Causes And Preventions Of Cancer Biology Essay

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According to the latest statistics from the World Health Organisation, cancer causes around 7.6 million deaths worldwide each year. Changes in lifestyle and improved prevention and screening policies could prevent up to 40% of all cancer cases (WHO 2010). Physical inactivity has been identified as the 4th leading risk factor for global mortality. It is estimated to be the main cause for approximately 21-25% of breast and colorectal cancer (WHO 2009). Several biological mechanisms have been proposed to explain how a reduction adipose tissue by physical activity may protect against various cancers (Friedenreich 2010). This review, will analysis these mechanisms in relation to physical activity and their role in reducing breast and colorectal cancer risk.

Physical activity is any bodily movement produced by skeletal muscles; such movement results in an expenditure of energy (NIH 2009). It is typically quantified, for example, as h/week of activity or as metabolic equivalents (MET) h/week, where MET is estimated intensity of an activity (McTiernan 2008). Physical activity activates mechanisms, which results in changes in body composition, insulin resistance, sex hormones, adipokines, inflammation, immune function and has a possible effect on vitamin D (Friedenreich 2010). The diagram below depicts a reduction in adipose tissue, by physical activity, which lowers the production of sex hormones, insulin, leptin and inflammatory biomarkers. The cancer risk is reduced by decreasing the exposure to these carcinogenic hormones (McTiernan 2008).

Figure 1: Hypothesized mechanisms linking physical activity to cancer risk or prognosis.

Of the possible mechanisms associated with physical activity and cancer prevention, weight control plays a significant role (Friedenreich et al 2010). It was not till 2002 that the International Agency for cancer research stated that excess body weight is an avoidable cause of colorectal cancer in men and postmenopausal breast cancer in women (IARC 2002). A higher BMI has been consistently associated with the risk of colon cancer (Giovannucci 2001). Similarly obesity is a well established risk of postmenopausal breast cancer (Van den Brandt et al 2000). The evidence that physical activity is a protective factor for colon cancer is strong and remarkably consistent (Friedenreich 2001). Chronic excess energy intake causes obesity, which is the strongest determinant of insulin resistance and hyperinsulinemia (Renehan et al 2006).

Insulin resistance describes the reduced effectiveness of insulin to regulate blood glucose, primarily via skeletal muscle (Perez-Martin 2001). Thereby resulting in hyperglycaemia, hyperinsulinemia and elevated biomarkers including C-peptides. It is strongly related to obesity and central adiposity (Haslam and James 2005). Rizzo et al (2008) conducted The European Youth Heart Study on 613 adolescents and concluded that increased time spent at vigorous physical activity had an inverse effect on insulin resistance and body fat in obese adolescents. A dose-response effect was observed with greater decreases in body fat occurring with higher doses of exercise per week. However (Frank et al 2005) stated that physical activity can result in reduced insulin resistance even without changes in body composition. The insulin-cancer hypothesis proposes a central role for elevated levels of bio-active IGF-I (insulin growth factor) in the development and progression of cancerous tumours. Likewise Kaaks and Lukanova (2001) states, that insulin resistance has been linked to an increased risk of breast and colon cancer. The Physicians Study analysed 14,916 cancer free men over a 13-year period those with C-peptide in the top versus the bottom quintile had a 2.7 fold significantly higher risk of colorectal cancer when compared to the control group (Ma et al 2004).

A further consequence of adipose tissue is the production of adipokines they include leptin and adiponectin (Guyton and Hall 2006). They are considered common indicators of inflammation. (Rajala and Scherer 2003) Chronic inflammation has been an acknowledged risk factor for several cancers, as it can deregulate normal cell growth and promote specific cells towards malignancy (Li and Karin 2007). Regular physical activity works through the mechanism of reducing inflammation by decreasing adipocytokines production in the body. F or instance, in a study conducted by (Frank et al 2005) which analysed the effects of physical activity on 173 obese postmenopausal women over a 12 month period. It was found that the group who participated in >45 minutes of moderately-intensity aerobic activity MET had a 7% decrease in leptin compared to the control group who only did stretching exercises their leptin levels remained the same. Similarly excess leptin production, due to obesity has been associated with increased production of available sex hormones endogenous estrogens. This potentially initiates and promotes breast cancer in postmenopausal women (Key et al 2006; Garofalo et al 2007). A randomised study conducted by (McTiernan et al 2004) over a 12-month trial found that postmenopausal women who decreased body fat through physical activity had significantly decreased oestrogens and androgens production compared to those who did not lose body weight.

Similarly it is apparent that obesity causes negative alterations in immune function by decreasing killer cells (Neiman et al 1999). It is suggested that physical activity works through the mechanism to reduce cancer by increasing the number and function of the natural killer cells (Jakobisiak et al 2003).

In relation to colorectal cancer, the mechanism by which physical activity may decrease bowl transit time, and thus reduce exposure of colonic moucosa to mutagens and carcinogens in faeces. However, changes are probably of insufficient magniture to alter risk significantly. (Harriss 2009)

Breast cancer:

Peel et al (2009) observed in analysis of 14,811 women aged between 20-83 years, that high cardiorespiratory fitness (CRF) demonstrated a 55% lower risk of dying of breast cancer compared to the women in the low CRF group. Similarly a review by Monninkhof et al (2007) found evidence of an extreme inverse association between vigorous physical activity and breast cancer in postmenopausal women. A 20-80% decrease risk of incident disease was observed. In contrast George et al (2010) noted that beyond recreational physical activity: everyday occupational, household and active commuting may protect against invasive but not in situ breast cancer. The study analysed 97, 039 women with no pervious cancer history and concluded women who reported engaging in manual work had a 38% risk reduction for those who reported sedentary work. This worked through mechanisms to lower BMI, estrogen and insulin resistance all factors associated with physical activity and cancer risk (Neilson et al 2009).

Physical activity reduces breast cancer risk when performed at any age through-out life, but it has a more beneficial effect affect above the age of 50 compared to younger ages (Friedenreich and Cust 2008). The Nurses’ Health Study included 2,987 women with stage 1-3 stage breast cancer, they were followed for a median 96 months. It concluded that physical activity preformed was shown to be beneficial in women with all stages of disease, but was particularly beneficial in women diagnosed with higher stages of cancer (Martinez et al 1997).

Current public health recommendations for breast cancer risk reduction are for at least 4-7h per week of moderate to vigorous-intenity activity. (PAG 2008; Friedenreich 2010)

Colon cancer:

A higher body mass index has been consistently associated with risk of colon cancer (Friedenreich 2001). This is evident in a study by European Prospective Investigation into Cancer and Nutrition (EPIC), which was based on 984 cases of colon cancer. A 55% increase risk of cancer was observed between the high and lower quartiles of BMI in men but not in women (Pischon et al 2006). However it was noted that postmenopausal women with a higher BMI were correlated with higher estrogen levels, which may have a competing beneficial effect on colon cancer (Giovannucci 2001). Likewise 120,147 females were analysed over a six year period in The California Teachers Study. They had no previous colon cancer history. Moderate and strenuous exercise had a 25% risk reduction among women who at least exercised 4h/wk/y. Physical activity was strongly associated with colon cancer risk in postmenopausal women who had not previously used hormone therapy. (Mai et al 2007)

Nurses’ Health Study 6 year follow up showed that leisure inversely associated with colon cancer. Compared with women with an energy expenditure level <2MET per week, women with the highest level of metabolic energy expenditure >21MET hours per week had a 46% reduction in risk of colon cancer (Martinez et al 1997) However this is

Qualitive assessment in 2004 you need intensive exercise to reduce cancer risk however (Lee 2006) moderate intensity exercise may be sufficient of colon cancer. 30-60 mins of moderate to vigorous-intensity physical activity may be needed to lower colon cancer risk. (Kushi 2006)

The above review adds further evidence of the beneficial role physical activity plays in the prevention of breast and colorectal cancer. It is one of most critical components to alter weight gain and obesity. However further studies are required into the discussed mechanisms, to identify duration, intensity and frequency to achieve an anti-carcinogenic effect, also the standardization of these exercise related. On reflection the main message obtained from this assignment was “Prevention is a more effective strategy than is treatment of chronic diseases” (Lui RH, 2003)

Physical activity and physical fitness been shown to be beneficial to cancer patients. (Courneya 2003)

Likewise physical activity could be associated with higher 25-hydroxyvitamin D blood levels due to a decrease in adipose tissue thus reducing risk of colon and breast cancer even thought this mechanism is unclear (Harriss et al 2009).