Uninterrupted Sedentary Behavior Downregulates BRCA1 Gene Expression

Abstract

BRCA1 mutation carriers face a high lifetime risk of developing breast cancer. Physical activity induces broad transcriptional changes, and multiple studies have documented its beneficial effects across cancers. Because haploinsufficiency predisposes to breast cancer in these women, factors that increase BRCA1 levels may mitigate the effect of the mutation. Whether physical activity modulates BRCA1 expression and whether lifestyle factors could benefit women with a mutation remain unclear. The objective of this study was to systematically evaluate whether physical activity or sedentary behavior affects BRCA1 mRNA expression. Activity levels were assessed in 50 female participants (14 BRCA1 mutation carriers and 36 noncarriers) using the GT3X Actigraph accelerometer, and BRCA1 mRNA expression was quantified from peripheral blood lymphocytes using the Nanostring nCounter Analysis System. There was a significant negative correlation between the longest sedentary bout and BRCA1 mRNA expression (r ¼ -0.32; P ¼ 0.02). Women below the median for the longest sedentary bout had significantly higher BRCA1 mRNA levels compared with women above the median (161 vs. 132 counts; P ¼ 0.04; one-sided Mann-Whitney U test). There was no significant relationship between mean metabolic equivalents of task rate or mean sedentary time and BRCA1 mRNA expression (Spearman correlation P ! 0.75; P ! 0.14; Mann-Whitney U test). These findings suggest that prolonged periods of sedentary behavior are associated with significantly lower BRCA1 mRNA expression. Whether this translates into a potentially more harmful effect in BRCA1 mutation carriers warrants further investigation. Cancer Prev Res; 9(1); 83-88. Ó2015 AACR.

Estrogen Receptor 1 Inhibition of Wnt/β-Catenin Signaling Contributes to Sex Differences in Hepatocarcinogenesis

“…In terms of processes, ESR1 significantly impacted transcription regulation, histone methylation, DNA repair, cell cycle and senescence. The effect of ESR1 on these processes is compatible with the literature on the impact of ESR1 in other cancers (52)(53)(54)(55)(56)(57)(58)(59)(60), with impact on transcriptional regulation (61), cell cycle, and tumor suppression (62). Interestingly, ER-a antagonist did not produce the opposite effect, but rather resulted in tumor burden similar to the control conditions.…”

Modifiable Lifestyle Factors: Opportunities for (Hereditary) Breast Cancer Prevention - a Narrative Review

“…Additionally, we observed a significantly higher cancer prevalence in smokers compared to non-smokers (p < 0.001) [49]. Pettapiece-Phillips et al [50] showed that uninterrupted sedentary behavior was associated with decreased BRCA1 mRNA expression (p = 0.02). Whether this finding translates into a potentially harmful effect with regard to BRCA-associated cancer risk is under active study.…”

Association between average daily television viewing time and the incidence of ovarian cancer: findings from the Japan Collaborative Cohort Study

“…Multivariate hazard ratios (HR) and confidence intervals (CI) for the incidence of ovarian cancer were calculated using an inverse probability weighted (IPW) [19,20] competing risk model [21] in which we treated incidence of cancer other than ovarian cancer and death as a competing events [22]. To develop the generalized propensity score, we conducted a multinomial logistic regression analysis using variables for all demographic information [23], including age (a continuous variable), body mass index (BMI; <18.5, 18.5-24.9, or ≥25.0 kg/m 2 , or missing), educational level (school up to age 15, 15-18, or ≥19 years, or missing), smoking status (never, former, or current smoker, or missing), alcohol drinking status (never, former, or current alcohol drinker, or missing), average daily sleeping time (<6.5, 6.5-8.4, or ≥8.5 hours/day, or missing), average daily walking time (<1, ≥1 hours/day, or missing), age at menarche (<13, 13-15, or ≥16 years, or missing), age at menopause (<44, 44-48, 49-52, or ≥52 years, or having periods/missing), parity (none, 1-2, ≥3 times, or missing), use of hormone therapy ever (never, user, or missing), family history of breast, ovarian, or prostate cancer (yes or no/missing) [24]. To assess the covariate balance, we showed the propensity score overlap using kernel density plots.…”