Eileen Shaw

Inflammatory Marker Changes in Postmenopausal Women after a Year-long Exercise Intervention Comparing High Versus Moderate Volumes

This randomized dose comparison trial examined if higher exercise volume decreased inflammatory biomarkers, associated with postmenopausal breast cancer risk, more than moderate exercise volume. The Breast Cancer and Exercise Trial in Alberta was a two-center, two-armed randomized trial in 400 inactive, healthy, postmenopausal women, aged 50 to 74 years, with a body mass index of 22 to 40 kg/m2. Participants were randomized to high (300 minutes/week) or moderate (150 minutes/week) volumes of aerobic exercise while maintaining usual diet. Fasting blood concentrations of C-reactive protein (CRP), IL6, and TNFα were measured at baseline, 6 and 12 months. Intention-to-treat (ITT) analysis was performed using linear mixed models adjusted for baseline biomarker concentrations. ITT analyses of 386 (97%) participants showed no statistically significant group differences for changes in biomarker levels at 6 and 12 months. In addition, we did not observe any modification of this effect by baseline characteristics of participants. In post hoc analyses based on self-selected exercise level (measured in minutes/week), CRP decreased by 22.45% for participants who exercised >246 minutes/week (highest quintile) and increased by 0.07% for those who exercised <110 minutes/week (lowest quintile, Ptrend = 0.04), adjusted for baseline covariates. When this analysis was restricted to include exercise time in the target heart rate zone only, statistically significant trends were observed for both CRP (P < 0.01) and IL6 (P = 0.04). Prescribing 300 minutes/week of moderate-to-vigorous aerobic exercise did not improve inflammatory markers compared with 150 minutes/week in postmenopausal women. Decreases in CRP were observed with higher self-selected exercise volume. Cancer Prev Res; 9(2); 196–203. ©2015 AACR.

Epidemiology and biology of physical activity and cancer recurrence

Physical activity is emerging from epidemiologic research as a lifestyle factor that may improve survival from colorectal, breast, and prostate cancers. However, there is considerably less evidence relating physical activity to cancer recurrence and the biologic mechanisms underlying this association remain unclear. Cancer patients are surviving longer than ever before, and fear of cancer recurrence is an important concern. Herein, we provide an overview of the current epidemiologic evidence relating physical activity to cancer recurrence. We review the biologic mechanisms most commonly researched in the context of physical activity and cancer outcomes, and, using the example of colorectal cancer, we explore hypothesized mechanisms through which physical activity might intervene in the colorectal recurrence pathway. Our review highlights the importance of considering pre-diagnosis and post-diagnosis activity, as well as cancer stage and timing of recurrence, in epidemiologic studies. In addition, more epidemiologic research is needed with cancer recurrence as a consistently defined outcome studied separately from survival. Future mechanistic research using randomized controlled trials, specifically those demonstrating the exercise responsiveness of hypothesized mechanisms in early stages of carcinogenesis, are needed to inform recommendations about when to exercise and to anticipate additive or synergistic effects with other preventive behaviors or treatments.

Effects of exercise on markers of oxidative stress: an Ancillary analysis of the Alberta Physical Activity and Breast Cancer Prevention Trial

Background Oxidative stress may contribute to cancer aetiology through several mechanisms involving damage to DNA, proteins and lipids leading to genetic mutations and genomic instability. The objective of this study was to determine the effects of aerobic exercise on markers of oxidative damage and antioxidant enzymes in postmenopausal women. Methods The Alberta Physical Activity and Breast Cancer Prevention Trial (ALPHA) was a two-centre, two-armed randomised trial of 320 inactive, healthy, postmenopausal women aged 50–74 years. Participants were randomly assigned to a year-long exercise intervention (225 min/week) or a control group while being asked to maintain a normal diet. Fasting blood samples were obtained and plasma concentrations of two oxidative damage markers (8-hydroxy-2′-deoxyguanosine (8-OHdG) and 8-isoprostaglandin F2α (8-Iso-PGF2α)) and two antioxidant enzymes (superoxide dismutase and catalase) were measured at baseline, 6 months and 12 months. Intention-to-treat (ITT) and per-protocol analyses were performed using linear mixed models adjusted for baseline biomarker concentrations. A further exercise adherence analysis, based on mean minutes of exercise per week, was also performed. Results In the ITT and per-protocol analyses, the exercise intervention did not have any statistically significant effect on either oxidative damage biomarkers or antioxidant enzyme activity. Conclusions A year-long aerobic exercise intervention did not have a significant impact on oxidative stress in healthy, postmenopausal women. Trial registration number NCT00522262.

Increasing colorectal cancer incidence trends among younger adults in Canada

Recent analyses in the United States have shown an overall decrease in the incidence of colorectal cancer despite contrasting increases in younger age groups. We examined whether these cohort trends are occurring in Canada. Age-specific trends in colon and rectal cancer incidence in Canada from the National Cancer Incidence Reporting System (1969-1992) and the Canadian Cancer Registry (1992-2012) were analyzed. We estimated annual percent changes (APC) with the Joinpoint Regression Program from the Surveillance Epidemiology, and End Results Program. Birth cohort effects were estimated using 5-year groups starting in 1888. Age-specific prevalence of class I, II and III obesity in Canada was examined from the National Population Health Survey (1994-2001) and the Canadian Community Health Survey (2001-2011). The reductions in CRC incidence among Canadians are limited to older populations. While reductions among younger age groups (20-29year olds (yo), 30-39yo and 40-50yo) were observed between 1969 and 1995, rates have returned to and surpassed historical levels (APCs 20-29yo colon cancer=6.24%, APCs 20-29yo rectal cancer=1.5%). Recent birth cohorts (1970-1990) have the highest incidence rate ratios ever recorded. Ecologic trends in obesity prevalence among these birth cohorts in Canada are suggestive of an impact on increasing incidence trends. Furthermore, obesity prevalence estimates suggest that these trends may continue to increase justifying further examination of the etiologic associations and biological impacts of excess adipose tissue among younger populations. While population-based screening of younger age groups deserves careful consideration, these concerning observed trends warrant public health action to address the growing obesity epidemic.

Intake of dietary fibre and lifetime non-steroidal anti-inflammatory drug (NSAID) use and the incidence of colorectal polyps in a population screened for colorectal cancer

Background There is suggestive evidence that increased intake of dietary fibre and the use of non-steroidal anti-inflammatory drugs (NSAIDs) are generally associated with decreased colorectal cancer risk. However, the effects on precursors of colorectal cancer, such as adenomatous polyps, are mixed. We present the associations between dietary fibre intake and NSAID use on the presence and type of colorectal polyps in a screening population. Methods A cross-sectional study of 2548 individuals undergoing colonoscopy at the Forzani & MacPhail Colon Cancer Screening Centre (Calgary, Canada) was conducted. Dietary fibre intake and NSAID use were assessed using the Diet History Questionnaire I or II and the Health and Lifestyle Questionnaire. Colorectal outcomes were documented as a polyp or high-risk adenomatous polyp (HRAP; villous histology, high-grade dysplasia, ≥10 mm or ≥3 adenomas). Crude and ORs and 95% CIs were estimated using unconditional logistic regression. Results There were 1450 negative colonoscopies and 1098 patients with polyps, of which 189 patients had HRAPs. Total dietary fibre intake was associated with a decreased presence of HRAPs (OR=0.50, 95% CI: 0.29 to 0.86) when comparing the highest to lowest quartiles and was observed with both soluble (OR=0.51, 95% CI: 0.30 to 0.88) and insoluble (OR=0.51, 95% CI: 0.30 to 0.86) fibres. Ever use of NSAIDs was also inversely associated with HRAPs (OR=0.65, 95% CI: 0.47 to 0.89), observed with monthly (OR=0.60, 95% CI: 0.37 to 0.95) and daily (OR=0.53, 95% CI: 0.32 to 0.86) use. Conclusions Dietary fibre intake and NSAID use were associated with a decreased risk of having a HRAP at screening.

Impact of aerobic exercise on levels of IL-4 and IL-10: results from two randomized intervention trials.

The mechanisms whereby regular exercise reduces chronic inflammation remain unclear. We investigated whether regular aerobic exercise alters basal levels of interleukin (IL)‐10 and IL‐4 in two randomized trials of physical activity. The Alberta Physical Activity and Breast Cancer Prevention Trial (ALPHA, n = 320) and the Breast Cancer and Exercise Trial in Alberta (BETA, n = 400) were two‐center, two‐armed randomized trials in inactive, healthy, postmenopausal women. Both trials included an exercise intervention prescribed five times/week and no dietary changes. In ALPHA, the exercise group was prescribed 225 min/week versus no activity in the controls. BETA examined dose‐response effects comparing 300 (HIGH) versus 150 (MODERATE) min/week. Plasma concentrations of IL‐10 and IL‐4 were measured at baseline, 6, and 12 months. Intention‐to‐treat (ITT) analysis was performed using linear mixed models adjusted for baseline biomarker concentrations. Circulating anti‐inflammatory cytokine levels decreased among all groups, with percent change ranging from −3.4% (controls) to −8.2% (HIGH) for IL‐4 and −1.6% (controls) to −7.5% (HIGH) for IL‐10. No significant group differences were found for IL‐4 (ALPHA P = 0.54; BETA P = 0.32) or IL‐10 (ALPHA P = 0.84; BETA P = 0.68). Some evidence for moderation of the effect of exercise by baseline characteristics was found for IL‐10 but not for IL‐4. Results from these two large randomized aerobic exercise intervention trials suggest that aerobic exercise does not alter IL‐10 or IL‐4 in a manner consistent with chronic disease and cancer prevention.

The association between recreational physical activity, sedentary time, and colorectal polyps in a population screened for colorectal cancer

PURPOSE Regular recreational moderate to vigorous physical activity (rMVPA) has been previously associated with a reduced risk of colorectal cancer (CRC), however, few studies have examined the association of rMVPA with colorectal polyps, the pre-malignant precursor lesions. The objective of this study was to examine the associations between physical activity and sitting time and polyps at the time of screening. METHODS We conducted a cross-sectional study of 2496 individuals undergoing screening-related colonoscopy in Calgary, Alberta, Canada. Physical activity and sitting time were characterized using hours of rMVPA, meeting physical activity recommendations and hours of sitting time using self-reported data obtained from the International Physical Activity Questionnaire. Logistic regression models were used to estimate the crude and adjusted odds ratios (OR) for presence of polyps associated with rMVPA and sitting time. RESULTS Meeting physical activity guidelines of ≥150 min/week was non-significantly associated with a modest decrease in odds of having ≥1 polyp at screening (ORadj = 0.95, 95% CI: 0.80-1.14). In males, threshold effects for sitting time were observed for up to 20 h/week (ORadj per hour sitting = 1.07, 95% CI: 1.01-1.13). In stratified analysis, larger inverse associations were observed between physical activity and the presence of polyps in females, obese individuals, and ever smokers, compared to pooled findings. CONCLUSIONS In this large CRC screening population, there was a suggestive association between increased rMVPA and reduced prevalence of polyps at screening, particularly among females. Even low amounts of regular sitting time (0-20 h/day) were associated with the presence of polyps, particularly among males. Further research on rMVPA and sitting time is necessary to better inform strategies to reduce the frequency of pre-malignant colorectal lesions.

Effects of physical activity on colorectal cancer risk among family history and body mass index subgroups: a systematic review and meta-analysis

BackgroundPhysical 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.MethodsWe 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.ResultsThe 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).ConclusionsOverall, 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.

Abstract B02: Recreational physical activity, sedentary time and the incidence of colorectal polyps in a screening population for colon cancer

Background: Despite the consistent association between regular recreational moderate to vigorous physical activity (rMVPA) and reduced risk of colorectal cancer (CRC), few studies have examined the effect of physical activity on carcinogenic development by examining colorectal adenomas (polyps). Furthermore, even fewer studies have examined the impact of sedentary behavior/time (ST) on the development of polyps. In this study we examined the associations between rMVPA and ST and the presence, number and type of colorectal polyps in a population undergoing screening for colorectal cancer in Calgary, Alberta, Canada. Methods: A cross-sectional study of 2,499 individuals undergoing colonoscopy at the Forzani & MacPhail Colon Cancer Screening Centre in Calgary, Canada was conducted. Physical activity levels and ST were characterized using hours of rMVPA, meeting cancer prevention recommendations (≥150 mins/wk of rMVPA) and hours of ST using self-reported data from the Long Form International Physical Activity Questionnaire. Unconditional logistic regression models were used to estimate the crude and adjusted odds ratios (OR) for presence of polyps associated with rMVP and ST. Results: Crude estimates for meeting cancer prevention guidelines (ORunadj=0.83, 95% CI: 0.70-0.98) and increasing rMVPA (ORunadj=0.75, 95% CI: 0.60-0.93 for 1-3 hrs/wk vs. 0) were associated with lower odds of having ≥1 polyp at screening. Effect estimates were attenuated in adjusted models. Threshold effects were observed for ST with significant associations observed for up to 20 hours/week of sitting time (ORadj per hour sitting=1.05, 95% CI: 1.01-1.09). Associations were strongest for rMVPA among females (ORadj=0.68, 95% CI: 0.48-0.97 for 1-3 hrs/wk vs. 0) and for ST among males (ORadj=1.74, 95% CI: 1.06-2.86 for 14-35hrs/wk of ST vs. 0-14 hrs/wk) Conclusions: In this large population undergoing colonoscopy screening for colorectal cancer, rMVPA was associated with reduced prevalence of polyps at screening, particularly among females. Even low amounts of regular ST (2-5hrs/day) were associated with the presence of polyps, particularly among males. Strategies aimed at reducing the amount of pre-carcinogenic colon lesions should combine increasing rMVPA and reducing ST. Citation Format: Darren R. Brenner, Demetra H. Yannitsos, Matthew Warkentin, Eileen Shaw, Nigel T. Brockton, S. Elizabeth McGregor, Susanna Town, Robert J. Hilsden. Recreational physical activity, sedentary time and the incidence of colorectal polyps in a screening population for colon cancer. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr B02.