Darren R. Brenner

Leisure-time physical activity and lung cancer risk: A systematic review and meta-analysis

OBJECTIVES We conducted a systematic review and meta-analysis of the association between recreational physical activity and lung cancer risk to update previous analyses and to examine population subgroups of interest defined by smoking status and histology. MATERIALS AND METHODS We searched the PubMed database for studies up to May 2015. Individual study characteristics were abstracted including study design, number of cases, assessment of recreational physical activity and type and level of adjustment for confounding factors. Combined effect estimates were calculated for the overall associations and across subgroups of interest. RESULTS We identified 28 studies that were eligible for inclusion in the meta-analysis. The overall analysis indicated an inverse association between recreational physical activity and lung cancer risk (Relative Risk (RR), 0.76; 95% Confidence Interval (CI), 0.69-0.85, p-value: <0.001). Similar inverse associations with risk were also noted for all evaluated histological subtypes, including adenocarcinoma (RR, 0.80; 95% CI, 0.72-0.88), squamous (RR, 0.80; 95% CI, 0.71-0.90) and small cell (RR, 0.79; 95% CI, 0.66-0.94). When we examined effects by smoking status, inverse associations between recreational physical activity and lung cancer risk were observed among former (RR, 0.77; 95% CI, 0.69-0.85) and current smokers (RR, 0.77; 95% CI, 0.72-0.83), but not among never smokers (RR, 0.96; 95% CI, 0.79-1.18). CONCLUSION Results from this meta-analysis suggest that regular recreational physical activity may be associated with reduced risk of lung cancer. Only four studies examining never smokers were identified, suggesting the need for additional research in this population.

The Association between Leisure Time Physical Activity and Pancreatic Cancer Risk in Adults: A Systematic Review and Meta-analysis

We conducted a meta-analysis of the association between leisure time physical activity (LTPA) and risk of pancreatic cancer to update previous analyses in light of newly published studies, to examine subgroups of interest and potential sources of heterogeneity. We searched the PubMed and MEDLINE databases for studies until February 2015. Study information was collected using a standardized form to abstract relevant data on study design, number of cases, participant and study characteristics, assessment of LTPA, risk estimates, and adjustments for confounding by two independent abstractors. We used random-effects models to pool estimates from included studies of lowest versus highest comparison of LTPA. The search identified 26 studies eligible for inclusion into the meta-analysis. The combined summary risk estimate was [relative risk (RR), 0.89; 95% confidence interval (CI), 0.82–0.96]. There was evidence of heterogeneity across studies (I2 = 22.1%, Pheterogeneity = 0.130). Some of the heterogeneity could be explained by study design, with stronger protective effects observed among case–control studies (RR, 0.69; 95% CI, 0.59–0.81) compared with cohort studies (RR, 0.96; 95% CI, 0.91–1.02). Across study designs, age of population was a source of heterogeneity, with stronger effects observed among younger (<50 years) populations. The present meta-analysis supports a protective association between LTPA and pancreatic cancer with an 11% risk reduction observed. LTPA appears to have the strongest effect among young populations. Additional investigations are needed to provide insights regarding the impact of LTPA in healthy adult populations, to reduce the risk of pancreatic cancer and encourage increases in LTPA. Cancer Epidemiol Biomarkers Prev; 24(10); 1462–73. ©2015 AACR.

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.

A Systematic Review of the Effect of Lifestyle Interventions on Adipose Tissue Gene Expression: Implications for Carcinogenesis

The mechanisms driving the associations between body weight and physical activity levels and multiple types of cancer are not yet well understood. The purpose of this review was to examine the effects of lifestyle interventions on proposed biomarkers of lifestyle and cancer risk at the level of adipose tissue in humans.

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.

A Review of Physical Activity and Circulating miRNA Expression: Implications in Cancer Risk and Progression

The role of circulating miRNAs (c-miRNAs) in carcinogenesis has garnered considerable scientific interest. miRNAs may contribute actively to cancer development and progression, making them potential targets for cancer prevention and therapy. Lifestyle factors such as physical activity (PA) have been shown to alter c-miRNA expression, but the subsequent impact on cancer risk and prognosis is unknown. To provide a better understanding of how PA reduces the risk of cancer incidence and improves patient outcomes, we conducted a review of the impact of PA on c-miRNA expression, which includes a comprehensive synthesis of studies examining the impacts of acute and chronic exercise on expression of c-miRNAs. While the variability in methods used to assess miRNA expression creates challenges in comparing and/or synthesizing the literature, results to date suggest that the circulating form of several miRNAs known for playing a role in cancer (c-miR-133, c-miR-221/222, c-miR-126, and c-let-7) are altered by both acute and chronic PA. Additional research should develop standardized procedures for assessing both c-miRNA and PA measurement to improve the comparability of research results regarding the direction and amplitude of changes in c-miRNAs in response to PA. Cancer Epidemiol Biomarkers Prev; 27(1); 11–24. ©2017 AACR.

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.

Effect of a 12-month exercise intervention on leukocyte telomere length: Results from the ALPHA Trial

BACKGROUND Short telomeres may indicate a higher risk of cancer and other chronic diseases. Some observational studies show positive associations between leukocyte telomere length (LTL) and physical activity levels. We hypothesized, therefore, that exercise may be one strategy for slowing telomere attrition. METHODS We conducted an ancillary analysis of blood from a year-long, two-centred, two-armed (1:1) randomized controlled trial of aerobic exercise versus usual inactivity. The analysis included 212 physically inactive, disease-free, non-smoking, postmenopausal women (n = 99 exercisers, n = 113 controls) in Alberta, Canada (2003-2006). The exercise prescription was aerobic exercise five days/week (supervised three days/week), 45 min/session, achieving 70-80% heart rate reserve. Baseline and 12-month LTL were analyzed using quantitative real-time polymerase chain reactions (qPCR). The primary statistical analysis was intention-to-treat, comparing the ratio of mean LTLs (12-months:baseline) for exercisers versus controls from a general linear model. Secondary analyses included a per-protocol analysis (≥90% adherence) and analyses stratified by baseline LTL, age, body mass index, and fitness level, respectively. RESULTS Participants were overweight at baseline (mean BMI = 29 kg/m2). The primary analysis showed no evidence that LTL change differed between groups (12-month mean LTL change for the exercise group: -13% (95% CI: -32%, 11%) versus controls: -8% (95%CI: -27%, 15%); treatment effect ratio (TER, Exercise/Control) = 0.95 (95% CI: 0.68, 1.32). Per-protocol results were similar (TER = 0.87, 95% CI: 0.59, 1.30). In stratified models, TERs ranged from 0.68 to 1.35 across strata and P-interaction > 0.05). CONCLUSION We found no evidence to suggest that one year of aerobic exercise alters telomere attrition significantly in healthy postmenopausal women.

Physical activity does not alter prolactin levels in post-menopausal women: results from a dose-response randomized controlled trial

BackgroundIncreased 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.MethodsFour 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.ResultsA 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).ConclusionsIt 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 registrationclinicaltrials.gov identifier: NCT01435005.