BackgroundHigh cholesterol may be a modifiable risk factor for prostate cancer but results have been inconsistent and subject to potential "reverse causality" where undetected disease modifies cholesterol prior to diagnosis.MethodsWe conducted a prospective cohort study of 12,926 men who were enrolled in the Midspan studies between 1970 and 1976 and followed up to 31st December 2007. We used Cox-Proportional Hazards Models to evaluate the association between baseline plasma cholesterol and Gleason grade-specific prostate cancer incidence. We excluded cancers detected within at least 5 years of cholesterol assay.Results650 men developed prostate cancer in up to 37 years' follow-up. Baseline plasma cholesterol was positively associated with hazard of high grade (Gleason score≥8) prostate cancer incidence (n = 119). The association was greatest among men in the 2nd 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 body mass index, smoking and socioeconomic status.ConclusionsMen with higher cholesterol are at greater risk of developing high-grade prostate cancer but not overall risk of prostate cancer. Interventions to minimise metabolic risk factors may have a role in reducing incidence of aggressive prostate cancer.

BACKGROUND: There is some evidence that systemic inflammation may be associated with survival in patients with prostate cancer; however, it is unclear whether this is independent of grade. We therefore investigated the role of inflammation-based prognostic scores, the modified Glasgow Prognostic Score (mGPS) and neutrophil lymphocyte ratio (NLR), and their associations with Gleason grade in patients with prostate cancer. METHODS:Patients from a cohort, the Glasgow Inflammation Outcome Study, who had diagnosis of prostate cancer, were included in this study. The mGPS was constructed by combining C-reactive protein and albumin whereas NLR by calculating the ratio of neutrophils to lymphocytes. We estimated 5-year relative survival and relative excess risk (RER) of death by mGPS and NLR categories after adjusting for age, socioeconomic circumstances and Gleason grade. RESULTS:In all, 897 prostate cancer patients were identified; of those 422 (47%) died during a maximum follow-up of 6.2 years. Systemic inflammation appeared to have significant prognostic value. The mGPS predicted poorer 5-year overall and relative survival independent of age, socioeconomic circumstances, disease grade and NLR. Raised mGPS also had a significant association with excess risk of death (mGPS 2: RER ¼ 2.41, 95% confidence interval 1.37-4.23) among aggressive, clinically significant prostate cancer (Gleason grades 8-10). CONCLUSIONS:The mGPS is a strong measure of systemic inflammation, when compared with NLR. Prostate cancer patients with a raised mGPS had significantly higher risk of death for overall as well high-grade disease. Inflammationbased prognostic scores predict outcome in patients with prostate cancer and should be added to their routine clinical assessment.

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Summary The matrix metalloproteinases are a family of enzymes that degrade the extracellular matrix and are considered to be important in tumour invasion and metastasis. The effect of epidermal growth factor (EGF) on matrix metalloproteinase-1 (MMP1) production in two human bladder tumour cell lines, RT112 and RT4, has been investigated. In the RT112 cell line, an increase in MMP1 mRNA levels was found after a 6-h incubation with EGF, and this further increased to 20-fold that of control levels at 24-and 48-h treatment with 50 ng ml-1 of EGF. MMP2 mRNA levels remained constant over this time period, whereas in the RT4 cells no MMP2 transcripts were detectable, but MMP1 transcripts again increased with 24-and 48-h treatment with 50 ng ml-' of EGF. MMP1 protein concentration in the conditioned medium from both cell lines increased with 24-and 48-h treatment of the cells and the total MMP1 was higher in the medium than the cells, demonstrating that the bladder tumour cell lines synthesize and secrete MMP1 protein after continuous stimulation with EGF. MMP1 protein was detected in urine from patients with bladder tumours, with a significant increase in concentration with increased stage and grade of tumour. MMP1 urine concentrations may therefore be a useful prognostic indicator for bladder tumour progression.Keywords: matrix metalloproteinase-1; epidermal growth factor; bladder tumour; urine; RT1 12 cells; RT4 cellsThe matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that contain a zinc atom at their active site. They are found in both normal and pathological tissue in which matrix remodelling is involved, including embryonic development, wound healing, arthritis and angiogenesis, as well as tumour invasion and metastasis (Matrisian, 1990;Liotta et al, 1991). The enzymes, which are cytoplasmic or membrane type , are secreted in a latent (pro) form and require activation by removal of approximately 80 amino acids from the propeptide, and other metalloproteinases and proteases are involved in this activation (Powell and Matrisian, 1996;Stetler-Stevenson et al, 1996). Additional regulation of the enzymes is by endogenous tissue inhibitors of metalloproteinases (TIMPS), of which four have now been identified (Greene et al, 1996). These proteins form a stable non-covalent complex with the enzymes, inhibiting their activity. Various members of the MMP family and their inhibitors have been studied to elucidate their role in cancer, in which deregulation of their expression and function has been implicated in the invasion of normal tissues by tumours and their subsequent metastatic spread. Invasive tumour progression is particularly evident in bladder cancer, in which it is a central feature of the prognostic staging system. Bladder cancer is the fifth most common cancer in men, and transitional cell carcinoma (TCC) of the bladder can be broadly divided into superficial (Ta and T1) or muscle invasive (T2, T3 and T4) forms. Approximately 50-70% of superficial tumours recur, but 10-20% will become invasiv...

BackgroundHigher consumption of coffee intake has recently been linked with reduced risk of aggressive prostate cancer (PC) incidence, although meta-analysis of other studies that examine the association between coffee consumption and overall PC risk remains inconclusive. Only one recent study investigated the association between coffee intake and grade-specific incidence of PC, further evidence is required to understand the aetiology of aggressive PCs. Therefore, we conducted a prospective study to examine the relationship between coffee intake and overall as well as grade-specific PC risk.MethodsWe conducted a prospective cohort study of 6017 men who were enrolled in the Collaborative cohort study in the UK between 1970 and 1973 and followed up to 31st December 2007. Cox Proportional Hazards Models were used to evaluate the association between coffee consumption and overall, as well as Gleason grade-specific, PC incidence.ResultsHigher coffee consumption was inversely associated with risk of high grade but not with overall risk of PC. Men consuming 3 or more cups of coffee per day experienced 55% lower risk of high Gleason grade disease compared with non-coffee drinkers in analysis adjusted for age and social class (HR 0.45, 95% CI 0.23-0.90, p value for trend 0.01). This association changed a little after additional adjustment for Body Mass Index, smoking, cholesterol level, systolic blood pressure, tea intake and alcohol consumption.ConclusionCoffee consumption reduces the risk of aggressive PC but not the overall risk.