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      Exercise-induced biochemical changes and their potential influence on cancer: a scientific review

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          Abstract

          Aim

          To review and discuss the available international literature regarding the indirect and direct biochemical mechanisms that occur after exercise, which could positively, or negatively, influence oncogenic pathways.

          Methods

          The PubMed, MEDLINE, Embase and Cochrane libraries were searched for papers up to July 2016 addressing biochemical changes after exercise with a particular reference to cancer. The three authors independently assessed their appropriateness for inclusion in this review based on their scientific quality and relevance.

          Results

          168 papers were selected and categorised into indirect and direct biochemical pathways. The indirect effects included changes in vitamin D, weight reduction, sunlight exposure and improved mood. The direct effects included insulin-like growth factor, epigenetic effects on gene expression and DNA repair, vasoactive intestinal peptide, oxidative stress and antioxidant pathways, heat shock proteins, testosterone, irisin, immunity, chronic inflammation and prostaglandins, energy metabolism and insulin resistance.

          Summary

          Exercise is one of several lifestyle factors known to lower the risk of developing cancer and is associated with lower relapse rates and better survival. This review highlights the numerous biochemical processes, which explain these potential anticancer benefits.

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          Physical activity, biomarkers, and disease outcomes in cancer survivors: a systematic review.

          R Ballard-Barbash, C Friedenreich, K S Courneya … (2012)
          Cancer survivors often seek information about how lifestyle factors, such as physical activity, may influence their prognosis. We systematically reviewed studies that examined relationships between physical activity and mortality (cancer-specific and all-cause) and/or cancer biomarkers. We identified 45 articles published from January 1950 to August 2011 through MEDLINE database searches that were related to physical activity, cancer survival, and biomarkers potentially relevant to cancer survival. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement to guide this review. Study characteristics, mortality outcomes, and biomarker-relevant and subgroup results were abstracted for each article that met the inclusion criteria (ie, research articles that included participants with a cancer diagnosis, mortality outcomes, and an assessment of physical activity). There was consistent evidence from 27 observational studies that physical activity is associated with reduced all-cause, breast cancer-specific, and colon cancer-specific mortality. There is currently insufficient evidence regarding the association between physical activity and mortality for survivors of other cancers. Randomized controlled trials of exercise that included biomarker endpoints suggest that exercise may result in beneficial changes in the circulating level of insulin, insulin-related pathways, inflammation, and, possibly, immunity; however, the evidence is still preliminary. Future research directions identified include the need for more observational studies on additional types of cancer with larger sample sizes; the need to examine whether the association between physical activity and mortality varies by tumor, clinical, or risk factor characteristics; and the need for research on the biological mechanisms involved in the association between physical activity and survival after a cancer diagnosis. Future randomized controlled trials of exercise with biomarker and cancer-specific disease endpoints, such as recurrence, new primary cancers, and cancer-specific mortality in cancer survivors, are warranted.
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            Effects of Exercise Training on Cardiorespiratory Fitness and Biomarkers of Cardiometabolic Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

            Xiaochen Lin, Xi Zhang, Jianjun Guo … (2015)
            Background Guidelines recommend exercise for cardiovascular health, although evidence from trials linking exercise to cardiovascular health through intermediate biomarkers remains inconsistent. We performed a meta-analysis of randomized controlled trials to quantify the impact of exercise on cardiorespiratory fitness and a variety of conventional and novel cardiometabolic biomarkers in adults without cardiovascular disease. Methods and Results Two researchers selected 160 randomized controlled trials (7487 participants) based on literature searches of Medline, Embase, and Cochrane Central (January 1965 to March 2014). Data were extracted using a standardized protocol. A random-effects meta-analysis and systematic review was conducted to evaluate the effects of exercise interventions on cardiorespiratory fitness and circulating biomarkers. Exercise significantly raised absolute and relative cardiorespiratory fitness. Lipid profiles were improved in exercise groups, with lower levels of triglycerides and higher levels of high-density lipoprotein cholesterol and apolipoprotein A1. Lower levels of fasting insulin, homeostatic model assessment–insulin resistance, and glycosylated hemoglobin A1c were found in exercise groups. Compared with controls, exercise groups had higher levels of interleukin-18 and lower levels of leptin, fibrinogen, and angiotensin II. In addition, we found that the exercise effects were modified by age, sex, and health status such that people aged <50 years, men, and people with type 2 diabetes, hypertension, dyslipidemia, or metabolic syndrome appeared to benefit more. Conclusions This meta-analysis showed that exercise significantly improved cardiorespiratory fitness and some cardiometabolic biomarkers. The effects of exercise were modified by age, sex, and health status. Findings from this study have significant implications for future design of targeted lifestyle interventions.
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              Diabetes mellitus and risk of breast cancer: a meta-analysis.

              Susanna C Larsson, Christos S. Mantzoros, Alicja Wolk (2007)
              Diabetes mellitus has been associated with an increased risk of several types of cancers, but its relationship with breast cancer remains unclear. We conducted a meta-analysis of case-control and cohort studies to assess the evidence regarding the association between diabetes and risk of breast cancer. Studies were identified by searching MEDLINE (1966-February 2007) and the references of retrieved articles. We identified 20 studies (5 case-control and 15 cohort studies) that reported relative risk (RR) estimates (odds ratio, rate ratio/hazard ratio, or standardized incidence ratio) with 95% confidence intervals (CIs) for the relation between diabetes (largely Type II diabetes) and breast cancer incidence. Summary RRs were calculated using a random-effects model. Analysis of all 20 studies showed that women with (versus without) diabetes had a statistically significant 20% increased risk of breast cancer (RR, 1.20; 95% CI, 1.12-1.28). The summary estimates were similar for case-control studies (RR, 1.18; 95% CI, 1.05-1.32) and cohort studies (RR, 1.20; 95% CI, 1.11-1.30). Meta-analysis of 5 cohort studies on diabetes and mortality from breast cancer yielded a summary RR of 1.24 (95% CI, 0.95-1.62) for women with (versus without) diabetes. Findings from this meta-analysis indicate that diabetes is associated with an increased risk of breast cancer.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Br J Sports Med
                Journal ID (iso-abbrev): Br J Sports Med
                Journal ID (hwp): bjsports
                Journal ID (publisher-id): bjsm
                Title: British Journal of Sports Medicine
                Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                ISSN (Print): 0306-3674
                ISSN (Electronic): 1473-0480
                Publication date (Print): April 2017
                Publication date (Electronic): 19 December 2016
                Volume: 51
                Issue: 8
                Pages: 640-644
                Affiliations
                [1 ]Primrose Oncology Unit, Bedford Hospital NHS Trust , Bedford, UK
                [2 ]Department of Urology, University of California , San Francisco, California, USA
                [3 ]Centre for Applied Biological and Exercise Sciences, Faculty of Health and Life Sciences, Coventry University , Coventry, UK
                Author notes
                [Correspondence to ] Professor Robert James Thomas, Primrose Oncology Unit, Bedford Hospital NHS Trust, Kempston Road, Bedford MK42 9DJ UK; rt@ 123456cancernet.co.uk
                Article
                Publisher ID: bjsports-2016-096343
                DOI: 10.1136/bjsports-2016-096343
                PMC ID: 5466928
                PubMed ID: 27993842
                SO-VID: d3483617-ecb2-42d7-969e-04b16fa7cd4d
                Copyright © Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
                License:

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

                History
                Date accepted : 19 November 2016
                Categories
                Subject: 1506
                Subject: 1767
                Subject: Review
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                ScienceOpen disciplines: Sports medicine
                Keywords: exercise,biochemistry,cancer,evidence based review
                Data availability:
                ScienceOpen disciplines: Sports medicine
                Keywords: exercise, biochemistry, cancer, evidence based review

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