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Prostate Cancer Risk and Recurrence the Role of Nutrition and Clinical Aspects

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Prostate Cancer Risk and Recurrence the Role of Nutrition and Clinical Aspects Prostate cancer risk and recurrence the role of nutrition and clinical aspects Dieuwertje E.G. Kok Thesis committee Promoters Prof. dr. ir. E. Kampman Personal chair at the Division of Human Nutrition Wageningen University Prof. dr. L.A.L.M. Kiemeney Professor of Cancer Epidemiology Radboud University Medical Centre, Nijmegen Co-promoter Dr. ir. L.A. Afman Assistant professor, Division of Human Nutrition Wageningen University Other members Prof. dr. R.J.A. van Moorselaar VU University Medical Center Amsterdam Dr. B.A.J. Verhage Maastricht University Dr. ir. W.M. van Weerden Erasmus MC, Rotterdam Prof. dr. ir. F.J. Kok Wageningen University This research was conducted under the auspices of the Graduate School VLAG (Advanced studies in Food Technology, Agrobiotechnology, Nutrition and Health Sciences) Prostate cancer risk and recurrence the role of nutrition and clinical aspects Dieuwertje E.G. Kok Thesis submitted in fulfilment of the requirements for the degree of doctor at Wageningen University by the authority of the Rector Magnificus Prof. dr. M.J. Kropff, in the presence of the Thesis Committee appointed by the Academic Board to be defended in public on Tuesday 29 January 2013 at 11.00 a.m. in the Aula. Dieuwertje E.G. Kok Prostate cancer risk and recurrence: the role of nutrition and clinical aspects, 172 pages PhD thesis, Wageningen University, Wageningen, the Netherlands (2013) With references, with summary in Dutch ISBN 978-94-6173-301-6 Abstract Background Prostate cancer is the most common cancer among men in Western countries. Knowledge on prostate cancer aetiology is required for identification of high-risk groups, optimization of treatment strategies, and development of prevention programs. The aim of this thesis was to obtain insight into nutritional and clinical factors relevant to different stages of prostate cancer. Methods and results First, an inventory of potential risk factors for prostate cancer was made by asking 956 patients with prostate cancer about perceived causes of their disease. Among the 143 patients who provided self-reported causes, heredity, specific environmental factors, nutrition or lifestyle, and stress were most frequently reported. Second, two potential risk factors, i.e. blood lipid levels and a previous cancer diagnosis, for incident prostate cancer were evaluated. Higher levels of total and LDL cholesterol were significantly associated with an increased risk of (aggressive) prostate cancer after 6.5 years of follow-up in a population-based cohort of 2,118 men (43 cases). Analyses from another population-based cohort among 551,553 men (9,243 cases) showed that cancer survivors diagnosed with a first cancer (other than prostate cancer) between 1989 and 2008 had an overall increased risk of prostate cancer in the first year after their first cancer diagnosis. This increased prostate cancer risk is most likely the result of active screening or incidental detection, because the effects disappeared after one year of follow-up for most of the specific first cancer sites. Third, the effect of body mass index (BMI) on risk of biochemical recurrence was studied in two cohorts of 493 patients (142 cases) and 1,302 patients (297 cases) treated with radical prostatectomy for prostate cancer. BMI was not associated with risk of biochemical recurrence in these patients. Finally, the effects of selenium, a suggested candidate for prostate cancer chemoprevention, on gene expression profiles in the prostate were examined in a randomized and placebo-controlled intervention trial with 15 participants (n=8 selenium, n=7 placebo). Selenium (300 µg/day as selenized yeast) affected the expression of genes towards an anti-inflammatory gene expression profile. Furthermore, we were able to detect expression changes in genes implicated in the epithelial-to-mesenchymal transition. Conclusion The results of this thesis show that specific nutritional and clinical factors might influence risk of prostate cancer or have an effect on gene expression in the prostate. A future challenge is the confirmation and 'translation' of these findings into the development and implementation of effective treatment and prevention strategies for prostate cancer. Contents Chapter 1 Introduction 9 1.1 General introduction to prostate cancer 10 1.2 Risk factors and prevention of prostate cancer 16 1.3 Risk factors and prevention of prostate cancer progression 21 1.4 Risk factors and prevention of prostate cancer recurrence 23 1.5 Overview of this thesis 25 Chapter 2 Why I got prostate cancer: an explorative study on 35 perceived causes of prostate cancer Chapter 3 Blood lipid levels and prostate cancer risk: a cohort study 49 Chapter 4 Risk of prostate cancer among cancer survivors in the Netherlands 61 Chapter 5a Body mass index is not a predictor of biochemical recurrence 73 after radical prostatectomy in Dutch men diagnosed with prostate cancer Chapter 5b Body mass index as a prognostic marker for biochemical 85 recurrence in Dutch men treated with radical prostatectomy Chapter 6 Selenium affects expression of genes implicated in inflammation 95 and epithelial-to-mesenchymal transition in the prostate Chapter 7 Discussion 121 7.1 Outline 123 7.2 Implications for researchers 123 7.3 Implications for (future) patients 141 7.4 Implications for the urologist 144 7.5 Future research agenda 146 Samenvatting (Summary in Dutch) 153 Dankwoord (Acknowledgements) 159 About the author 165 Introduction The overall aim of this thesis is to obtain insight into nutritional and clinical aspects relevant to different stages of prostate cancer. In the following paragraphs, an introduction to prostate cancer will be provided. Basic aspects of the epidemiology, pathology, carcinogenesis, diagnosis, and treatment of prostate cancer will be discussed in light of the topics addressed in this thesis (paragraph 1.1). Furthermore, an overview of potential risk factors and targets for prevention of incident (paragraph 1.2), progressive (paragraph 1.3) and recurrent (paragraph 1.4) prostate cancer will be presented. As this thesis covers a relatively broad and extensive research area, some of the aspects discussed in this chapter will not be specifically addressed in the following chapters. Instead, this information can be used as background information and might be useful for the interpretation or discussion of the study outcomes. This chapter ends with the specific research aims and the outline of this thesis. | Chapter 1 1.1 General introduction to prostate cancer The incidence of prostate cancer Prostate cancer is the most common cancer among men in Western countries1, 2. It is estimated that almost one out of ten Dutch men will develop prostate cancer before the age of 803, 4. With 21%, prostate cancer accounted for the majority of all newly diagnosed cancers in Dutch men in 20094. In the Netherlands, 10,166 men were newly diagnosed with prostate cancer in 2009, while 2,492 men died from this disease in the same year4. Prostate cancer is predominantly diagnosed in elderly men. In 2009, 70% of all newly diagnosed Dutch prostate cancer patients were men aged 65 years and older4. Diagnosis There are no characteristic symptoms for prostate cancer, because most of the reported local symptoms, such as lower urinary tract symptoms (LUTS), refer to benign prostatic disorders more specifically. The detection and diagnosis of prostate cancer is often based on serum levels of the prostate-specific antigen (PSA) and a digital rectal examination, followed by ultrasound-guided prostate biopsies. Several prostate cancer-specific biomarkers in urine, blood and tissue have been evaluated, but so far none of these biomarkers is widely used in clinical practice5. In contrast to few other cancers (i.e. cervical cancer and breast cancer in females), there is no national screening program for prostate cancer in the Netherlands. The controversy about such screening program refers to the lack of cancer specificity of PSA testing6. Furthermore, it has been determined that the benefits are not likely to balance the possible harms (i.e. complications of treatment and mental burden7) of early screening8-10. Pathology and staging Normal prostate tissue consists of glandular tissue surrounded by non-glandular components (e.g. fibromuscular stroma)11. The prostate ducts are lined by two layers of epithelial cells, with neuroendocrine cells dispersed throughout these layers12. The secretory luminal cells directly line the lumen of the prostate ducts, while the basal cells form the second layer of epithelial cells12. The vast majority of the cancers in the prostate arises from the epithelial cells and are therefore defined as prostatic adenocarcinomas13. Within the prostate, three morphological zones can be distinguished; the peripheral zone, the transition zone, and the central zone11, 14. The majority of all prostatic adenocarcinomas (~70%) occur in the peripheral zone, which is also highly susceptible to inflammation, while 20-25% and 5-10% arise from the Page| 10 Introduction| transition zone and central zone, respectively11, 15, 16. Benign prostate enlargement (benign prostate hyperplasia or BPH) typically originates from the transition zone17. Histological grading is a tool for pathologists to assess the architecture of a tumour. The Gleason grading system for prostatic adenocarcinomas is grouped into five categories18. Gleason grade 1 refers to well-differentiated tumours (resemble normal prostate tissue), whereas poorly-differentiated tumours (abnormal architecture) are
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