Abstract
BackgroundGermline 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.MethodsThe 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.ResultsAt 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.ConclusionOur results give first indications for lifestyle-related modification particularly of pro-NT in gBMC.
Highlights
Background GermlineBRCA1/2 mutation carriers face increased cancer risks that are modulated via non-genetic lifestyle factors whose underlying molecular mechanisms are unknown
The identification of lifestyle-related biomarkers for molecular mechanisms that are involved in tumorigenesis in gBRCA1/2 mutation carriers is important and certain promising biomarkers were measured in the LIBRE-1 trial
We focused on the LIBRE-1-total participants
Summary
Background GermlineBRCA1/2 mutation carriers (gBMC) face increased cancer risks that are modulated via non-genetic lifestyle factors whose underlying molecular mechanisms are unknown. Conclusion Our results give first indications for lifestyle-related modification of pro-NT in gBMC Lifestyle factors such as physical inactivity, obesity and hypercaloric nutrition have been shown to substantially impact breast cancer (BC) risk [1,2,3,4,5,6,7]. Amongst other reasons this increase might be attributed to an alteration of the social and lifestyle environment [8, 11] In light of this the LIBRE-1 trial, a prospective lifestyleintervention randomized controlled trial, was initiated to investigate whether a structured 1-year intervention program ameliorates cardiopulmonary fitness, body mass index (BMI) and the nutritional pattern in female gBRCA1/2 mutation carriers [12,13,14]. Two of these, which are the focus of this work: neurotensin (NT) and enkephalin (ENK) have been identified as markers linking cardiovascular, cardiometabolic and cancer risk
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