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Title: Analysis of the incidence and patient survival for prostate cancer in the West of Scotland
Author: Shafique, Kashif
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2012
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Prostate cancer has emerged as the most frequently diagnosed cancer, except for non-melanoma skin cancer, among men in many Western countries in the last decade. In the United Kingdom (UK), prostate cancer accounts for nearly a quarter of all new male cancer diagnoses. Increasing age and some genetic and ethnic risk factors have been identified but few modifiable risk factors are known. The introduction of Prostate Specific Antigen (PSA) testing has increased the detection of previously undiagnosed disease but its contribution to the observed increases in prostate cancer incidence is not clear. Considerable variations in the incidence of prostate cancer have been observed in different geographic regions and socio-economic groups across the UK but it is not known whether, or to what extent, these may be attributed to differential uptakes of PSA testing. Prostate cancer is the third most common cause of cancer death in men but many cases do not progress. There is therefore an important clinical need for better prognostic markers so that the increasing numbers of men with prostate cancer can be appropriately managed. This thesis begins with a descriptive epidemiological study using cancer registry incidence data from the West of Scotland from 1991 to 2007. The aim was to determine whether the incidence of prostate cancer was continuing to rise and to describe any demographic or socio-economic patterns that might suggest particular at-risk groups. To understand whether any socio-economic differentials in incidence might be due to PSA testing, I examined Gleason grade-specific prostate cancer incidence by socio-economic groups over time. Socio-economic circumstances were measured using census-derived Carstairs scores. Overall (age adjusted) prostate cancer incidence increased by 70% from 44 per 100,000 in 1991 to 75 per 100,000 in 2007, an average annual growth of 3.59%. This pattern was driven by significant increases in both low and high grade cancers with no convincing change in their proportions over time. Incidence was inversely associated with deprivation with the highest rates among the most affluent groups. To explore the role of potentially modifiable risk factors on prostate cancer incidence, the Midspan and Collaborative prospective cohort studies were analysed. An analysis of the relationship between cholesterol and prostate cancer incidence was conducted on the Midspan cohort, which comprises 12,926 men who were enrolled between 1970 and 1976 and followed up to 31st December 2007. Cox Proportional Hazards Models were used to evaluate the association between baseline plasma cholesterol and Gleason grade-specific prostate cancer incidence. Following up to 37 years’ follow-up, 650 men developed prostate cancer. Their baseline plasma cholesterol level was positively associated with hazard of high grade (Gleason score ≥8) prostate cancer incidence (n=119). The association was greatest among men in the 4th highest quintile for cholesterol, 6.1 to <6.69 mmol/l, Hazard Ratio 2.28, 95% CI 1.27 to 4.10, compared with the baseline of <5.05 mmol/l. This association remained significant after adjustment for age, body mass index, smoking and socio-economic status. Evidence on the possible role of tea and coffee consumption in the development of prostate cancer remains limited to a small number of studies with short follow-up and small numbers of cases. Therefore to understand the relationship of tea and coffee consumption with overall as well as grade-specific prostate cancer, a prospective cohort study of 6016 men was carried out, who were enrolled in the Collaborative cohort study between 1970 and 1973 and followed up to 31st December 2007. Three hundred and eighteen men developed prostate cancer in up to 37 years’ follow-up. I found a positive association between consumption of tea and overall risk of prostate cancer incidence (p=0.02). The association was greatest among men who drank ≥7 cups of tea per day (HR 1.50, 95% CI 1.06 to 2.12) compared with the baseline of 0-3 cups per day. However, I did not find any significant association between tea intake and low (Gleason < 7) or high grade (Gleason 8-10) prostate cancer incidence. Higher coffee consumption was inversely associated with risk of high grade disease (HR 0.46, 95% CI 0.21-0.99) but not with overall risk of prostate cancer. These associations remained significant after adjustment for age, Body Mass Index, smoking, social class, cholesterol level, systolic blood pressure and alcohol consumption. Although survival of prostate cancer patients has improved over time, little is known about the major prognostic factors. To understand the socio-economic differences and major determinants of survival, an investigation was carried out using cancer registry incidence data from the West of Scotland from 1991 to 2007, linked with General Registrar Office (Scotland) death records up to 31st December 2008. Socio-economic circumstances were measured using the Scottish Index for Multiple Deprivation (SIMD). Age, sex and deprivation specific mortality rates were obtained from General Registrar Office for Scotland (GRO(S)). One, three and five year relative survival was estimated using the complete approach. Survival gradients across deprivation quintiles were estimated using linear regression, weighted by the variance of the relative survival estimate, using STATA software (StataCorp, version 11). Five year relative survival increased from 58.2% to 78.6% in men over the same period (an average deprivation adjusted increase of 10.2% between six years periods). Despite substantial improvements in survival of prostate cancer patients, there was a deprivation gap (that is, better survival for the least deprived compared with the most deprived) between the three time periods. The deprivation gap in five year relative survival widened from -4.76 in 1991-1996 to -10.08 in 2003-2007. Age, Gleason grade and socio-economic status appeared as significant determinants of survival. There is some evidence that systemic inflammation may be associated with survival in patients with prostate cancer although its relationship to tumour grade and socio-economic circumstances has not been previously studied. I therefore investigated the association between inflammation-based prognostic scores and survival, using the modified Glasgow Prognostic Score (mGPS) and Neutrophil Lymphocyte Ratio (NLR) as well as Gleason grade. The patient cohort within the Glasgow Inflammation Outcome Study who had a diagnosis of prostate cancer was included in this study. The mGPS is a categorical score constructed by combining serum C-reactive protein and albumin levels, while the NLR is obtained by calculating the ratio of neutrophils to lymphocytes. The relationship between mGPS and NLR and five-year relative survival was explored after adjusting for age, socio-economic circumstances and Gleason grade. Of the 897 prostate cancer patients in the Glasgow Inflammation Outcome Study, 422 (47%) died during a maximum follow-up of 6.2 years. Systemic inflammation had a significant prognostic value. The mGPS predicted poorer 5-year overall and relative survival independent of age, socio-economic circumstances, disease grade and NLR. Raised mGPS also had a significant association with excess risk of death (mGPS 2: Relative Excess Risk = 2.08, 95% CI 1.13-3.81) among aggressive, clinically significant prostate cancer (Gleason score 8-10). Prostate cancer patients with a raised mGPS had significantly higher risks of death overall as well as for high grade disease. Inflammation-based prognostic scores can potentially predict patient outcome and a further prospective study is warranted to assess their clinical value.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RC0254 Neoplasms. Tumors. Oncology (including Cancer) ; RA0421 Public health. Hygiene. Preventive Medicine