Robinson, Fredie
(2012)
Prostate cancer risk factors: a UK population based case-control study centered on chronic diseases, medications, sunlight and diet.
PhD thesis, University of Nottingham.
Abstract
Background: Prostate cancer risk has been associated with several environmental factors but there is little information to indicate the effects of timing and of lifetime exposures that may add to the risk. This thesis aims to investigate the association of six main areas that may contribute to prostate cancer risk (1) body shape & fat distribution, (2) chronic diseases/conditions (diabetes mellitus, hypertension, ischaemic heart diseases and hypercholesterolemia), (3) statin medications (4) painkillers (NSAIDs and paracetamol), (5) skin & sunlight exposure and (6)diet (isoflavones, selenium, vitamin D & lycopene). The exposures will be investigated at different stages of life for subsequent effects on cumulative prostate cancer risk.
Methodology: This study is a part of "The UK Prostate Cancer Study: Gene-Environment Interactions", which is an ongoing large scale case-control study and a collaboration between the University of Nottingham, University of Warwick and the Institute of Cancer Research UK. Data were collected using questionnaires. Subjects were recruited between the years of 1999 to 2009 as cases and controls from hospitals and GPs' referrals in England. Possible risk factors for prostate cancer are investigated through statistical analyses using unconditional logistic regression to obtain odds ratios (OR) and confidence intervals.
Results: The response rate was 85.0% among cases and 74.4% among controls, with a total of 4041 males (1963 cases and 2078 controls) recruited into the study. The mean age among cases and controls was 59.6 and 59.1 years respectively. Multivariate analysis of socio-demographic factors showed education, ethnic group and family history were statistical significantly associated with prostate cancer risk and therefore are treated as confounders. Further, (1) Body fat distribution of 'apple' and 'oval' shapes were found to have protective effect towards prostate cancer when compared with a symmetrical shape with an OR of 0.69 (95% CI: 0.55- 0.87) and 0.73 (95% CI 0.53-1.00) respectively, however body shape at age 20's, 30's, 40's and last 5 years showed no statistical difference between cases and controls. (2) The cumulative duration of diabetes mellitus categorised as 5 years or more and 10 years or more when compared to non-diabetic individuals had a protective effect towards prostate cancer risk at OR 0.45 (95%CI: 0.27-0.75) and 0.44 (95% CI: 0.22-0.86) respectively while hypertension, hypercholesterolemia and ischaemic heart disease did not associate with prostate cancer risk. (3) Use of Statins for less than 5 years compared to non-users, produced an OR 0.61 (95%CI: 0.47-0.82). A dose response relationship for duration of use was also seen. (4) Paracetamol showed a protective effect for prostate cancer risk when used for 20 years to 30 years when compared to none-users, OR 0.54 (95%C1: 0.28-1.00). Similarly paracetamol showed a cumulative risk reduction against prostate cancer for all categories of use of up to 20 years or more. However aspirin and ibuprofen did not show any statistical significant associations with prostate cancer risk. (5) Higher exposure to sunlight received in non-working situations and more frequent use of suntan cream showed protective effects against prostate cancer and also when accounted for exposure at different stages of life age. (6)Dietary isoflavones and tablet supplements of selenium at higher intake quartiles levels showed a protection effect against prostate cancer risk when compared to lowest quartile intake.
New surrogate indicators for body size and sunlight exposure and a proposed model for overall vitamin D levels from sunlight and dietary sources were also introduced.
Conclusions: Body fat distribution of 'apple' and 'oval' body forms, diabetes mellitus, statin usage, higher exposure to sunlight and higher dietary intakes of isoflavones were shown to associate with a decreased risk for prostate cancer. The findings of this case-control study strengthen and support the current understanding of environmental factors associated with prostate cancer risk, whilst at the same time provides further evidence on the effects of exposure at different stages in life and their cumulative effect, as well identifying new surrogate indicators as parameters measurement for such exposures.
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