070-x
pmc: PMC8019429
doi:

Substances chimiques

BRCA1 Protein 0
BRCA1 protein, human 0
Enkephalins 0
Neurotensin 39379-15-2

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

741-752

Subventions

Organisme : Deutsche Krebshilfe
ID : Grant no. 110013

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Auteurs

Sabine Grill (S)

Department of Gynecology and Center for Hereditary Breast and Ovarian Cancer, Klinikum Rechts Der Isar, Technical University Munich (TUM), Munich, Germany. Sabine.Grill@tum.de.

Maryam Yahiaoui-Doktor (M)

Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany.

Maryam Basrai (M)

Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.

Joachim Struck (J)

SphingoTec GmbH, Hennigsdorf, Germany.

Janin Schulte (J)

SphingoTec GmbH, Hennigsdorf, Germany.

Anika Berling-Ernst (A)

Department of Prevention, Rehabilitation and Sports Medicine, Faculty of Medicine, University Hospital Rechts Der Isar, Technical University of Munich (TUM), Munich, Germany.

Christoph Engel (C)

Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany.

Mirjam Ullrich (M)

Department of Gynecology and Center for Hereditary Breast and Ovarian Cancer, Klinikum Rechts Der Isar, Technical University Munich (TUM), Munich, Germany.

Jacqueline Lammert (J)

Department of Gynecology and Center for Hereditary Breast and Ovarian Cancer, Klinikum Rechts Der Isar, Technical University Munich (TUM), Munich, Germany.

Stephan C Bischoff (SC)

Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.

Thorsten Schmidt (T)

Comprehensive Cancer Center, University Hospital Schleswig-Holstein, Kiel, Germany.

Uwe Niederberger (U)

Institute for Medical Psychology and Medical Sociology, University Hospital Schleswig-Holstein, Kiel, Germany.

Dimitrios Chronas (D)

Department of Gynecology and Center for Hereditary Breast and Ovarian Cancer, Klinikum Rechts Der Isar, Technical University Munich (TUM), Munich, Germany.

Kerstin Rhiem (K)

Center for Hereditary Breast and Ovarian Cancer, University Hospital Cologne, Cologne, Germany.

Rita Schmutzler (R)

Center for Hereditary Breast and Ovarian Cancer, University Hospital Cologne, Cologne, Germany.

Martin Halle (M)

Department of Prevention, Rehabilitation and Sports Medicine, Faculty of Medicine, University Hospital Rechts Der Isar, Technical University of Munich (TUM), Munich, Germany.

Marion Kiechle (M)

Department of Gynecology and Center for Hereditary Breast and Ovarian Cancer, Klinikum Rechts Der Isar, Technical University Munich (TUM), Munich, Germany.

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