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

• DOI: 10.1007/s10549-020-06070-x
• Publication Date: 2021-02-04T18:22:35Z
• Authors: Sabine Grill; Maryam Yahiaoui-D...; 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
• Keywords: 0301 basic medicine; BRCA1 Protein; Female [MeSH] ; Nutrition ; Mutation [MeSH] ; BRCA1 Protein/genetics [MeSH] ; Humans [MeSH] ; Clinical Trial ; Breast Neoplasms/genetics [MeSH] ; Breast cancer ; Life Style [MeSH] ; Breast Neoplasms/epidemiology [MeSH] ; Neurotensin/genetics [MeSH] ; Enkephalins/genetics [MeSH] ; Germ-Line Mutation [MeSH] ; Physical activity ; Cardiopulmonary fitness ; Lifestyle intervention ; Germ Cells [MeSH]; Breast Neoplasms; Enkephalins; Clinical Trial; ddc:; 3. Good health; 03 medical and health sciences; Germ Cells; Mutation; Humans; Female; Life Style; Germ-Line Mutation; Neurotensin

Abstract Background Germline BRCA1/2 mutation carriers (gBMC) face increased cancer risks that are modulated via non-genetic lifestyle factors whose underlying molecular mechanisms unknown. The peptides Neurotensin (NT) and Enkephalin (ENK)—involved in tumorigenesis obesity-related diseases—are of interest. We wanted to know whether these biomarkers differ between gBMC women from the general population what effect a 1-year lifestyle-intervention has gBMC. Methods stable precursor fragments pro-NT pro-ENK were measured at study entry (SE), after 3 12 months for 68 LIBRE-1 (a controlled feasibility trial involving structured endurance training Mediterranean Diet). SE values compared with cohort including female subjects without previous disease, non-suggestive hereditary breast ovarian (OMA-reference). For LIBRE-1, we analysed association intervention-related change two certain factors. Results At SE, had higher median than OMA-reference (in subgroups 117 vs. 91 pmol/L, p = 0.002). Non-diseased lower levels when non-diseased reference group. VO2peak inversely correlated ( r − 0.435; CI 0.653 0.151; 0.004). Pro-ENK positively 0.323; 0.061–0.544; 0.017). Regression analyses showed an inverse changes Omega-6/Omega-3 (Estimate: 37.9, 0.097/0.080) multivariate analysis. Conclusion Our results give first indications lifestyle-related modification particularly