The Effect of Exercise on Cancer Risk Factors in Males with Barrett's Oesophagus

Brooke Maree Winzer (2011). The Effect of Exercise on Cancer Risk Factors in Males with Barrett's Oesophagus PhD Thesis, School of Medicine, The University of Queensland.

       
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Author Brooke Maree Winzer
Thesis Title The Effect of Exercise on Cancer Risk Factors in Males with Barrett's Oesophagus
School, Centre or Institute School of Medicine
Institution The University of Queensland
Publication date 2011-12
Thesis type PhD Thesis
Supervisor Dr Jennifer Paratz
A/Prof David Whiteman
Dr Marina Reeves
Total pages 225
Total colour pages 17
Total black and white pages 208
Language eng
Subjects 110307 Gastroenterology and Hepatology
110699 Human Movement and Sports Science not elsewhere classified
111299 Oncology and Carcinogenesis not elsewhere classified
Abstract/Summary The incidence of oesophageal adenocarcinoma is rising faster than any other cancer. Overweight and obese males are at a particularly high risk of this cancer, especially those with the pre-malignant lesion, Barrett's oesophagus. If Barrett's oesophagus does progress to adenocarcinoma, prognosis is poor with a 5 year survival rate of 10-15%. At present there is a lack of evidenced-based interventions aimed at reducing oesophageal cancer risk in persons with Barrett's oesophagus. Oesophageal adenocarcinoma and Barrett's oesophagus have strong links with gastro-oesophageal reflux disease, overall body fatness and more specifically, abdominal obesity. Mechanisms mediating the positive relationship between adiposity and oesophageal adenocarcinoma may include the exacerbation of gastro-oesophageal reflux disease through mechanical factors, however metabolic mechanisms related to obesity may also be involved including altered concentrations of a number of obesity-related hormones. Exercise may be beneficial for those with Barrett's oesophagus due to its effects on reducing adiposity and improving levels of some obesity-related hormones; and possibly via reducing gastro-oesophageal reflux. Therefore exercise may be a suitable and feasible lifestyle treatment to lower oesophageal adenocarcinoma risk. However no trials have been conducted to date in adults with Barrett's oesophagus to evaluate the effect of exercise on mechanisms or "biomarkers" implicated in oesophageal adenocarcinoma development. The overall aim of this thesis is therefore to further understand the capacity of exercise to modulate oesophageal adenocarcinoma risk. To address this aim, two studies were undertaken: a systematic literature review and a randomised controlled trial. A systematic literature review was conducted to appraise previous trials evaluating the effect of exercise interventions on candidate biomarkers associated with cancer development. Findings of the review were used to inform the development of an exercise trial in persons with Barrett's oesophagus. A randomised controlled trial of exercise versus stretching was conducted in inactive males with Barrett's oesophagus (n = 33), aged 18 to 70 years, who were overweight or obese (body mass index 25.0 - 34.9 kg/m2). Participants were randomised to receive either a 24-week, moderate-intensity aerobic and resistance exercise intervention (60 min, 5 sessions/week) or stretching (45 min, 5 sessions/week). Outcomes were measured at baseline, 12-weeks and 24-weeks and included body composition (bio-impedance spectroscopy), abdominal adiposity (waist circumference), gastro-oesophageal reflux symptoms (Gastro-oesophageal Reflux Disease Impact Scale) and circulating concentrations of leptin, adiponectin (total, high molecular weight), C-reactive protein, interleukin-6, tumour necrosis factor-alpha, insulin and glucose. Insulin resistance was determined using homeostasis model assessment (HOMA) score. An intention-to-treat analysis was conducted as the primary analysis using generalised linear models. In addition, per-protocol and dose-response analyses were performed as an exploratory exercise. In total, 32 men (97%) completed the study. Men in the intervention group exercised an average of 4.2 hours/week. Compared to the control group, the exercise group recorded larger improvements in fitness and strength following 12- and 24-weeks of intervention, indicating good levels of adherence. From baseline to 24-weeks, reductions in waist circumference were greater in the exercise group compared with the control group (adjusted intervention effect -4.5 [95% CI -7.5, -1.4] cm; p < 0.01). Reductions in fat mass were also greater in the exercise group than the control group however the difference was non-significant (adjusted intervention effect -1.7 [95% CI -4.9, 1.7] kg; p = 0.32). Compared with controls, the exercise group recorded greater reductions in leptin levels (adjusted intervention effect -3.0 [95% CI -6.4, 0.5] ng/mL; p = 0.09). Changes in gastro-oesophageal reflux symptoms, C-reactive protein, interleukin-6, tumour necrosis factor-a and adiponectin levels did not differ between the groups, however levels of C-reactive protein, insulin and total adiponectin significantly decreased within both groups (p < 0.05). This novel and exploratory exercise trial found beneficial changes in a number of candidate biomarkers associated with oesophageal adenocarcinoma risk in males with Barrett's oesophagus including abdominal obesity, fat mass, leptin, insulin and insulin resistance. These findings, along with those from previous exercise trials in populations with a number of risk factors for breast and colon cancer, suggest that exercise can modulate various metabolic and hormonal pathways implicated in cancer development.
Keyword Exercise
Barrett's Oesophagus
Oesophageal adenocarcinoma
Cancer prevention
Biomarkers
Obesity
Adipokines
Insulin
Inflammatory Markers
Randomised controlled trial
Additional Notes Pages printed in colour: 24, 25, 69, 78, 79, 80, 81, 89, 90, 149, 151, 178, 179, 180, 181, 182, 183. Landscape pages: 36, 39, 41, 91, 93, 94, 205, 206, 207, 218, 219, 221, 222, 223.

 
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Created: Mon, 18 Jun 2012, 22:04:00 EST by Brooke Winzer on behalf of Library - Information Access Service