Browsing by Author "Brenner, Darren R"

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    Effects of physical activity on colorectal cancer risk among family history and body mass index subgroups: a systematic review and meta-analysis
    (2018-01-11) Shaw, Eileen; Farris, Megan S; Stone, Chelsea R; Derksen, Jeroen W G; Johnson, Rhys; Hilsden, Robert J; Friedenreich, Christine M; Brenner, Darren R
    Abstract Background Physical activity is consistently associated with a reduced risk of colorectal cancer in epidemiologic studies. This association among higher risk subgroups, such as those with a first-degree family history of colorectal cancer or high body mass index remains unclear. Methods We searched MEDLINE for studies examining physical activity and colorectal cancer risk among higher risk subgroups through July 11, 2017. Fifteen and three studies were eligible for inclusion for body mass index and first-degree family history of colorectal cancer subgroups, respectively. Estimates of the highest to lowest comparison of physical activity for each subgroup of risk were pooled using random-effects models. Results The pooled associations of physical activity and colorectal cancer risk for those without and with a first-degree family history of colorectal cancer were 0.56 (95% confidence interval (CI) = 0.39–0.80) and 0.72 (95% CI = 0.39–1.32), respectively (pheterogeneity = 0.586). The pooled associations of physical activity and colorectal cancer risk for the low and high body mass index groups were 0.74 (95% CI = 0.66–0.83) and 0.65 (95% CI = 0.53–0.79), respectively (pheterogeneity = 0.389). Conclusions Overall, a stronger relative risk of physical activity on colorectal cancer risk was observed in the higher body mass index group, although the difference was not statistically significant, suggesting an added benefit of physical activity as a cancer prevention strategy in population groups with strong risk factors for colorectal cancer. Additional research among these subgroups is warranted.
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    Measures of excess body weight and anthropometry among adult Albertans: cross-sectional results from Alberta’s tomorrow project cohort
    (2017-11-25) Brenner, Darren R; Poirier, Abbey E; Haig, Tiffany R; Akawung, Alianu; Friedenreich, Christine M; Robson, Paula J
    Abstract Background Excess body weight during adulthood has been consistently associated with all-cause mortality, cardiovascular disease, and cancer at multiple sites among other chronic diseases. We describe the prevalence of excess body weight and abdominal obesity reported by participants enrolled in Alberta’s Tomorrow Project (ATP). Methods ATP is a geographically-based cohort study conducted among adults aged 35–69 years from across the province of Alberta. Participants completed anthropometric measures and health and lifestyle questionnaires at enrolment. Overweight and obese were categorized as a body mass index (BMI) of 25.0–29.9 kg/m2 and ≥30 kg/m2, respectively. Abdominal obesity was categorized using cut-offs of waist circumference of >94 cm for men and >80 cm for women and waist-tp-hip ratio cut-offs of >0.90 for men and >0.85 for women. Results BMI and hip and waist circumference data were obtained from 12,062 men and 18,853 women enrolled between 2001 and 2009. Overall, 76.8% of men and 59.5% of women reported a BMI ≥25 kg/m2. The proportions of overweight and obese were significantly higher in older age groups (p < 0.001). In addition, the proportion of participants reporting being overweight and obese was higher among lower education (p < 0.001) and lower income groups (p < 0.001). Overall, approximately two thirds of men and women in ATP cohort reported abdominal obesity. Overweight, obesity and abdominal obesity were all associated with a history of several cardiometabolic chronic conditions including hypertension, heart attack, angina, high cholesterol, stroke and diabetes. Conclusion A large majority of ATP participants were overweight and carried excess abdominal fat. Strategies to improve energy balance among Albertans are encouraged and may have a notable impact on future chronic disease burden.
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    Mutational landscape differences between young-onset and older-onset breast cancer patients
    (2020-03-12) Mealey, Nicole E; O’Sullivan, Dylan E; Pader, Joy; Ruan, Yibing; Wang, Edwin; Quan, May L; Brenner, Darren R
    Abstract Background The incidence of breast cancer among young women (aged ≤40 years) has increased in North America and Europe. Fewer than 10% of cases among young women are attributable to inherited BRCA1 or BRCA2 mutations, suggesting an important role for somatic mutations. This study investigated genomic differences between young- and older-onset breast tumours. Methods In this study we characterized the mutational landscape of 89 young-onset breast tumours (≤40 years) and examined differences with 949 older-onset tumours (> 40 years) using data from The Cancer Genome Atlas. We examined mutated genes, mutational load, and types of mutations. We used complementary R packages “deconstructSigs” and “SomaticSignatures” to extract mutational signatures. A recursively partitioned mixture model was used to identify whether combinations of mutational signatures were related to age of onset. Results Older patients had a higher proportion of mutations in PIK3CA, CDH1, and MAP3K1 genes, while young-onset patients had a higher proportion of mutations in GATA3 and CTNNB1. Mutational load was lower for young-onset tumours, and a higher proportion of these mutations were C > A mutations, but a lower proportion were C > T mutations compared to older-onset tumours. The most common mutational signatures identified in both age groups were signatures 1 and 3 from the COSMIC database. Signatures resembling COSMIC signatures 2 and 13 were observed among both age groups. We identified a class of tumours with a unique combination of signatures that may be associated with young age of onset. Conclusions The results of this exploratory study provide some evidence that the mutational landscape and mutational signatures among young-onset breast cancer are different from those of older-onset patients. The characterization of young-onset tumours could provide clues to their etiology which may inform future prevention. Further studies are required to confirm our findings.
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    Physical activity does not alter prolactin levels in post-menopausal women: results from a dose-response randomized controlled trial
    (2017-07-13) Brenner, Darren R; Ruan, Yibing; Morielli, Andria R; Courneya, Kerry S; Friedenreich, Christine M
    Abstract Background Increased circulating levels of prolactin have been associated with increased risk of both in situ and invasive breast cancer. We investigated whether or not physical activity had a dose–response effect in lowering plasma levels of prolactin in postmenopausal women. Methods Four hundred previously inactive but healthy postmenopausal women aged 50–74 years of age were randomized to 150 or 300 min per week of aerobic physical activity in a year-long intervention. Prolactin was measured from fasting samples with a custom-plex multiplex assay. Results A high compared to moderate volume of physical activity did not reduce plasma prolactin levels in intention-to-treat (Treatment Effect Ratio (TER) 1.00, 95% Confidence Interval (CI) 0.95 – 1.06) or per-protocol analyses (TER 1.02, 95% CI 0.93 – 1.13). Conclusions It is unlikely that changes in prolactin levels mediate the reduced risk of breast cancer development in post-menopausal women associated with increased levels of physical activity. Trial registration clinicaltrials.gov identifier: NCT01435005 .
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    The impact of exercise on growth factors (VEGF and FGF2): results from a 12-month randomized intervention trial
    (2019-06-24) Brenner, Darren R; Ruan, Yibing; Adams, Scott C; Courneya, Kerry S; Friedenreich, Christine M
    Abstract Background Vascular endothelial growth factor (VEGF) and Fibroblast growth factor-2 (FGF2) are angiogenic cytokines in normal tissues and tumors. Evidence suggests that increased growth factor expression in adipose tissue leads to improved vascularity and decreased hypoxia, fibrosis, and inflammation, which may, in turn, reduce post-menopausal breast cancer risk. Objective We investigated whether or not exercise had dose-response effects on levels of plasma VEGF and FGF2 in postmenopausal women. Methods Four hundred previously inactive but healthy postmenopausal women aged 50–74 years of age were randomized to 150 or 300 min per week of aerobic exercise in a year-long exercise intervention. VEGF and FGF2 were measured from fasting serum samples with a custom-plex multiplex assay. Results A high compared to moderate volume of aerobic exercise did not cause chronic changes in plasma VEGF or FGF2 levels in intention-to-treat or per-protocol analyses. Conclusions We did not detect differences in growth factor levels related to increasing doses of exercise. It is unlikely that changes in VEGF and FGF2 levels mediate the reduction in risk of post-menopausal breast cancer development in associated with increased levels of exercise. Trial registration Clinicaltrials.gov identifier: NCT01435005.
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    Trajectories of physical activity, from young adulthood to older adulthood, and pancreatic cancer risk; a population-based case-control study in Ontario, Canada
    (2020-02-21) Sandhu, Jaspreet; De Rubeis, Vanessa; Cotterchio, Michelle; Smith, Brendan T; Griffith, Lauren E; Brenner, Darren R; Borgida, Ayelet; Gallinger, Steven; Cleary, Sean; Anderson, Laura N
    Abstract Background There is inconsistent evidence on the association between physical activity and pancreatic cancer risk and few studies have investigated early life or life-course physical activity. The objective of this study was to evaluate the association between trajectories of physical activity across the life-course and pancreatic cancer risk. Methods A population-based case-control study was conducted (2011–2013) using cases (n = 315) from the Ontario Pancreas Cancer Study and controls (n = 1254) from the Ontario Cancer Risk Factor Study. Self-reported recall of moderate and vigorous physical activity was measured at three time points: young adulthood (20s–30s), mid-adulthood (40s–50s) and older-adulthood (1 year prior to questionnaire completion). Physical activity trajectories were identified using latent class analysis. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from multivariable logistic regression adjusted for covariates: age, sex, race, alcohol, smoking, vegetable, fruit and meat consumption, and family history of pancreatic cancer. Results Six life-course physical activity trajectories were identified: inactive at all ages (41.2%), low activity at all ages (31.9%), increasingly active (3.6%), high activity in young adulthood with substantial decrease (13.0%), high activity in young adulthood with slight decrease (5.0%), and persistent high activity (5.3%). Compared to the inactive at all ages trajectory, the associations between each trajectory and pancreatic cancer after confounder adjustment were: low activity at all ages (OR: 1.11; 95% CI: 0.75, 1.66), increasingly active (OR: 1.11; 95% CI: 0.56, 2.21), high activity in young adulthood with substantial decrease in older adulthood (OR: 0.76; 95% CI: 0.47, 1.23), high activity in young adulthood with slight decrease in older adulthood (OR: 0.98; 95% CI: 0.62, 1.53), and persistently high activity (OR: 1.50; 95% CI: 0.86, 2.62). When time periods were evaluated separately, the OR for the association between high moderate activity in the 20s–30s and pancreatic cancer was 0.89 (95% CI: 0.64, 1.25) and some sex differences were observed. Conclusion Distinct life-course physical activity trajectories were identified, but there was no evidence that any of the trajectories were associated with pancreatic cancer. Future studies with larger sample sizes are needed to understand the associations between physical activity trajectories over the life-course and pancreatic cancer risk.