Publications by authors named "Christine M Friedenreich"

257 Publications

Estimates of future cancer mortality attributable to modifiable risk factors in Canada.

Can J Public Health 2021 May 25. Epub 2021 May 25.

Department of Cancer Epidemiology and Prevention Research, Cancer Care Alberta, Alberta Health Services, Holy Cross Centre, Room 513C, Box ACB, 2210-2nd St. SW, Calgary, AB, T2S 3C3, Canada.

Objectives: Modifiable lifestyle, environmental, and infectious risk factors associated with cancer impact both cancer incidence and mortality at the population level. Most studies estimating this burden focus on cancer incidence. However, because these risk factors are associated with cancers of disparate mortality rates, the burden associated with cancer incidence could differ from cancer mortality. Therefore, estimating the cancer mortality attributable to these risk factors provides additional insight into cancer prevention. Here, we estimated future cancer deaths and the number of avoidable deaths in Canada due to modifiable risk factors.

Methods: The projected cancer mortality data came from OncoSim, a web-based microsimulation tool. These data were applied to the methodological framework that we previously used to estimate the population attributable risks and the potential impact fractions of modifiable risk factors on Canadian cancer incidence.

Results: We estimated that most cancer deaths will be attributed to tobacco smoking with an average of 27,900 deaths annually from 2024 to 2047. If Canada's current trends in excess body weight continue, cancer deaths attributable to excess body weight would double from 2786 deaths in 2024 to 5604 deaths in 2047, becoming the second leading modifiable cause of cancer death. Applying targets to reduce these risk factors, up to 34,600 cancer deaths could be prevented from 2024 to 2047.

Conclusion: Our simulated results complement our previous findings on the cancer incidence burden since decreasing the overall burden of cancer will be accelerated through a combination of decreasing cancer incidence and improving survival outcomes through improved treatments.
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http://dx.doi.org/10.17269/s41997-020-00455-7DOI Listing
May 2021

Estimating the future cancer management costs attributable to modifiable risk factors in Canada.

Can J Public Health 2021 May 25. Epub 2021 May 25.

Department of Cancer Epidemiology and Prevention Research, CancerControl Alberta, Alberta Health Services, Calgary, Alberta, T2S 3C3, Canada.

Objectives: An estimated 33-37% of incident cancers in Canada are attributable to modifiable risk factors. Interventions targeting these risk factors would minimize the substantial health and economic burdens Canadians face due to cancer. We estimate the future health and economic burden of cancer in Canada by incorporating data from the Canadian Population Attributable Risk of Cancer (ComPARe) study into OncoSim, a web-based microsimulation tool.

Methods: Using the integrated OncoSim population attributable risk and population impact measures, we evaluated risk factor-targeted intervention scenarios implemented in 2020, assuming the targeted risk factor prevalence reduction would be achieved by 2032 with a 12-year latency period.

Results: We estimate that smoking will be the largest contributor to cancer-related costs, with a cost of CAD $44.4 billion between 2032 and 2044. An estimated CAD $3.3 billion of the cost could be avoided with a 30% reduction in smoking prevalence by 2022. Following smoking, the next highest cancer management costs are associated with inadequate physical activity and excess body weight, accounting for CAD $10.7 billion ($2.7 billion avoidable) and CAD $9.8 billion ($3.2 billion avoidable), respectively. Avoidable costs for other risk factors range from CAD $90 million to CAD $2.5 billion.

Conclusion: Interventions targeting modifiable cancer risk factors could prevent a substantial number of incident cancer cases and billions of dollars in cancer management costs. With limited budgets and rising costs in cancer care in Canada, these simulation models and results are valuable for researchers and policymakers to inform decisions and prioritize and evaluate intervention programs.
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http://dx.doi.org/10.17269/s41997-021-00502-xDOI Listing
May 2021

Incidence of Pregnancy-Associated Cancer in Two Canadian Provinces: A Population-Based Study.

Int J Environ Res Public Health 2021 03 17;18(6). Epub 2021 Mar 17.

Department of Community Health Sciences, University of Calgary, Calgary, AB T2N 1N4, Canada.

Pregnancy-associated cancer-that is diagnosed in pregnancy or within 365 days after delivery-is increasingly common as cancer therapy evolves and survivorship increases. This study assessed the incidence and temporal trends of pregnancy-associated cancer in Alberta and Ontario-together accounting for 50% of Canada's entire population. Linked data from the two provincial cancer registries and health administrative data were used to ascertain new diagnoses of cancer, livebirths, stillbirths and induced abortions among women aged 18-50 years, from 2003 to 2015. The annual crude incidence rate (IR) was calculated as the number of women with a pregnancy-associated cancer per 100,000 deliveries. A nonparametric test for trend assessed for any temporal trends. In Alberta, the crude IR of pregnancy-associated cancer was 156.2 per 100,000 deliveries (95% CI 145.8-166.7), and in Ontario, the IR was 149.4 per 100,000 deliveries (95% CI 143.3-155.4). While no statistically significant temporal trend in the IR of pregnancy-associated cancer was seen in Alberta, there was a rise in Ontario ( = 0.01). Pregnancy-associated cancer is common enough to warrant more detailed research on maternal, pregnancy and child outcomes, especially as cancer therapies continue to evolve.
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http://dx.doi.org/10.3390/ijerph18063100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002657PMC
March 2021

Association of a Shortened Duration of Adjuvant Chemotherapy With Overall Survival Among Individuals With Stage III Colon Cancer.

JAMA Netw Open 2021 03 1;4(3):e213587. Epub 2021 Mar 1.

Oncology Outcomes Initiative, University of Calgary, Calgary, Alberta, Canada.

Importance: Several real-world oncology studies have produced findings that contradict those from randomized clinical trials. Such disparities may be associated with methodological shortcomings.

Objective: To examine the association between a shortened duration of adjuvant chemotherapy among individuals with stage III colon cancer using real-world data.

Design, Setting, And Participants: This comparative effectiveness study included individuals diagnosed with stage III colon cancer between January 2004 and December 2015 who initiated adjuvant chemotherapy at oncology clinics within the province of Alberta, Canada. Patients were identified through record linkage of various administrative databases and were followed up until September 2017. Eligibility criteria were modeled after those used in the International Duration Evaluation of Adjuvant (IDEA) trial. A target trial emulation and naive observational analysis were conducted. Results from both cohorts were benchmarked against findings from the IDEA trial. Data analysis was conducted from March to December 2020.

Exposure: A shortened duration of adjuvant 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX) or capecitabine plus oxaliplatin (CAPOX) chemotherapy, defined as 3 to 5 months of treatment vs 6 months.

Main Outcomes And Measures: Overall survival assessed via vital statistics. The per-protocol hazard ratio (HR) was estimated using a weighted pooled logistic regression model. Subgroup analyses were conducted by treatment regimen (ie, FOLFOX vs CAPOX) and cancer stage (ie, T1-3 and N1 vs T4 or N2).

Results: From an initial cohort of 3086 patients, 485 (16%) were eligible for inclusion in the target trial analysis. The median age was 59 years (range, 19-81 years), and 230 (47%) were women. The maximum follow-up was 11.6 years. Median overall survival was not reached. A total of 90 patients (19%) died. The 5-year Kaplan Meier overall survival estimate was 0.79 (95% CI, 0.75-0.84). Estimates from the trial emulation were similar to those from the IDEA trial. For example, a shortened duration of adjuvant chemotherapy was not associated with overall survival among patients prescribed CAPOX in the IDEA trial (HR, 0.96; 95% CI, 0.85-1.08) or in the trial emulation (HR, 0.96; 95% CI, 0.43-2.14). In contrast, the naive observational analysis suggested that a shortened duration of CAPOX was significantly associated with worse survival (HR, 3.33; 95% CI, 1.04-10.65).

Conclusions And Relevance: In this study, the explicit emulation of a target trial better approximated results from an analogous well-conducted randomized clinical trial.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.3587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010592PMC
March 2021

Comparative Success of Recruitment Strategies for an Exercise Intervention Trial Among Women With Polycystic Ovary Syndrome: Observational Study.

J Med Internet Res 2021 Mar 30;23(3):e25208. Epub 2021 Mar 30.

Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

Background: Effective and efficient participant recruitment is a key determinant of the success of a research program. Previously reported recruitment strategies have displayed variable success rates in studies on women with polycystic ovary syndrome (PCOS).

Objective: This study aimed to evaluate the effectiveness and cost per participant of the recruitment strategies that we used in a prospective randomized controlled trial to examine the effects of exercise training among inactive women with PCOS, who are aged 18-40 years.

Methods: The 4 recruitment methods we used were as follows: (1) referral by health care providers or by word of mouth, (2) media (eg, local newspaper stories and radio interviews), (3) Facebook advertisements, and (4) unpaid advertisements including posters and websites. The proportions of potential, eligible, and enrolled participants recruited with each method were determined and compared using tests of proportion. The time investment and cost per participant enrolled were calculated for each recruitment strategy.

Results: Of 200 potential participants screened, 98 (49%) were recruited from unpaid advertisements (posters and websites), 70 (35%) from Facebook advertisements, 16 (8%) by referral, and 16 (8%) from traditional media (newspaper and radio). Every potential participant was recruited from separate means (ie, no participant was approached through more than one recruitment method). A total of 109 (54.5%) women were deemed eligible for participation in the trial, and 60 (30.0%) were enrolled. The proportion of potential participants who completed the trial was higher for those recruited from traditional media than from Facebook advertisements (n=7/16, 44% vs n=13/70, 19%, respectively; P=.03) or unpaid advertisements (n=7/16, 44% vs n=13/98, 13%, respectively; P=.002). The cost per participant was Can $18.21 (US $14.46) for Facebook advertisements and Can $43.88 (US $34.85) for unpaid advertisements. There were no direct trial costs for referrals or traditional media.

Conclusions: For this trial, each method was important for recruiting inactive women with PCOS because no participant reported learning about the trial through more than one method. Unpaid advertisements and Facebook advertisements helped recruit the largest number of participants in the trial, the former resulting in a higher cost per participant than the latter.

Trial Registration: ClinicalTrials.gov NCT03362918; https://clinicaltrials.gov/ct2/show/NCT03362918.
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http://dx.doi.org/10.2196/25208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044737PMC
March 2021

Exercise and health-related fitness predictors of chemotherapy completion in breast cancer patients: pooled analysis of two multicenter trials.

Breast Cancer Res Treat 2021 Mar 29. Epub 2021 Mar 29.

University of Alberta, Edmonton, AB, Canada.

Purpose: Achieving a higher chemotherapy completion rate is associated with better outcomes in breast cancer patients. We examined the role of exercise and health-related fitness variables in predicting chemotherapy completion in early stage breast cancer patients.

Methods: We pooled data from two large, multicenter, exercise trials that obtained baseline (pre-chemotherapy) measures of exercise and health-related fitness in 543 breast cancer patients initiating adjuvant chemotherapy. Assessments included body composition, cardiovascular fitness, muscular strength, patient-reported physical functioning, and self-reported exercise behavior. Chemotherapy completion was assessed as the average relative dose intensity (RDI) for the originally planned regimen. We used logistic regression analyses with a two-sided p value of < 0.05 to estimate the associations between the predictors and an RDI of ≥ 85%.

Results: Overall, 432 of 543 (79.6%) breast cancer patients received an RDI of ≥ 85%. In logistic regression analyses adjusted for significant covariates, patients in the highest 20% vs. lowest 80% of absolute VO were significantly more likely to complete ≥ 85% RDI (89.0% vs. 77.2%; OR 2.06, 95% CI 1.07-3.96, p = 0.031). Moreover, patients in the highest 80% vs. lowest 20% of absolute chest strength were significantly more likely to complete ≥ 85% RDI (81.5% vs. 71.4%; OR 1.80, 95% CI 1.09-2.98, p = 0.021).

Conclusions: In these exploratory analyses, higher baseline (pre-chemotherapy) cardiovascular fitness and muscular strength were associated with higher rates of chemotherapy completion in early stage breast cancer patients. Aerobic and/or strength training interventions that increase cardiovascular fitness and muscular strength prior to chemotherapy for breast cancer may improve treatment tolerability and outcomes.

Clinical Trial Registration: START: NCT00115713, June 24, 2005; CARE: NCT00249015, November 7, 2005 ( http://clinicaltrials.gov ).
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http://dx.doi.org/10.1007/s10549-021-06205-8DOI Listing
March 2021

Adherence to a lower versus higher intensity physical activity intervention in the Breast Cancer & Physical Activity Level (BC-PAL) Trial.

J Cancer Surviv 2021 Mar 22. Epub 2021 Mar 22.

Department of Cancer Epidemiology and Prevention Research, Cancer Care Alberta, Alberta Health Services, Calgary, Alberta, Canada.

Purpose: The first aim is to examine adherence to a lower versus higher intensity physical activity (PA) prescription in breast cancer survivors in the Breast Cancer & Physical Activity Level (BC-PAL) Trial. The second aim is to assess associations between baseline characteristics with mean PA adherence in both intervention groups combined.

Methods: Forty-five participants were randomized to a 12-week, home-based lower (300 min/week, 40-59% heart rate reserve (HRR)) or higher (150 min/week, 60-80% HRR) intensity PA intervention, or no intervention/control. Both intervention groups received Polar A360® trackers and were included in this analysis (n=30). Study outcomes assessed on a weekly basis with the Polar A360® activity tracker throughout the intervention included relative adherence to the prescribed PA interventions (% of PA prescription goal met), and the absolute amount of PA time ≥40% of HRR. Baseline predictors of adherence included demographic characteristics, cardiorespiratory fitness, habitual PA and sedentary time, quality of life measures, and motivational variables from the Theory of Planned Behavior. For our primary aim, a linear mixed model was used to assess the effects of randomization group, time (intervention weeks 1-12), and the interaction of these factors on the natural logarithm of PA adherence. For our secondary aim, the association between each baseline predictor with the natural logarithm of mean weekly PA adherence was assessed, with randomization group added as a covariate.

Results: Higher relative time within the prescribed HRR zone was noted in the lower versus higher intensity PA groups (e=3.12, 95% CI=1.97, 4.95). No differences in adherence across time were noted. Social support was inversely associated with relative PA time within the prescribed HRR zone (e=0.83, 95% CI=0.72, 0.97) and absolute PA time ≥40% of HRR (e= 0.82, 95% CI: 0.71, 0.93). Baseline VO was inversely associated with relative PA adherence (e=0.98, 95% CI=0.95, 0.99). No other baseline measures were associated with PA adherence.

Conclusions: There were no significant changes in absolute PA time ≥40% of HRR across time or between groups. However, the lower intensity PA group averaged over 3 times the relative amount of PA within the prescribed HRR zone compared to the higher intensity PA group. Finally, lower peer support and cardiorespiratory fitness at baseline were associated with higher PA adherence.

Implications For Cancer Survivors: The recent rise in popularity of commercially available activity trackers provides new opportunities to promote PA participation remotely, and these devices can be used to continuously and objectively measure PA levels as an indicator of intervention adherence. Future studies are needed to explore baseline predictors, facilitators, and barriers to sustained activity tracker use to promote PA behavior change and intervention adherence in cancer survivors.

Trial Registration: This study was registered at www.clinicaltrials.gov (No. NCT03564899) on June 21, 2018.
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http://dx.doi.org/10.1007/s11764-021-01030-wDOI Listing
March 2021

Weight Regain and Breast Cancer-Related Biomarkers Following an Exercise Intervention in Postmenopausal Women.

Cancer Epidemiol Biomarkers Prev 2021 Jun 18;30(6):1260-1269. Epub 2021 Mar 18.

Department of Cancer Epidemiology and Prevention Research, Cancer Care Alberta, Alberta Health Services, Calgary, Alberta, Canada.

Background: Epidemiologic studies have reported associations between weight fluctuations and postmenopausal breast cancer risk; however, the biological markers involved in this association are unknown. This study aimed to explore the associations between breast cancer-related biomarkers and weight regain following exercise-induced weight loss.

Methods: From the 400 participants included in the Breast Cancer and Exercise Trial in Alberta, a total of 214 lost weight during the intervention and had follow-up blood samples, body composition, and covariate measurements. Outcomes were measured at baseline, 12 months (end of the study), and 24 months (follow-up).

Results: During follow-up, weight regain was 1.80 kg [95% confidence interval (CI): -0.40-3.90], and was significantly associated with increases in estradiol [treatment effect ratio (TER) = 1.03; 95% CI, 1.01-1.04], estrone (TER = 1.02; 95% CI, 1.01-1.03), free estradiol (TER = 1.04; 95% CI, 1.02-1.05), the homeostatic model assessment for insulin resistance (TER = 1.03; 95% CI, 1.02-1.05), and insulin (TER = 1.03; 95% CI, 1.01-1.04), and decreases in sex hormone-binding globulin (SHBG; TER = 0.98; 95% CI, 0.97-0.99) levels. Nonstatistically significant associations were found for glucose and C-reactive protein. Furthermore, a statistically significant linear trend of increasing levels for all biomarkers, and decreasing SHBG, across weight regain categories was found.

Conclusions: These results suggest that weight regain following exercise-induced weight loss is associated with breast cancer-related biomarker changes in postmenopausal women.

Impact: These findings provide evidence to support the importance of developing effective strategies to prevent weight regain and, consequently, decrease postmenopausal breast cancer risk via changes in adiposity-related biomarkers.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1652DOI Listing
June 2021

Dose-response effects of aerobic exercise on adiposity markers in postmenopausal women: pooled analyses from two randomized controlled trials.

Int J Obes (Lond) 2021 Jun 16;45(6):1298-1309. Epub 2021 Mar 16.

Department of Cancer Epidemiology and Prevention Research, Cancer Care Alberta, Alberta Health Services, Calgary, AB, Canada.

Background/objective: Exercise may reduce the risk of breast cancer through adiposity changes, but the dose-response effects of exercise volume on adiposity markers are unknown in postmenopausal women. We aimed to compare the dose-response effects of prescribed aerobic exercise volume on adiposity outcomes.

Participants/methods: Data from the Alberta Physical Activity and Breast Cancer Prevention (ALPHA) and Breast Cancer and Exercise Trial in Alberta (BETA) were pooled for this analysis (N = 720). These were 12-month randomized controlled trials, where participants were randomized to 225 min/week (mid-volume) of aerobic exercise versus usual inactive lifestyle (ALPHA), or 150 min/week (low-volume) versus 300 min/week (high-volume) (BETA). Fat mass and fat-free mass were measured using DXA and intra-abdominal and subcutaneous fat area were assessed with computed tomography.

Results: After 12 months of aerobic exercise, increasing exercise volumes from no exercise/control to 300 min/week resulted in statistically significant reductions in BMI, weight, fat mass, fat percentage, intra-abdominal and subcutaneous fat area (P < 0.001). Compared with controls, fat mass loss was -1.13, -1.98 and -2.09 kg in the low-, mid- and high-volume groups, respectively. Similarly, weight loss was -1.47, -1.83, -2.21 kg in the low-, mid- and high-volume groups, respectively, compared to controls, and intra-abdominal fat area loss was -7.44, -15.56 and -8.76 cm in the low-, mid- and high-volume groups, respectively, compared to controls. No evidence for a dose-response effect on fat-free mass was noted.

Conclusion: A dose-response effect of exercise volume on adiposity markers was noted, however, the differences in adiposity markers were smaller when comparing 225 min/week to 300 min/week of exercise. Given the strong positive associations between obesity and postmenopausal breast cancer risk, this study provides evidence on the importance of exercise volume as part of the exercise prescription to reduce adiposity and, ultimately, postmenopausal breast cancer risk.
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http://dx.doi.org/10.1038/s41366-021-00799-1DOI Listing
June 2021

Exercise training and reproductive outcomes in women with polycystic ovary syndrome: A pilot randomized controlled trial.

Clin Endocrinol (Oxf) 2021 Feb 27. Epub 2021 Feb 27.

Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

Objective: Exercise is recommended for polycystic ovary syndrome (PCOS), but the most effective exercise prescription is unclear. This trial compared effects of high-intensity interval training (HIIT), continuous aerobic exercise training (CAET) and no-exercise control on reproductive, anthropometric and cardiometabolic outcomes in PCOS.

Design: Pilot randomized controlled trial.

Participants: Previously inactive women aged 18-40 years with PCOS.

Measurements: Feasibility outcomes included recruitment, retention, adherence to exercise and daily ovulation prediction kit (OPK) testing. Preliminary efficacy outcomes included reproductive, anthropometric and cardiometabolic health markers.

Results: Forty-seven women were randomized to no-exercise control (n = 17), HIIT (n = 16), or CAET (n = 14). Forty (85%) participants completed the trial. Median exercise adherence was 68% (IQR 53%, 86%). Median daily OPK-testing adherence in the first half of the intervention was 87% (IQR 61%, 97%) compared with 65% (IQR 0%, 96%) in the second half. Body mass index decreased significantly in CAET compared with control (-1.0 kg/m , p = .01) and HIIT (-0.9 kg/m , p = .04). Mean waist circumference decreased in all groups (-7.3 cm, -6.9 cm, -4.5 cm in HIIT, CAET and control) with no significant between-group differences. Mean LDL-C was significantly reduced for HIIT compared to CAET (-0.33 mmol/L, p = .03). HDL-C increased in HIIT compared with control (0.18 mmol/L, p = .04).

Conclusions: There were feasibility challenges with adherence to daily ovulation assessment limiting the ability to analyse the effect of the exercise interventions on ovulation. CAET and HIIT were both effective at improving anthropometrics and some cardiometabolic health markers. Further studies need to determine optimal and acceptable exercise prescriptions for this population.
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http://dx.doi.org/10.1111/cen.14452DOI Listing
February 2021

The current burden of non-melanoma skin cancer attributable to ultraviolet radiation and related risk behaviours in Canada.

Cancer Causes Control 2021 Mar 4;32(3):279-290. Epub 2021 Jan 4.

Department of Public Health Sciences, Queen's University, Carruthers Hall, 62 Fifth Field Company Lane 2nd floor, Kingston, ON, K7L 3N6, Canada.

Purpose: Ultraviolet radiation (UVR) is an established cause of non-melanoma skin cancer (NMSC)-basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The aim of this study was to estimate the current burden of BCC and SCC associated with UVR and modifiable UVR behaviours (sunburn, sunbathing, and indoor tanning) in Canada in 2015.

Methods: The current burden of BCC and SCC associated with UVR was estimated by comparing 2015 incidence rates with rates of less exposed body sites (trunk and lower limbs) after adjusting for estimated surface areas. The burden associated with modifiable UVR behaviours was estimated by using prevalence estimates among Caucasians from the Second National Sun Survey, and relative risks that are generalizable to Canadians from conducting meta-analyses of relevant studies.

Results: We estimated that 80.5% of BCCs and 83.0% of SCCs were attributable to UVR. Adult sunburn was associated with relative risks of 1.85 (95% CI 1.15-3.00) for BCC and 1.41 (95% CI 0.91-2.18) for SCC, while adult sunbathing was associated with relative risks of 1.82 (95% CI 1.52-2.17) for BCC and 1.14 (95% CI 0.53-2.46) for SCC. We estimated that 18.6% of BCCs and 9.9% of SCCs were attributable to adult sunburn, while 28.1% of BCCs were attributable to adult sunbathing. We estimated that 46.2% of BCCs and 17.3% of SCCs were attributable to modifiable UVR behaviours combined.

Conclusion: Our results provide quantifiable estimates of the potentially avoidable burden of NMSCs among Canadians. These estimates can be used to motivate prevention efforts in Canada.
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http://dx.doi.org/10.1007/s10552-020-01382-1DOI Listing
March 2021

Global Public Health Guidelines on Physical Activity and Sedentary Behavior for People Living With Chronic Conditions: A Call to Action.

J Phys Act Health 2020 12 4;18(1):76-85. Epub 2020 Dec 4.

Background: In 2020, the World Health Organization (WHO) released global guidelines on physical activity (PA) and sedentary behavior, for the first time providing population-based recommendations for people living with selected chronic conditions. This article briefly presents the guidelines, related processes and evidence, and, importantly, considers how they may be used to support research, practice, and policy.

Methods: A brief overview of the scope, agreed methods, selected chronic conditions (adults living with cancer, hypertension, type 2 diabetes, and human immunodeficiency virus), and appraisal of systematic review evidence on PA/sedentary behavior is provided. Methods were consistent with World Health Organization protocols for developing guidelines.

Results: Moderate to high certainty evidence (varying by chronic condition and outcome examined) supported that PA can reduce the risk of disease progression or premature mortality and improve physical function and quality of life in adults living with chronic conditions. Direct evidence on sedentary behavior was lacking; however, evidence extrapolated from adult populations was considered applicable, safe, and likely beneficial (low certainty due to indirectness).

Conclusions: Clinical and public health professionals and policy makers should promote the World Health Organization 2020 global guidelines and develop and implement services and programs to increase PA and limit sedentary behavior in adults living with chronic conditions.
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http://dx.doi.org/10.1123/jpah.2020-0525DOI Listing
December 2020

World Health Organization 2020 guidelines on physical activity and sedentary behaviour.

Br J Sports Med 2020 Dec;54(24):1451-1462

Physical Activity Unit, Department of Health Promotion, World Health Organization, Geneva, Switzerland.

Objectives: To describe new WHO 2020 guidelines on physical activity and sedentary behaviour.

Methods: The guidelines were developed in accordance with WHO protocols. An expert Guideline Development Group reviewed evidence to assess associations between physical activity and sedentary behaviour for an agreed set of health outcomes and population groups. The assessment used and systematically updated recent relevant systematic reviews; new primary reviews addressed additional health outcomes or subpopulations.

Results: The new guidelines address children, adolescents, adults, older adults and include new specific recommendations for pregnant and postpartum women and people living with chronic conditions or disability. All adults should undertake 150-300 min of moderate-intensity, or 75-150 min of vigorous-intensity physical activity, or some equivalent combination of moderate-intensity and vigorous-intensity aerobic physical activity, per week. Among children and adolescents, an average of 60 min/day of moderate-to-vigorous intensity aerobic physical activity across the week provides health benefits. The guidelines recommend regular muscle-strengthening activity for all age groups. Additionally, reducing sedentary behaviours is recommended across all age groups and abilities, although evidence was insufficient to quantify a sedentary behaviour threshold.

Conclusion: These 2020 WHO guidelines update previous WHO recommendations released in 2010. They reaffirm messages that some physical activity is better than none, that more physical activity is better for optimal health outcomes and provide a new recommendation on reducing sedentary behaviours. These guidelines highlight the importance of regularly undertaking both aerobic and muscle strengthening activities and for the first time, there are specific recommendations for specific populations including for pregnant and postpartum women and people living with chronic conditions or disability. These guidelines should be used to inform national health policies aligned with the and to strengthen surveillance systems that track progress towards national and global targets.
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http://dx.doi.org/10.1136/bjsports-2020-102955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719906PMC
December 2020

Advancing the global physical activity agenda: recommendations for future research by the 2020 WHO physical activity and sedentary behavior guidelines development group.

Int J Behav Nutr Phys Act 2020 11 26;17(1):143. Epub 2020 Nov 26.

Physical Activity Unit, Department of Health Promotion, World Health Organization, Geneva, Switzerland.

Background: In July, 2019, the World Health Organization (WHO) commenced work to update the 2010 Global Recommendations on Physical Activity for Health and established a Guideline Development Group (GDG) comprising expert public health scientists and practitioners to inform the drafting of the 2020 Guidelines on Physical Activity and Sedentary Behavior. The overall task of the GDG was to review the scientific evidence and provide expert advice to the WHO on the amount of physical activity and sedentary behavior associated with optimal health in children and adolescents, adults, older adults (> 64 years), and also specifically in pregnant and postpartum women and people living with chronic conditions or disabilities.

Methods: The GDG reviewed the available evidence specific to each sub-population using systematic protocols and in doing so, identified a number of gaps in the existing literature. These proposed research gaps were discussed and verified by expert consensus among the entire GDG.

Results: Evidence gaps across population sub-groups included a lack of information on: 1) the precise shape of the dose-response curve between physical activity and/or sedentary behavior and several of the health outcomes studied; 2) the health benefits of light-intensity physical activity and of breaking up sedentary time with light-intensity activity; 3) differences in the health effects of different types and domains of physical activity (leisure-time; occupational; transportation; household; education) and of sedentary behavior (occupational; screen time; television viewing); and 4) the joint association between physical activity and sedentary time with health outcomes across the life course. In addition, we acknowledge the need to conduct more population-based studies in low- and middle-income countries and in people living with disabilities and/or chronic disease, and to identify how various sociodemographic factors (age, sex, race/ethnicity, socioeconomic status) modify the health effects of physical activity, in order to address global health disparities.

Conclusions: Although the 2020 WHO Guidelines for Physical Activity and Sedentary Behavior were informed by the most up-to-date research on the health effects of physical activity and sedentary time, there is still substantial work to be done in advancing the global physical activity agenda.
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http://dx.doi.org/10.1186/s12966-020-01042-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690200PMC
November 2020

New global guidelines on sedentary behaviour and health for adults: broadening the behavioural targets.

Int J Behav Nutr Phys Act 2020 11 26;17(1):151. Epub 2020 Nov 26.

Physical Activity Unit, Department of Health Promotion, World Health Organization, Geneva, Switzerland.

Background: In 2018, the World Health Organisation (WHO) commenced a program of work to update the 2010 Global Recommendations on Physical Activity for Health, for the first-time providing population-based guidelines on sedentary behaviour. This paper briefly summarizes and highlights the scientific evidence behind the new sedentary behaviour guidelines for all adults and discusses its strengths and limitations, including evidence gaps/research needs and potential implications for public health practice.

Methods: An overview of the scope and methods used to update the evidence is provided, along with quality assessment and grading methods for the eligible new systematic reviews. The literature search update was conducted for WHO by an external team and reviewers used the AMSTAR 2 (Assessment of Multiple Systematic Reviews) tool for critical appraisal of the systematic reviews under consideration for inclusion. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was used to rate the certainty (i.e. very low to high) of the evidence.

Results: The updated systematic review identified 22 new reviews published from 2017 up to August 2019, 14 of which were incorporated into the final evidence profiles. Overall, there was moderate certainty evidence that higher amounts of sedentary behaviour increase the risk for all-cause, cardiovascular disease (CVD) and cancer mortality, as well as incidence of CVD, cancer, and type 2 diabetes. However, evidence was deemed insufficient at present to set quantified (time-based) recommendations for sedentary time. Moderate certainty evidence also showed that associations between sedentary behaviour and all-cause, CVD and cancer mortality vary by level of moderate-to-vigorous physical activity (MVPA), which underpinned additional guidance around MVPA in the context of high sedentary time. Finally, there was insufficient or low-certainty systematic review evidence on the type or domain of sedentary behaviour, or the frequency and/or duration of bouts or breaks in sedentary behaviour, to make specific recommendations for the health outcomes examined.

Conclusions: The WHO 2020 guidelines are based on the latest evidence on sedentary behaviour and health, along with interactions between sedentary behaviour and MVPA, and support implementing public health programmes and policies aimed at increasing MVPA and limiting sedentary behaviour. Important evidence gaps and research opportunities are identified.
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http://dx.doi.org/10.1186/s12966-020-01044-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691115PMC
November 2020

Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers.

Cancer Epidemiol Biomarkers Prev 2021 01 3;30(1):217-228. Epub 2020 Nov 3.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.

Background: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers.

Methods: Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data.

Results: Genetic correlation analysis revealed significant genetic correlation between the two cancers ( = 0.43, = 2.66 × 10). We found seven loci associated with risk for both cancers ( < 2.4 × 10). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified ( < 5 × 10). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation.

Conclusions: Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis.

Impact: Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0739DOI Listing
January 2021

Development of a Model for Predicting Early Discontinuation of Adjuvant Chemotherapy in Stage III Colon Cancer.

JCO Clin Cancer Inform 2020 10;4:972-984

Department of Oncology, Cumming School of Medicine, University of Calgary, Alberta, Canada.

Purpose: To develop a tool that can be used to predict early discontinuation of adjuvant chemotherapy among patients with stage III colon cancer.

Patients And Methods: Through record linkage of Alberta administrative and tumor registry databases, we identified a cohort of individuals age ≥ 18 years who were diagnosed with stage III colon cancer and who received adjuvant chemotherapy in Alberta between 2004 and 2015. Early discontinuation was defined as receipt of < 5 months of a planned 6-month course of chemotherapy. By a systematic review of the literature and a survey of medical oncologists, the following candidate variables were identified: age (years), number of comorbidities (0, 1, ≥ 2), cancer stage (IIIC IIIA-B), type of chemotherapy (fluorouracil, leucovorin, and oxaliplatin; capecitabine and oxaliplatin; or monotherapy), time from surgery to chemotherapy initiation (weeks), type of treatment facility (academic or community), and distance from home to treatment center (kilometers). Models developed using penalized logistic regression and the random forest algorithm were compared. Model performance was assessed using the C-statistic, Brier score, and a calibration plot. Internal validation was performed using the bootstrap method.

Results: From an initial 3,115 patients identified, 1,378 were deemed eligible for inclusion. Of these patients, 474 patients (34.4%) failed to complete at least 5 months of chemotherapy. Although well calibrated, the penalized logistic regression model had poor discrimination (optimism-adjusted C-statistic, 0.63; 95% CI, 0.60 to 0.67). In contrast, the random forest model achieved adequate discrimination (optimism-adjusted C-statistic, 0.80; 95% CI, 0.79 to 0.82). Although the degree of calibration of the random forest was acceptable, it was slightly worse than that of the penalized logistic regression model.

Conclusion: Internal validation of our random forest model suggests that it may have clinical utility. Additional research regarding its external validation and clinical impact is needed.
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http://dx.doi.org/10.1200/CCI.20.00065DOI Listing
October 2020

Pregnancy outcomes and risk of endometrial cancer: A pooled analysis of individual participant data in the Epidemiology of Endometrial Cancer Consortium.

Int J Cancer 2021 May 17;148(9):2068-2078. Epub 2020 Nov 17.

Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.

A full-term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy-related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case-control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16 986 women with endometrial cancer and 39 538 control women. We used one- and two-stage meta-analytic approaches to estimate pooled odds ratios (ORs) for the association between exposures and endometrial cancer risk. Ever having a full-term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full-term pregnancy (OR = 0.59, 95% confidence interval [CI] 0.56-0.63). The risk reduction appeared the greatest for the first full-term pregnancy (OR = 0.78, 95% CI 0.72-0.84), with a further ~15% reduction per pregnancy up to eight pregnancies (OR = 0.20, 95% CI 0.14-0.28) that was independent of age at last full-term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7%-9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full-term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full-term pregnancy. These results suggest that the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.
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http://dx.doi.org/10.1002/ijc.33360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969437PMC
May 2021

Prospective Cohort Study of Pre- and Postdiagnosis Physical Activity and Endometrial Cancer Survival.

J Clin Oncol 2020 12 7;38(34):4107-4117. Epub 2020 Oct 7.

Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, Canada.

Purpose: The aim of this study was to evaluate associations between pre- and postdiagnosis physical activity and survival in survivors of endometrial cancer by physical activity domain, intensity, dose (metabolic-equivalent task [MET]-hours/week/year), and change from pre- to postdiagnosis.

Methods: We conducted a prospective cohort study in Alberta, Canada, of 425 women who were diagnosed with histologically confirmed invasive endometrial cancer between 2002 and 2006 and observed to 2019. The interviewer-administered Lifetime Total Physical Activity Questionnaire recorded prediagnosis (assessed at a median of 4.4 months after diagnosis) and postdiagnosis physical activity (assessed at a median of 3.4 years after diagnosis). Associations between physical activity and overall and disease-free survival were assessed using Cox proportional hazards models adjusted for age, stage, grade, treatments, body mass index, menopausal status, hormone therapy use, family history of cancer, and comorbidities.

Results: After a median follow-up of 14.5 years, there were 60 deaths, including 18 endometrial cancer deaths, and 80 disease-free survival events. Higher prediagnosis recreational physical activity was statistically significantly associated with improved disease-free survival (> 14 ≤ 8 MET-hours/week/year; hazard ratio [HR], 0.54; 95% CI, 0.30 to 0.96; = .04), but not overall survival (HR, 0.56; 95% CI, 0.29 to 1.07; = .06). Higher postdiagnosis recreational physical activity (> 13 ≤ 5 MET-hours/week/year) was strongly associated with both improved disease-free survival (HR, 0.33; 95% CI, 0.17 to 0.64; = .001) and overall survival (HR, 0.33; 95% CI, 0.15 to 0.75; = .007). Participants who maintained high recreational physical activity levels from pre- to postdiagnosis also had improved disease-free survival (HR, 0.35; 95% CI, 0.18 to 0.69) and overall survival (HR, 0.43; 95% CI, 0.20 to 0.94) compared with those who maintained low physical activity levels.

Conclusion: Recreational physical activity, especially postdiagnosis, is associated with improved survival in survivors of endometrial cancer.
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http://dx.doi.org/10.1200/JCO.20.01336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768343PMC
December 2020

High-sensitivity C-reactive protein, hemoglobin A1c and breast cancer risk: a nested case-control study from Alberta's Tomorrow Project cohort.

Cancer Causes Control 2020 Dec 21;31(12):1057-1068. Epub 2020 Sep 21.

Department of Cancer Epidemiology and Prevention Research, Alberta Health Services, Calgary, AB, Canada.

Purpose: Our aim is to examine the associations between high-sensitivity C-reactive protein (hsCRP) and hemoglobin A1c (HbA1c), common biomarkers of inflammation and insulin resistance, respectively, with breast cancer risk, while adjusting for measures of excess body size.

Methods: We conducted a nested case-control study within the Alberta's Tomorrow Project cohort (Alberta, Canada) including 197 incident breast cancer cases and 394 matched controls. The sample population included both pre- and postmenopausal women. Serum concentrations of hsCRP and HbA1c were measured from blood samples collected at baseline, along with anthropometric measurements, general health and lifestyle data. Conditional logistic regression was used to evaluate associations between hsCRP, HbA1c, and breast cancer risk adjusted for excess body size (body fat percentage) and other risk factors for breast cancer.

Results: Higher concentrations of hsCRP were associated with elevated breast cancer risk (odds ratio [OR] 1.27; 95% confidence interval [95% CI] 1.03-1.55). The observed associations were unchanged with adjustment for body fat percentage. Higher HbA1c concentrations were not significantly associated with an increased breast cancer risk (OR 1.22; 95% CI 0.17-8.75).

Conclusion: These data suggest that hsCRP may be associated with elevated breast cancer risk, independent of excess body size. However, elevated concentrations of HbA1c did not appear to increase breast cancer risk in apparently healthy women.
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http://dx.doi.org/10.1007/s10552-020-01329-6DOI Listing
December 2020

Effects of a wearable technology-based physical activity intervention on sleep quality in breast cancer survivors: the ACTIVATE Trial.

J Cancer Surviv 2021 Apr 1;15(2):273-280. Epub 2020 Sep 1.

Cancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, VIC, 3004, Australia.

Introduction: Physical activity interventions can improve sleep quality in breast cancer survivors. This paper examines the effects of the ACTIVATE Trial, a wearable-based physical activity intervention (Garmin Vivofit2® coupled with behavioral feedback, goal setting, and health coaching) on sleep outcomes.

Methods: Post-primary treatment, inactive, postmenopausal breast cancer survivors were recruited and randomized to primary intervention or waitlist. Wrist-worn actigraphy (sleep onset latency, SOL; total sleep time, TST; sleep efficiency, SE; wake after sleep onset, WASO; and number of awakenings, NWAKE) and questionnaire-derived sleep measures (Pittsburgh Sleep Quality Index) were assessed at baseline (T1), 12 weeks (end of primary intervention and start of waitlist intervention, T2), and at 24 weeks (T3).

Results: Eighty-three women (mean age = 62 years) were randomized; trial retention was 94% at T2 and 87% at T3. At T2, primary intervention participants had greater improvements in WASO (- 5.7 min, 95% CI - 11.7 to - 0.2) and NWAKE compared with the waitlist arm (- 2.0, 95% CI - 3.6 to - 0.4). At T3, within-group improvements were observed for SE (both groups), WASO (both groups), NWAKE (primary intervention group only), total PSQI score (primary intervention group), and sleep efficacy (primary intervention group).

Conclusions: The intervention reduced actigraphy-measured sleep disturbances. Within-group analyses suggest that improvements in sleep quality are sustained over a longer duration, and there may be similar benefits from an abridged intervention (wearable device only). Actigraphy-measured effects appeared stronger in participants who were poor sleepers at study entry.

Implications For Cancer Survivors: Wearable technology can increase physical activity and improve sleep for breast cancer survivors.
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http://dx.doi.org/10.1007/s11764-020-00930-7DOI Listing
April 2021

Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer.

Int J Cancer 2021 01 7;148(2):307-319. Epub 2020 Aug 7.

Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia, USA.

Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two-sample Mendelian randomization analysis to investigate the relationship between levels of three blood lipids (low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol, and triglycerides) and endometrial cancer risk. Genetic variants associated with each of these blood lipid levels (P < 5 × 10 ) were identified as instrumental variables, and assessed using genome-wide association study data from the Endometrial Cancer Association Consortium (12 906 cases and 108 979 controls) and the Global Lipids Genetic Consortium (n = 188 578). Mendelian randomization analyses found genetically raised LDL cholesterol levels to be associated with lower risks of endometrial cancer of all histologies combined, and of endometrioid and non-endometrioid subtypes. Conversely, higher genetically predicted HDL cholesterol levels were associated with increased risk of non-endometrioid endometrial cancer. After accounting for the potential confounding role of obesity (as measured by genetic variants associated with body mass index), the association between genetically predicted increased LDL cholesterol levels and lower endometrial cancer risk remained significant, especially for non-endometrioid endometrial cancer. There was no evidence to support a role for triglycerides in endometrial cancer development. Our study supports a role for LDL and HDL cholesterol in the development of non-endometrioid endometrial cancer. Further studies are required to understand the mechanisms underlying these findings.
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http://dx.doi.org/10.1002/ijc.33206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757859PMC
January 2021

Associations between the built environment and physical activity among adults with low socio-economic status in Canada: a systematic review.

Can J Public Health 2021 02 24;112(1):152-165. Epub 2020 Aug 24.

Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, TRW 3rd floor, 3280 Hospital Drive NW, Calgary, Alberta, T2N 4Z6, Canada.

Objective: To synthesize literature on the associations between the built environment and physical activity among adults with low socio-economic status (SES) in Canada.

Methods: Using a pre-specified study protocol (PROSPERO ID: CRD42019117894), we searched seven databases from inception to November 2018, for peer-reviewed quantitative studies that (1) included adults with low SES living in Canada and (2) estimated the association between self-reported or objectively measured built characteristics and self-reported or objectively measured physical activity. Study quality was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Findings were synthesized using a narrative approach.

Synthesis: Of the 8338 citations identified by our search, seven studies met the inclusion criteria. Most studies included adults living in one province (Alberta, British Columbia, Ontario, or Quebec), with one study including a national sample. All studies were cross-sectional, and none controlled for residential self-selection. Sampling designs and data collection strategies were heterogeneous. Sample sizes ranged between 78 and 37,241 participants. Most studies measured SES using household income. Street connectivity, greenness, destination density, and walkability were positively associated with physical activity. Relative to the objectively measured built environment, associations between the self-reported built environment and physical activity were less consistent. Studies were of fair to good quality.

Conclusion: Findings suggest that the neighbourhood built environment is associated with physical activity among adults with low SES in Canada. More rigorous study designs are needed to determine whether or not the built environment and physical activity are causally related within this vulnerable population.
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http://dx.doi.org/10.17269/s41997-020-00364-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851286PMC
February 2021

Physical activity, obesity and sedentary behavior in cancer etiology: epidemiologic evidence and biologic mechanisms.

Mol Oncol 2021 Mar 18;15(3):790-800. Epub 2020 Aug 18.

Department of Cancer Epidemiology and Prevention Research, CancerControl Alberta, Alberta Health Services, Calgary, AB, Canada.

An estimated 30-40% of cancers can be prevented through changes in modifiable lifestyle and environmental risk factors known to be associated with cancer incidence. Despite this knowledge, there remains limited awareness that these associations exist. The purpose of this review article was to summarize the epidemiologic evidence concerning the contribution of physical activity, sedentary behavior, and obesity to cancer etiology and to provide an overview of the biologic mechanisms that may be operative between these factors and cancer incidence. Strong and consistent evidence exists that higher levels of physical activity reduce the risk of six different cancer sites (bladder, breast, colon, endometrial, esophageal adenocarcinoma, gastric cardia), whereas moderate evidence inversely associates physical activity with lung, ovarian, pancreatic and renal cancer, and limited evidence inversely correlates physical activity with prostate cancer. Sedentary behavior, independent of physical activity, has been shown to increase the risk of colon, endometrial, and lung cancers. Obesity is an established risk factor for 13 different cancer sites (endometrial, postmenopausal breast, colorectal, esophageal, renal/kidneys, meningioma, pancreatic, gastric cardia, liver, multiple myeloma, ovarian, gallbladder, and thyroid). The main biologic mechanisms whereby physical activity, sedentary behavior, and obesity are related to cancer incidence include an effect on endogenous sex steroids and metabolic hormones, insulin sensitivity, and chronic inflammation. Several emerging pathways related to oxidative stress, DNA methylation, telomere length, immune function, and gut microbiome are presented. Key recommendations for future research in both the epidemiology and biology of the associations between physical activity, sedentary behavior, obesity, and cancer risk are also provided.
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http://dx.doi.org/10.1002/1878-0261.12772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931121PMC
March 2021

Prospective cohort study of metabolic syndrome and endometrial cancer survival.

Gynecol Oncol 2020 09 27;158(3):727-733. Epub 2020 Jun 27.

Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Cancer Epidemiology and Prevention Research, CancerControl Alberta, Alberta Health Services, Calgary, Alberta, Canada; Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. Electronic address:

Objective: Comorbidities are known to increase endometrial cancer risk, but the separate and combined impact of these risk factors on endometrial cancer survival remains unclear. This study aimed to determine the associations between metabolic syndrome and its components with disease-free survival, overall survival, endometrial cancer-specific survival and recurrence among endometrial cancer survivors.

Methods: Cases from a population-based case-control study who were diagnosed with primary endometrial cancer between 2002 and 2006 in Alberta, Canada were followed until death or March 20, 2019. Baseline in-person interviews, direct anthropometric measurements and fasting blood samples were used to assess metabolic syndrome (presence of ≥3 of the following: waist circumference ≥ 88 cm, fasting blood glucose ≥100 mg/dL, triglycerides ≥150 mg/dL, high-density lipoprotein cholesterol <50 mg/dL and self-reported hypertension). Cox proportional hazards regression and Fine and Gray competing risk models were used to estimate multivariate-adjusted hazard ratios (95% CI) for these associations.

Results: Among 540 endometrial cancer survivors, 325 had metabolic syndrome at diagnosis and 132 had a recurrence and/or died during the median 14.2 years of follow-up (range: 0.3-16.5 years). In multivariable analyses, being diagnosed with metabolic syndrome (HR = 1.98, 95% CI = 1.07-3.67) and having an elevated waist circumference (≥88 cm; HR = 2.12, 95% CI = 1.18-3.80; HR = 1.21, 95% CI = 1.07-1.36) were associated with worse overall survival. Additionally, increasing waist circumference (per 5 cm) was also associated worse with disease-free survival (HR = 1.11, 95% CI = 1.00-1.24).

Conclusion: The metabolic syndrome, in particular central adiposity, were associated with worse overall and disease-free survival in endometrial cancer survivors.
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http://dx.doi.org/10.1016/j.ygyno.2020.06.488DOI Listing
September 2020

The effects of shift work and sleep duration on cancer incidence in Alberta`s Tomorrow Project cohort.

Cancer Epidemiol 2020 08 25;67:101729. Epub 2020 May 25.

Department of Cancer Epidemiology and Prevention Research, CancerControl Alberta, Alberta Health Services, Calgary, Alberta, Canada; Departments of Oncology and Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. Electronic address:

Introduction: We investigated the main effects of shift work and sleep duration on cancer incidence, and effect modification of the shift work-cancer incidence association by sleep duration.

Methods: Shift work and sleep duration were assessed among 21,804 participants from Alberta`s Tomorrow Project. Incident cases of breast, prostate, colorectal and lung cancers were identified through registry linkage.

Results: Having worked ≥6 years of rotating shift work (HR = 1.59, 95 % CI = 1.07, 2.37; P = 0.02) and having ever worked night shifts were associated with an increased risk of lung cancer (HR=1.71, 95 % CI=1.18, 2.47; P = 0.01), whereas having ever worked night shifts was associated with a reduced risk of prostate cancer in the latency-adjusted model only (HR=0.70, 95 % CI=0.51, 0.98; P = 0.04). No associations were found between shift work or sleep duration on the risks of breast and colorectal cancers. Some evidence of effect modification by sleep duration for the rotating shift work-lung cancer incidence association was noted (P = 0.06), with stratified analyses revealing borderline increased risk of lung cancer in participants with ≥6 years of rotating shift work and <7 h of sleep/day (HR=2.27, 95 % CI=0.95, 5.41; P = 0.07), and an increased risk of lung cancer in participants with 0.1-5.9 years of rotating shift work and >9 h of sleep/day (HR=2.99, 95 % CI=1.12, 7.97; P = 0.03). No additional evidence of effect modification by sleep duration for shift work and cancer incidence was noted.

Discussion: A consistent association between shift work employment and lung cancer risk was noted in this Canadian sample. Furthermore, some evidence of effect modification of the rotating shift work-lung cancer risk association by sleep duration was noted.
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http://dx.doi.org/10.1016/j.canep.2020.101729DOI Listing
August 2020

Physical Activity and Mortality in Cancer Survivors: A Systematic Review and Meta-Analysis.

JNCI Cancer Spectr 2020 Feb 17;4(1):pkz080. Epub 2019 Oct 17.

Institute of Health and Biomedical Innovation, School of Public Health and Social Work, Queensland University of Technology, Brisbane, Australia.

Background: Recommendations for improved survival after cancer through physical activity (PA) exist, although the evidence is still emerging. Our primary objective was to conduct a systematic review and meta-analysis of the association between prediagnosis and postdiagnosis PA and survival (cancer-specific, all-cause, and cardiovascular disease mortality) for all cancers and by tumor site. Secondary objectives were to examine the associations within population subgroups, by PA domain, and to determine the optimal dose of PA related to survival.

Methods: PubMed, EMBASE, and SportsDiscus databases were searched from inception to November 1, 2018. DerSimonian-Laird random-effects models were used to estimate the summary hazard ratios (HRs) and 95% confidence intervals (CI) for primary and secondary analyses and to conduct dose-response analyses.

Results: Evidence from 136 studies showed improved survival outcomes with highest vs lowest levels of prediagnosis or postdiagnosis total or recreational PA for all-cancers combined (cancer specific mortality: HR = 0.82, 95% CI = 0.79 to 0.86, and HR = 0.63, 95% CI = 0.53 to 0.75, respectively) as well as for 11 specific cancer sites. For breast and colorectal cancers, greater reductions were observed for postdiagnosis PA (HR = 0.58-0.63) compared with prediagnosis PA (HR = 0.80-0.86) for cancer-specific and all-cause mortality. Survival benefits through PA were observed in most subgroups (within sex, body mass index, menopausal status, colorectal subtypes, and PA domain) examined. Inverse dose-response relationships between PA and breast cancer-specific and all-cause mortality were observed, with steep reductions in hazards to 10-15 metabolic equivalent hours per week.

Conclusion: Higher prediagnosis and postdiagnosis levels of PA were associated with improved survival outcomes for at least 11 cancer types, providing support for global promotion of PA guidelines following cancer.
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http://dx.doi.org/10.1093/jncics/pkz080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050161PMC
February 2020

Exercise type and fat mass loss regulate breast cancer-related sex hormones in obese and overweight postmenopausal women.

Eur J Appl Physiol 2020 Jun 7;120(6):1277-1287. Epub 2020 Apr 7.

Department of Biomedical Sciences. Faculty of Medicine and Health Sciences, University of Alcalá, Ctra. Madrid-Barcelona km 33,600, 28805, Alcalá de Henares, Madrid, Spain.

Purpose: The aim of the study was to examine the effects of a time-matched endurance versus concurrent training on circulating sex hormone levels and body composition in postmenopausal women.

Methods: Thirty-five sedentary and obese postmenopausal women were recruited and randomly divided into endurance training (EN, n = 10), concurrent training (CON, n = 13), or control group (C, n = 12). Participants took part in a 12-week supervised intervention, training 3 days/week and 60 min/session. Before and after the intervention, body composition was assessed, and blood samples were obtained to evaluate estradiol, testosterone, DHEA-S, and SHBG.

Result: In response to training, a reduction in total fat mass was found (5.3%; P < 0.05), while an increase in lean body mass was observed in the CON group (1.5%; P < 0.05). There was a significant decrease in DHEA-S (- 13%), total (- 40%) and free testosterone (- 41%) in the EN group, while in the CON group, total (25%) and free testosterone (21%) increased significantly (P < 0.05). When participants were stratified according to fat mass loss (> or < 2 kg), a statistically significant increase in circulating SHBG (21%) and decrease in DHEA-S (- 13%) were found.

Conclusion: The type of exercise and exercise-induced fat mass loss seem to modify the sex hormone profile in postmenopausal women that is an established risk factor of breast cancer. Thus, this study provides additional evidences to the intricated interaction among sex hormones, adipose tissue, and muscle mass in postmenopausal women.
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http://dx.doi.org/10.1007/s00421-020-04361-1DOI Listing
June 2020

Corrigendum to "Estimates of the current and future burden of cancer attributable to lack of physical activity in Canada" [Prev. Med. 122 (2019) 65-72].

Prev Med 2020 Mar 3:106045. Epub 2020 Mar 3.

Department of Cancer Epidemiology and Prevention Research, CancerControl Alberta, Alberta Health Services, Calgary, Alberta, Canada; Departments of Oncology and Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

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http://dx.doi.org/10.1016/j.ypmed.2020.106045DOI Listing
March 2020

Patterns and predictors of exercise behavior during 24 months of follow-up after a supervised exercise program during breast cancer chemotherapy.

Int J Behav Nutr Phys Act 2020 02 14;17(1):23. Epub 2020 Feb 14.

Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, T6G 2H9, Canada.

Background: Understanding the longer-term exercise behavior of patients with breast cancer after chemotherapy is important to promote sustained exercise. The purpose of the current study was to report the longer-term patterns and predictors of exercise behavior in patients with breast cancer who exercised during chemotherapy.

Methods: In the Combined Aerobic and Resistance Exercise (CARE) Trial, 301 patients with breast cancer were randomized to three different exercise prescriptions during chemotherapy. Exercise behaviors after chemotherapy were self-reported at 6-, 12-, and 24-month follow-up. Exercise patterns were identified by categorizing patients according to which exercise guideline they were meeting (neither, aerobic only, resistance only, or combined) at each of the three follow-up timepoints (64 possible patterns). Predictors of longer-term exercise behavior included physical fitness, patient-reported outcomes, and motivational variables from the theory of planned behavior assessed at postintervention (postchemotherapy). Univariate and multivariate stepwise multinomial logistic regression and linear regression were used for statistical analyses.

Results: A total of 264 (88%) participants completed all three follow-up exercise behavior assessments and exhibited 50 different exercise patterns. Postintervention aerobic fitness was the most consistent predictor of longer-term exercise behavior at all three timepoints. For example, higher aerobic fitness (per 1 ml/kg/min) predicted better adherence to the "aerobic only" (OR = 1.09; p = 0.005) and "combined" (OR = 1.12; p < 0.001) guidelines compared to "neither" guideline at 6-month follow-up. Additionally, higher postintervention muscular strength (per 1 kg) was associated with better adherence to the "resistance only" (OR = 1.07; p = 0.025) and "combined" (OR = 1.08; p < 0.001) guidelines compared to "neither" guideline at 24-month follow-up. Finally, lower perceived difficulty (per 1 scale point) was associated with better adherence to the "combined" (OR = 0.62; p = 0.010) and "aerobic only" (OR = 0.58; p = 0.002) guideline compared to the "neither" guideline at the 24-month follow-up.

Conclusions: Our study is the first to show that the longer-term exercise patterns of patients with breast cancer who exercised during chemotherapy are diverse and predicted by physical fitness and motivational variables after chemotherapy. Our novel implications are that improving physical fitness during chemotherapy and applying motivational counseling after chemotherapy may improve longer-term exercise behavior in patients with breast cancer.

Trial Registration: (NCT00249015).
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http://dx.doi.org/10.1186/s12966-020-00924-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023725PMC
February 2020