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Prostate cancer is the second most common cancer among men across the world and the most common in many countries. Evidence from ecological studies points towards important environmental causes and dietary factors have been implicated.
However, despite a huge amount of research, very few modifiable risk factors have been established, although body fatness and height seem to explain some of the risk, particularly for advanced disease. In a recent World Cancer Research Fund International systematic review update the conclusions for many nutritional factors were actually downgraded, due to inconsistencies between studies and possibly also due to the heterogeneous nature of prostate cancer.
Systematic reviews are acknowledged as the most rigorous way to synthesise data which have addressed a common question. In collaboration with World Cancer Research Fund International we have developed guidelines for identifying mechanistic pathways between exposures and disease and systematically reviewing the literature which supports these mechanistic pathways, including judging the quality and reproducibility of these studies.
Hypothesis and objectives
There are two main objectives of this project; the first is to use Mendelian randomization to determine the unconfounded risk of nutritional factors on prostate cancer risk in localised and advanced prostate cancer.
We hypothesise that low levels of vitamin D, selenium, lycopene and vitamin E and high levels of iron, folate and vitamin B12 lead to a decreased risk of prostate cancer and in particular advanced cancer. The second is to use a set of guidelines which we have developed in collaboration with World Cancer Research Fund International to carry out rigorous systematic reviews of mechanistic studies of body fatness, and vitamin D levels and advanced prostate cancer risk, to determine the likely mechanisms by which these factors are leading to advanced disease and to inform potential prevention strategies.
Settings and methods
This study will be based in the School of Social and Community Medicine at the University of Bristol (one of the UK’s leading centres for research and teaching in population health sciences). We will make use of a large consortium with genetic data on 65,000 prostate cancer cases and controls.
We will identify common genetic variants, which are associated with the nutrients of interest and develop genetic scores as proxy’s for nutritional exposure. We will then examine the association between these proxys and prostate cancer risk.
We will also carry-out a systematic review to summarise the evidence from mechanistic studies underlying the associations between body fatness and vitamin D and advanced prostate cancer. We will further test intermediates of the mechanistic pathway, highlighted in the review, using a Mendelian randomisation framework.
This will be the largest study of its kind in prostate cancer and will give a definitive insight into which, if any, of the nutrients we are examining cause prostate cancer. It will help us to understand how body size and vitamin D levels may influence prostate cancer progression.
The work will establish the basis for the development of food or nutrient trials in the future, and will inform public health messages aimed at reducing the burden of prostate cancer.