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PROSTATE CANCER AND SMOKING Kym Hickey MBBS, MPH Repatriation Medical Authority, Australia
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Prostate Cancer and Smoking Master’s thesis on this topic Review article on prostate cancer and smoking (Hickey et al 2001, Epidemiologic Reviews 23(1): 115-125)
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Learning Objectives Be aware of data concerning prostate cancer and smoking Understand epidemiological criteria used to assess causality
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Performance Objectives How to assess new evidence on prostate cancer & smoking How to apply epidemiological criteria to other questions of causality
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Why Prostate Cancer & Smoking Role of smoking in prostate cancer unclear Important public health issue as both smoking and prostate cancer are prevalent in community
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Identification of Studies Medline search Review of bibliographies of identified studies Conference papers
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Assessment of Study Quality Study design / selection issues Measurement of prostate cancer & smoking Control of confounding Statistical issues
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Results 65 controlled studies reported results for pc & smoking Results for both current & past smoking varied from protective for pc to increasing the risk of pc
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StudyNo. casesRR, CI 113691.04, 0.85-1.27 2690.56, 0.36-0.83 3712.2, 1.2-4.4 41800.49, 0.16-1.57 52381.46, 1.07-1.94 61981.0, 0.6-1.6 77071.1, 0.9-1.3
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StudyNo. CasesRR, CI 81740.87, 0.61-1.23 92201.08, 0.90-1.30 102,3681.11, 1.01-1.23 112091.11, 0.90-1.36 121090.82, 0.57-1.14 131380.9, 0.40-1.73 144061.00, 0.71-1.39
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StudyNo. CasesRR, CI 15541.3, 0.61-2.79 161660.76, 0.51-1.14 172431.1, 1.0-1.3
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StudyNo. CasesRR, CI 11031.58, 0.81-3.10 27091.26, 1.06-1.50 317481.34, 1.16-1.56 41341.75, 1.37-2.19 51471.1, 0.7-1.5 646071.18, 1.09-1.28 75690.99, 0.87-1.34
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StudyNo. CasesRR, CI 81492.0, 1.1-3.7 9321.83, 1.01-3.05 108261.31, 1.13-1.52 113191.02, 0.81-1.28 121930.93, 0.72-1.18 13301.38, 0.67-2.85
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Population-based Case-Control 10 out of 15 p-b case-control studies found no association between current or ever smoking & pc as did 4 out of 5 case-control studies that used hospital cases and population controls
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Hospital-based Case-Control 12 out of 16 hospital-based case-control studies found no association between current or ever smoking and prostate cancer
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Methodological Criticisms I ? Differential measurement of prostate cancer in mortality cohorts ? Differential screening of prostate cancer in mortality cohorts
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Methodological Criticisms II ? Confounding by dietary fat ? Differential treatment of prostate cancer by smoking status
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Causal Criteria - Consistency There was inconsistency between the results of the mortality cohorts (positive association between pc and current smoking) and incidence cohorts (no association)
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Causal Criteria – Strength of Association Association observed between current smoking and fatal prostate cancer was weak – about a 30% increase in risk
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Causal Criteria – Dose Response 2 cohorts found a D-R relation between current smoking and risk of incident pc 2 cohorts found a D-R relation between current or recent smoking and risk of fatal pc
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Prostate Cancer More Aggressive in Smokers ? Does the increased risk of advanced incident or fatal pc in recent or current smokers mean that pc follows a more aggressive course in smokers compared to nonsmokers ?
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Causal Criteria – Biological Plausibility Few studies on the effects of smoking on prostate cancer in animals Nitrosamines and pc in rats, tobacco smoke and pc tumor cell fraction in rats
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Causal Criteria – Biological Plausibility Various mechanisms proposed – cadmium, male hormones, genetic mutations, immune dysfunction – but none clearly established
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Male Hormones Probably most widely discussed of the proposed mechanisms Rests on two assumptions: smoking is anti-estrogenic and male sex hormones increase risk of prostate cancer but ??
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Male Hormones No diff. in mean serum level of T, free T, dihydroT, estrone, estradiol, androstenedione, DHEAS, between pc cases and controls in meta-analysis of 10 prospective studies (Eaton et al 1999 Br J Cancer 80: 930-4)
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Conclusion Positive association observed between smoking and fatal prostate cancer could be due to a methodological bias or prostate cancer may be more aggressive in smokers
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