Prostate cancer risk and recurrence: the role of nutrition and clinical aspects

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 toobtain 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.