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Title: Prostate cancer biomarkers : adiposity, adipokines and lifestyle factors
Author: Burton , Anya J. G.
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2012
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Prostate cancer is a common cancer, particularly in Western countries. Increasing body mass index (BMI) has been associated with a modest increased risk of advanced and fatal prostate cancer (12-15% per 5 kg/m2 increase in BMI). Adipokines (adipose derived hormones) have been proposed as mediators of this association, but the results of several (mostly small) observational studies have been conflicting. The thesis describes investigations conducted into associations of adiposity, adipokines and lifestyle factors with prostate cancer; firstly, a systematic review and dose-response meta-analysis of the association of the adipokines adiponectin and leptin with prostate cancer incidence and progression. Secondly, a nested case-control study in men aged 50-69 with PSA-detected prostate cancer recruited during the case-finding stage of ProtecT (a population-based randomised trial of treatments for localised prostate cancer) compared BMI, WHR, adiponectin, leptin and leptin:adiponectin (L:A) ratio between 311 men with advanced (the cases) and 413 men with localised (the controls) prostate cancer. Finally, an exploration of associations of BMI, lifestyle factors and adipokines with age-related PSA change (,PSA growth') in men with localised prostate cancer undergoing active monitoring in ProtecT. The meta-analysis found adiponectin levels to be associated with a small reduced risk of total (OR 0.96, 95%CI 0.94-0.98, per 2.5~g/m1) and aggressive (OR 0.89, 95%CI 0.83-0.95) prostate cancer. The ProtecT case-control study indicated an inverse association of adiponectin with risk of advanced stage prostate cancer in overweight and obese men (p for interaction by BMI - 0.006; OR 0.62, 95% Cl 0.42- 0.90 per log(~g/ ml) in men ~25kg/m2}. The meta-analysis did not find a clear association between leptin and total (OR 1.01, 95% Cl 0.98-1.03 per 2.5 ng/ml) or aggressive (OR 1.01, 95%CT 0.99-1.06) prostate cancer and the ProtecT case-control study found little evidence of an association of leptin with prostate cancer stage or grade. There was weak evidence that L:A ratio was inversely associated with stage in normal weight men (OR 0.69, 95%CI 0.45-1.04) and positively associated with stage in overweight men (OR 1.22, 95%CI 0.97-1 .54) (p for interaction = 0.009). BMI was not associated with risk of advanced stage or high grade prostate cancer, or PSA growth, in ProtecT. In men undergoing active monitoring in ProtecT, exercise was inversely, and smoking was positively, associated with PSA at age 50 and yearly PSA growth; both of these factors have been linked to risk of aggressive or fatal prostate cancer. In conclusion, adiponectin appears protective against aggressive prostate cancer, particularly in overweight and obese men. Leptin and adiponectin (or L:A ratio) alone are unlikely to be major risk factors for overall prostate cancer and therefore their measurement at diagnosis would not aid prognostication. However, modification of adipokine levels through diet, exercise and weight loss is not likely to be harmful and may reduce the risk of other obesity-related cancers and diseases (e.g. cardiovascular disease). It is also unlikely that leptin is mediating the association of BMI with advanced or aggressive prostate cancer.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available