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.

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.

Smoking and physical inactivity increase cancer prevalence in BRCA-1 and BRCA-2 mutation carriers: results from a retrospective observational analysis.

BACKGROUND: The aim of this analysis in a pilot study population was to investigate whether we can verify seemingly harmful lifestyle factors such as nicotine and alcohol indulgence, obesity, and physical inactivity, as well as a low socioeconomic status for increased cancer prevalence in a cohort of BRCA 1 and 2 mutation carriers. METHODS: The analysis data are derived from 68 participants of the lifestyle intervention study LIBRE-1, a randomized, prospective trial that aimed to test the feasibility of a lifestyle modification in BRCA 1 and 2 mutation carriers. At study entry, factors such as medical history, lifestyle behavior, and socioeconomic status were retrospectively documented by interview and the current BMI was determined by clinical examination. The baseline measurements were compared within the cohort, and presented alongside reference values for the German population. RESULTS: Study participants indicating a higher physical activity during their adolescence showed a significantly lower cancer prevalence (p = 0.019). A significant difference in cancer occurrence was observed in those who smoked prior to the disease, and those who did not smoke (p < 0.001). Diseased mutation carriers tended to have a lower BMI compared to non-diseased mutation carriers (p = 0.079), whereas non-diseased revealed a significantly higher physical activity level than diseased mutation carriers (p = 0.046). DISCUSSION: The present data in this small cohort of 68 mutation carriers suggest that smoking and low physical activity during adolescence are risk factors for developing breast cancer in women with BRCA1 or BRCA2 mutation. Further data of the ongoing LIBRE 2 study are necessary to confirm these findings in a larger cohort of 600 mutation carriers.