PROSTATE CANCER AND SMOKING

Kym Hickey MBBS, MPH

Repatriation Medical Authority, Australia

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)

Learning Objectives

• Be aware of data concerning prostate cancer and smoking

• Understand epidemiological criteria used to assess causality

Performance Objectives

• How to assess new evidence on prostate cancer & smoking

• How to apply epidemiological criteria to other questions of causality

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

Identification of Studies

• Medline search

• Review of bibliographies of identified studies

• Conference papers

Assessment of Study Quality

• Study design / selection issues

• Measurement of prostate cancer & smoking

• Control of confounding

• Statistical issues

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

Study No. cases RR, CI

1 1369 1.04, 0.85-1.27

2 69 0.56, 0.36-0.83

3 71 2.2, 1.2-4.4

4 180 0.49, 0.16-1.57

5 238 1.46, 1.07-1.94

6 198 1.0, 0.6-1.6

7 707 1.1, 0.9-1.3

Study No. Cases RR, CI

8 174 0.87, 0.61-1.23

9 220 1.08, 0.90-1.30

10 2,368 1.11, 1.01-1.23

11 209 1.11, 0.90-1.36

12 109 0.82, 0.57-1.14

13 138 0.9, 0.40-1.73

14 406 1.00, 0.71-1.39

Study No. Cases RR, CI

15 54 1.3, 0.61-2.79

16 166 0.76, 0.51-1.14

17 243 1.1, 1.0-1.3

Study No. Cases RR, CI

1 103 1.58, 0.81-3.10

2 709 1.26, 1.06-1.50

3 1748 1.34, 1.16-1.56

4 134 1.75, 1.37-2.19

5 147 1.1, 0.7-1.5

6 4607 1.18, 1.09-1.28

7 569 0.99, 0.87-1.34

Study No. Cases RR, CI

8 149 2.0, 1.1-3.7

9 32 1.83, 1.01-3.05

10 826 1.31, 1.13-1.52

11 319 1.02, 0.81-1.28

12 193 0.93, 0.72-1.18

13 30 1.38, 0.67-2.85

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

Hospital-based Case-Control

• 12 out of 16 hospital-based case-control studies found no association between current or ever smoking and prostate cancer

Methodological Criticisms I

• ? Differential measurement of prostate cancer in mortality cohorts

• ? Differential screening of prostate cancer in mortality cohorts

Methodological Criticisms II

• ? Confounding by dietary fat

• ? Differential treatment of prostate cancer by smoking status

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)

Causal Criteria – Strength of Association

• Association observed between current smoking and fatal prostate cancer was weak – about a 30% increase in risk

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

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 ?

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

Causal Criteria – Biological Plausibility

• Various mechanisms proposed – cadmium, male hormones, genetic mutations, immune dysfunction – but none clearly established

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 ??

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)

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