1. PROSTATE CANCER AND SMOKING Kym Hickey MBBS, MPH Repatriation Medical Authority, Australia

2. 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)

3. Learning Objectives Be aware of data concerning prostate cancer and smoking Understand epidemiological criteria used to assess causality

4. Performance Objectives How to assess new evidence on prostate cancer & smoking How to apply epidemiological criteria to other questions of causality

5. 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

6. Identification of Studies Medline search Review of bibliographies of identified studies Conference papers

7. Assessment of Study Quality Study design / selection issues Measurement of prostate cancer & smoking Control of confounding Statistical issues

8. 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

9. 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

10. 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

11. StudyNo. CasesRR, CI 15541.3, 0.61-2.79 161660.76, 0.51-1.14 172431.1, 1.0-1.3

12. 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

13. 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

14. 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

15. Hospital-based Case-Control 12 out of 16 hospital-based case-control studies found no association between current or ever smoking and prostate cancer

16. Methodological Criticisms I ? Differential measurement of prostate cancer in mortality cohorts ? Differential screening of prostate cancer in mortality cohorts

17. Methodological Criticisms II ? Confounding by dietary fat ? Differential treatment of prostate cancer by smoking status

18. 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)

19. Causal Criteria – Strength of Association Association observed between current smoking and fatal prostate cancer was weak – about a 30% increase in risk

20. 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

21. 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 ?

22. 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

23. Causal Criteria – Biological Plausibility Various mechanisms proposed – cadmium, male hormones, genetic mutations, immune dysfunction – but none clearly established

24. 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 ??

25. 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)

26. 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