# Exercise as it relates to Disease/Exercise in the prevention of cancer
## Background
### Exercise

Exercise is considered an activity that enhances or maintains physical fitness and overall health [1]. It provides a pathway for both weight loss and maintenance, while strengthening bones, skeletal muscle and the cardiovascular system. Regular exercise provides boosts to the immune system, and helps prevent various dabilitating diseases such as heart disease, cardiovascualar disease, cancer, type 2 diabetes and obesity[1][2].

### Cancer

Cancer is a disease of the body's cells. Under normal circumstances cells grow and multiplay in a controlled way, however when mutations occur in a cell's replication process this control can be lost, leading to the formation of irregular cells. Cancer is the term used to describe collections of these mutated cells growing and possibly spreading within the body. As any type of tissue cell can become cancerous there are around 100 different diseases that fall under the category of cancer[2].

## Bowel Cancer

Exercise has been found to help waste pass through more quickly, reducing contact time with cancer-causing agents. [1]

## Exercise and Obesity prevention

The main mechanism behind exercises ability to prevent cancer lies in its weight maintenance and minimising properties. According to current WHO data taken in 2008, 1.4 billion adults over the age of 20 were overweight, and 500 million of these individuals were classed as obese – 11% of the total world population [3]. Obese individuals are considered high risk for the development of a multitude of diseases including, but not limited too, coronary heart disease, type 2 diabetes and cardiovascular diseases [4]. Research suggests cancers have been causally linked to obesity through processes that occur within the obese individual that increase the risk of their development [5-9]. It is believed that anywhere between 7 and 41% of reported presentation of cancers may be attributed to obesity [10].
The primary biological mechanisms linking obesity and cancer are believed to be altered endocrine secretion from adipose tissue, weight induced hyperinsulinaemia, an altered concentration and presentation of sex hormones, and inflammation and oxidative stress caused by inflammatory cytokines such as TNF-Alpha [5-9][11-14].

### Endocrine Secretion

Adiponectin is an anti-proliferative adipokine that has been shown to have a highly protective role against the spread of cancerous cell material due to its pro-apoptotic and anti-inflammatory qualities. However, while Adiponectin is a cytokine that is produced by adipose tissue, it is also inhibited by the presence of inflammatory cytokines. As large levels of adipose tissue become a collecting site for inflammatory cytokines such as TNF-Alpha and Interlukin-6, Adiponectin levels are presented in significantly reduced quantities in obese individuals, limiting their cancer preventing affects [7][8][9].

### Inflammation

Obese individuals often suffer chronic inflammation due to the collection of TNF-Alpha and Interlukin-6 that occurs between adipose tissue cells. This turns into a cycle as extended periods of inflammation will, in turn, produce abnormal quantities of inflammatory cytokines, further increasing the levels TNF-Alpha and IL-6 within the afflicted site. Cytokines initiate cell proliferation and angiogenesis, while inhibiting pro-apoptotic and anti-inflammatory compounds. Therefore, they can have a direct influence on the development and progression of specific forms of cancer. Chronic inflammation also produces reactive oxygen species, which outside their immune function, may have a detrimental effect on the body by damaging DNA and inducing changes within tissues that can lead to cancer development [11-14].

### Sex Hormones

Amongst the obese population the level of sex-hormone binding globulin available within plasma and tissues is significantly decreased. This in turn causes a significant increase in the number of sex steroids such as oestrogen and androgen found free floating in blood plasma. These sex steroids stimulate cell proliferation and inhibit apoptosis, providing a beneficial environment for tumor growth [8][9].
It has also been found that amongst previously sedentary postmenopausal women, those that begin to adhere to a moderate to vigorous-intensity exercise program underwent changes to estradiol and sex-hormone binding globulin concentrations. These changes have been found to lower the risk of postmenopausal breast cancer. This was found to be the case in both obese and non obese individuals, suggesting that exercise alone was the reason behind the changes [15].

### Hyperinsulinaemia and Tumour Growth

Hyperinsulinaemia and the overproduction of free plasma insulin-like growth factor-I are common symptoms in those suffering from obesity. Free plasma insulin and insulin-like growth factor-I have been shown to play a significant role in the carcinogenic process. Both insulin and IGF-I are anti-apoptotic compounds that stimulate cell proliferation and have been positively linked to the formation and growth of tumours. Exercise has been shown to decrease the body's production of insulin and IGF-I, providing both a preventative quality and a possible way to enhance treatment after the onset of tumor growth has occurred.[8][9]

## Recommendations

The cancer council of Australia recommends that "1 hour of moderate activity daily or 30 minutes of vigorous activity is recommended to cut your cancer risk". Moderate intensity activity is anything causing a slight but noticeable increase in breathing and heart rate while vigorous activity makes you 'huff and puff', and is defined as exercise at 70% to 85% of your maximum heart rate. These recommendations are for already healthy individuals, and those classified as obese should undertake measures to lower their body fat percentages in order to minimize their risk of cancer [2][4].

## References

[1] Oxford Dictionary Online [Online]. Definition of Exercise. http://www.oxforddictionaries.com/definition/english/exercise
[2] Cancer Council Australia [Online]. Cancer Council Australia. http://www.cancer.org.au/
[3] World Health Organisation [Online] “Obesity and Overweight: Fact sheet No. 311”. WHO c2013. Available from: http://www.who.int/mediacentre/factsheets/fs311/en/
[4] Department of Health and Ageing [Online] “Promoting Healthy Weight: About Overweight and Obesity”. Commonwealth of Australia c2013. Distributed by Australian Government Department of Health and Ageing. Available from: http://www.health.gov.au/internet/main/publishing.nsf/content/health-pubhlth-strateg-hlthwt-obesity.htm#consequences
[5] Ceshi, M., Gutzwiller, F., Mocj, H., Eichholzer, M., Probst-Hensch, N.M. Epidemiology and pathophysiology of obesity as cause of cancer. Swiss Med. Wkly. 2007. 137(3-4): 50-56. Available from: http://www.smw.ch/docs/pdf200x/2007/03/smw-11435.PDF
[6] Pischon, T., Nothlings, U., Boeing, H. Obesity and cancer. Proc. Nutr. Soc. 2008. 67(2): 128-145. Available from: http://journals.cambridge.org/action/displayFulltext?type=6&fid=1842816&jid=PNS&volumeId=67&issueId=02&aid=1842812&bodyId=&membershipNumber=&societyETOCSession=&fulltextType=RA&fileId=S0029665108006976
[7] Van Kruijsdijk, R.C., Van Der Wall, E., Visseren F.L. Obesity and Cancer: The Role of Dysfunctional Adipose Tissue. Cancer Epidemiol. Biomarkers Prev. 2009. 18(10): 2569-2578. Available from: http://cebp.aacrjournals.org/content/18/10/2569.full.pdf+html
[8] Roberts, D.L., Dive, C., Renehan, A.G. Biological mechanisms linking obesity and cancer risk: new perspectives. Annu. Rev. Med. 2010. 61: 301-316. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19824817
[9] Renehan, A.G., Roberts, D.L., Dive, C. Obesity and cancer: Pathophysiological and biological mechanisms. Arch. Physiol. Biochem. 2008. 114(1): 71-83. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18465361
[10] International Association for the Study of Obesity [Online] “Estimating the association between overweight and risk of disease”. IASO c2013. Available from: http://www.iaso.org/policy/healthimpactobesity/
[11] Naugler, W.E., Karin, M. The wolf in sheep's clothing: the role of interleukin-6 in immunity, inflammation and cancer. Trends Mol. Med. 2008. 14(3): 109-119. Available from: http://molpath.ucsd.edu/PDF/Naugler,Karin-2008%5B1%5D.pdf
[12] Grivennikov, S.I., Greten, F.R., Karin, M. Immunity, Inflammation, and Cancer. Cell. 2010. 140(6): 883-899. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866629/
[13] Park, E.J., Lee, J.H., Yu, G.Y., He, G., Ali, S.Y., Holzer, R.G., et al. Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell. 2010. 140(2): 197-208. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2836922/
[14] Naugler, W.E., Karin, M. The wolf in sheep's clothing: the role of interleukin-6 in immunity, inflammation and cancer. Trends Mol. Med. 2008. 14(3): 109-119. Available from: http://molpath.ucsd.edu/PDF/Naugler,Karin-2008%5B1%5D.pdf
[15] Morimoto, L.M., White, E., Chen, Z., Chlebowski, R.T., Hays, J., Kuller, L., et al. Obesity, body size, and the risk of postmenopausal breast cancer: the Women's Health Initiative (United States). Cancer Causes Control. 2002. 13(8): 741-751. Available from: http://link.springer.com/article/10.1023/A%3A1020239211145