A systematic review and meta-analysis of tobacco use and prostate cancer mortality and incidence in prospective cohort studies

Abstract

Context: An association between tobacco smoking and prostate cancer (PCa) incidence and mortality was suggested in an earlier meta-analysis of 24 prospective studies in which dose-response associations and risks per unit of tobacco use were not examined.

Objective: We investigated the association between several measures of tobacco use and PCa mortality (primary outcome) and incidence (secondary outcome) including dose-response association.

Evidence acquisition: Relevant articles from prospective studies were identified by searching the PubMed and Web of Science databases (through January 21, 2014) and reference lists of relevant articles. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random effects methods. We also calculated population attributable risk (PAR) for smoking and PCa mortality.

Evidence synthesis: We included 51 articles in this meta-analysis (11823 PCa deaths, 50349 incident cases, and 4,082,606 cohort participants). Current cigarette smoking was associated with an increased risk of PCa death (RR: 1.24; 95% CI, 1.18-1.31), with little evidence for heterogeneity and publication bias. The number of cigarettes smoked per day had a dose-response association with PCa mortality (p=0.02; RR for 20 cigarettes per day: 1.20). The PAR for cigarette smoking and PCa deaths in the United States and Europe were 6.7% and 9.5%, respectively, corresponding to >10000 deaths/year in these two regions. Current cigarette smoking was inversely associated with incident PCa (RR: 0.90; 95% CI, 0.85-0.96), with high heterogeneity in the results. However, in studies completed in 1995 or earlier (considered as completed before the prostate-specific antigen screening era), ever smoking showed a positive association with incident PCa (RR: 1.06; 95% CI, 1.00-1.12) with little heterogeneity.

Conclusions: Combined evidence from observational studies shows a modest but statistically significant association between cigarette smoking and fatal PCa. Smoking appears to be a modifiable risk factor for PCa death.

Patient summary: Smoking increases the chance of prostate cancer death. Not smoking prevents this harm and many other tobacco-related diseases.

Keywords: Cigarettes; Meta-analysis; Prospective; Prostate cancer; Smoking.

Fig. 1

Flowchart of selection of studies. * When articles were indexed in both databases, only one was considered for further review. ** Two pooled studies because results from individual studies were included, three articles from studies on atomic bomb survivors (results might not generalize to the population), and four articles from two studies because there were few nonsmokers among study participants. *** Some results were provided, but the information was not sufficient to be included in the meta-analysis.

Fig. 2

The association between tobacco smoking at baseline and prostate cancer mortality in cohort studies. CI = confidence interval; NR = not reported; RR = relative risk. Huxley [12] and Rohrmann [72] had two subpopulations.

Fig. 3

The association between amount of cigarette smoking at baseline and prostate cancer mortality using the meta-regression method. The relative risk (RR) (95% confidence interval) calculated using this model for smoking one cigarette per day was 1.006 (1.001– 1.010) ( p = 0.02). The RR for other selected amount of cigarette smoking per day was as follows: 20 cigarettes, 1.20; 30 cigarettes, 1.25; and 40 cigarettes, 1.31 (RR = 0.0057994 × number of cigarettes smoked per day + 1.079222).