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Type: Thesis
Title: Defining the role of lipids and metabolic factors as risk factors for prostate cancer incidence and aggressiveness
Author: Aref, Adel Tahseen
Issue Date: 2019
School/Discipline: Adelaide Medical School
Abstract: Prostate Cancer (PCa) is the second most common cancer and among the top causes of cancer-related mortality among men. In recent years there has been a growing debate about the effect of metabolic factors (diabetes, hypertension, and hyperlipidaemia) and obesity on prostate cancer risk and aggressiveness. This thesis aims to uncover the role of metabolic factors, sex hormones, and obesity as risk factors for prostate cancer incidence and aggressiveness, and how the metabolic factors and sex hormones are important confounders in prostate cancer risk assessment and screening models. It also aims to review how assessing different aspects of obesity including peri-prostatic fat influences prostate cancer incidence and aggressiveness. The thesis consists of five chapters: • Chapter 1 is a literature review and it includes; * Section 1 an introduction to prostate cancer risk factors. * Section 2 a summary of prostate cancer as a metabolic disease. * Section 3 a summary of the debate around prostate cancer screening. * Section 4 a summary of the debate around the role of sex hormones in prostate cancer pathogenesis. * Section 5 (published review) a review on the role of periprostatic versus subcutaneous fat and its association with prostate cancer risk. • Chapter 2 (published research): describes the inverse relationship between obesity and PSA levels and the underlying mechanisms • Chapter 3 (research submitted for publication) describes how obesity attenuates prostate cancer screening and leads to an underestimation of prostate cancer risk. • Chapter 4 (research prepared for publication) describes how metabolic factors may attenuate prostate cancer screening efficacy. • Chapter 5 (research submitted for publication) describes the association between sex hormones and prostate cancer characteristics at the time of diagnosis. The research work done through this project and as part of this thesis, have shown that: • Obesity leads to lower PSA levels through two main mechanisms, first; the change in the sex hormone levels among men with obesity (mainly the increase in the estradiol-to-testosterone ratio), second; the increase in the plasma volume among men with obesity. • The lowers levels of PSA among men with obesity (especially moderate and severe obesity) could lead to underestimation of prostate cancer risk and potentially delay prostate cancer diagnosis. • Metabolically healthy men (those without diabetes, hypertension or obesity) appear to benefit from prostate cancer screening in terms of reducing their risk of prostate cancer-specific mortality, in comparison to those who have one or more of these conditions. • Sex hormones (mainly the higher estradiol-to-testosterone ratio) are associated with a higher Gleason score at the time of diagnosis. The results of this project give opportunities to introduce and identify new risk reduction modalities and interventions, as well as identify factors that may attenuate the efficacy of prostate cancer screening. The effect of these factors needs to be confirmed in randomised controlled trials. Longer term, applying the results of this project in clinical practice may refine the implementation and/or interpretation prostate cancer screening, and improve the available risk reduction interventions.
Advisor: Butler, Lisa
Vincent, Andrew
O'Callaghan, MIchael
Hoy, Andrew
Dissertation Note: Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 2019
Keywords: Prostate cancer
metabolic factors
prostate cancer screening
metabolic syndrome
sex hormones
Provenance: This electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at:
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