title: 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 (ρ = -0.32; P = 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 = 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.
authors.affiliation: Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada. Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Rachael
authors.initials: R
authors.lastname: Pettapiece-Phillips
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, IBM Life Sciences Discovery Centre, Toronto, Ontario, Canada.
authors.forename: Max
authors.initials: M
authors.lastname: Kotlyar
authors.affiliation: Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada.
authors.forename: Rania
authors.initials: R
authors.lastname: Chehade
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, IBM Life Sciences Discovery Centre, Toronto, Ontario, Canada. Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Salmena
authors.affiliation: Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada. Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada. Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
authors.affiliation: Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada. Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Akbari
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, IBM Life Sciences Discovery Centre, Toronto, Ontario, Canada. Department of Medical Biophysics and Department of Computer Science, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Igor
authors.initials: I
authors.lastname: Jurisica
authors.affiliation: Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada. Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada. Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada. joanne.kotsopoulos@wchospital.ca.
authors.forename: Joanne
authors.initials: J
authors.lastname: Kotsopoulos
mesh_terms: D061725:Accelerometry; D056044:Actigraphy; D000293:Adolescent; D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006579:Heterozygote; D006801:Humans; D008019:Life Style; D008214:Lymphocytes / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D057185:Sedentary Behavior; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D012333:RNA, Messenger