# Prostate cancer in firefighting and police work: a systematic review and meta-analysis of epidemiologic studies

Jeavana Sritharan, Manisha Pahwa, Paul Demers, Shelley Harris, Donald Cole, Marie-Élise Parent

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Jeavana Sritharan, Manisha Pahwa, Paul Demers, Shelley Harris, Donald Cole, et al., Prostate cancer in firefighting and police work: a systematic review and meta-analysis of epidemiologic studies. *Environmental Health, 2017, 16 (1), pp.124. 10.1186/s12940-017-0336-z*. pasteur-01854618

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# Prostate cancer in firefighting and police work: a systematic review and meta-analysis of epidemiologic studies

Jeavana Sritharan¹,²* ID, Manisha Pahwa¹, Paul A. Demers¹,²,³,⁴*, Shelley A. Harris¹,⁴,⁵, Donald C. Cole⁴ and Marie-Elise Parent⁶

**Abstract**

**Objectives:** We conducted a systematic review and meta-analysis to evaluate potential associations between firefighting and police occupations, and prostate cancer incidence and mortality.

**Methods:** Original epidemiological studies published from 1980 to 2017 were identified through PubMed and Web of Science. Studies were included if they contained specific job titles for ever/never firefighting and police work and associated prostate cancer risk estimates with 95% confidence intervals (CI). Study quality was assessed using a 20-point checklist. Prostate cancer meta-risk estimates (mRE) and corresponding 95% CIs were calculated for firefighting and police work separately and by various study characteristics using random effects models. Between-study heterogeneity was evaluated using the I² score. Publication bias was assessed using Begg's and Egger's tests.

**Results:** A total of 26 firefighter and 12 police studies were included in the meta-analysis, with quality assessment scores ranging from 7 to 19 points. For firefighter studies, the prostate cancer incidence mRE was 1.17 (95% CI = 1.08–1.28, I² = 72%) and the mortality mRE was 1.12 (95% CI = 0.92–1.36, I² = 50%). The mRE for police incidence studies was 1.14 (95% CI = 1.02–1.28; I² = 33%); for mortality studies, the mRE was 1.08 (95% CI = 0.80–1.45; I² = 0%). By study design, mREs for both firefighter and police studies were similar to estimates of incidence and mortality.

**Conclusion:** Small excess risks of prostate cancer were observed from firefighter studies with moderate to substantial heterogeneity and a relatively small number of police studies, respectively. There is a need for further studies to examine police occupations and to assess unique and shared exposures in firefighting and police work.

**Keywords:** Firefighters, Police, Occupation, Prostate cancer risk, Incidence, Mortality, Meta-analysis, Systematic review, Epidemiology

**Background**

Prostate cancer is one of the most commonly diagnosed cancers in men worldwide but its etiology remains poorly understood [1–5]. The only established risk factors for prostate cancer are older age, positive family history of prostate cancer, and African-American ethnicity [1, 2, 4, 5]. There is some evidence linking prostate cancer to differences in socioeconomic status, increased height, increased

obesity, reduced physical activity, and active smoking and alcohol use [3, 5–10]. There is growing evidence that occupation may be a risk factor, and previous studies have shown increased risks associated with employment in agriculture/farming, management and administration, rubber production, metal work, and transportation [11–13]. Some studies have also suggested associations between prostate cancer risk and employment in protective services occupations [11, 12, 15–17].

Protective services occupations include firefighting, police, military, and other groups (eg. security guards). Previous epidemiological studies have demonstrated consistent associations between firefighting and different

<footnote>* Correspondence: jeavana.sritharan@occupationalcancer.ca;
paul.demers@cancercare.on.ca
¹Occupational Cancer Research Centre, Cancer Care Ontario, 525 University Avenue, Toronto, ON M5G 2L3, Canada
Full list of author information is available at the end of the article</footnote>
types of cancer, with some evidence for prostate cancer [14]. In 2007, the International Agency for Research on Cancer (IARC) classified firefighting as “possibly” carcinogenic to humans (IARC Group 2B) [16]. IARC’s evaluation was based on evidence from 42 epidemiological studies, including two previous meta-analyses on firefighting and cancer [14, 18]. Based on studies published at the time, IARC evaluated multiple cancer sites and identified statistically significant increased risks of prostate cancer, testicular cancer, and non-Hodgkin lymphoma [16]. Since the IARC evaluation, 11 new studies have been published that included assessments of prostate cancer risk in firefighters. Relatively less is known about prostate cancer risk in police occupations, as this group is often understudied and findings have been inconsistent [11, 12, 15, 19, 20].

Only one meta-analysis, published over a decade ago, focused on firefighting and cancer risks that included prostate cancer [14]. This study found a significant association with prostate cancer incidence (summary risk estimate: 1.28, 95% CI: 1.15–1.43) based on evidence from 6 cohort studies [14]. Recently, a narrative review examined cancer risk in police work. Eight studies reported on prostate cancer risk in police work, with mixed findings [15]. The objective of the present systematic review and meta-analysis was to evaluate the quality of the epidemiological evidence on firefighting and police employment in association with prostate cancer incidence and mortality, and to conduct a quantitative synthesis. Based on the availability of epidemiologic literature, this meta-analysis focused on firefighting and police work, and not protective services as a whole.

# Material and methods

## Search strategy

A search was conducted on PubMed and Web of Science to identify epidemiological studies published between January 1980 and December 2017 in English or French about employment in firefighting and police occupations, and risk of prostate cancer. Various combinations of MeSH terms were used to search for studies that included firefighter and police occupations (firefighting OR firefighter OR fire fighter OR fire OR police OR police officer OR policeman OR policemen) and that reported on associations with prostate cancer risk (prostate OR prostate neoplasm OR neoplasm OR cancer). Cited references in individual papers and review papers that resulted from the search were used to identify any additional studies.

## Inclusion criteria

To be included in the meta-analysis, articles must have reported results for original case–control or cohort studies that contained specific job titles related to ever/never

firefighting and police work and that examined associated prostate cancer incidence and/or mortality using any type of relative risk estimator (hazard ratio (HR), odds ratio (OR), relative risk (RR), standardized mortality ratio (SMR), or standardized incidence ratio (SIR)) with corresponding 95% confidence intervals. Reviews, meta-analyses, editorials, and experimental studies were excluded. For any articles with overlapping study populations, only the most recently published study with prostate cancer incidence and/or mortality results was included. Furthermore, studies were excluded if reported risk estimates were only based on internal comparisons between different occupational groups rather than based on comparisons to the general population. Titles and abstracts were initially screened for eligibility, and for those eligible, full-text articles were reviewed.

## Data extraction

Information on author(s), date of publication, title, country of study, study design, number of cases/deaths and controls/non-cases, data collection method, effect sizes and 95% CIs for prostate cancer, and covariates was extracted from and tabulated for each study included in the meta-analysis. Effect sizes and 95% CIs recorded from included studies were for ever vs. never firefighter or police employment in models that were adjusted for the maximum number of potentially confounding variables.

## Quality assessment

The quality of each study included in the meta-analysis was independently assessed by two authors (JS and MP) using a modified quality assessment checklist by Downs and Black [21]. Checklist items that were irrelevant to observational studies were omitted, resulting in a maximum of 20 achievable points for reporting (9 points), external validity (2 points), internal validity (bias and confounding) (8 points), and power (1 point) [21]. Any disagreement of ratings was discussed and a consensus was arrived at mutually or by consulting a third author, if earlier consensus could not be reached.

## Statistical analysis

Reported ORs, HRs, RR, SIRs, and SMRs were considered as RR in meta-analyses and used in forest plots. A random effects model was used to calculate meta-risk estimates (mREs) in all meta-analyses due to potential variance in effect sizes between the included studies. mREs were calculated separately for firefighting and police occupations and prostate cancer risk. mREs were calculated for subgroups based on the following characteristics: incidence versus mortality, study design (i.e. cohort versus case–control, and administrative linkage-based studies,
defined as large studies that used multiple linked adminis-
trative databases, e.g. census data and tumour registries.

For each mRE, heterogeneity was evaluated using the
I² statistic. The I² statistic is a percentage that describes
the variation between studies that is not due to chance
[22]. Two-sided *p*-values for the I2 statistic were re-
ported. Ninety-five percent confidence intervals for the
I2 statistic were calculated to address small numbers of
included studies (N < 5) in some subgroup meta-
analyses. In addition, the Galbraith plot was used to
visualize if individual studies fell within or outside of the
95% confidence region. Studies outside of the 95% confi-
dence region can contribute to high heterogeneity.
These studies were removed in sensitivity analyses to
evaluate the impact of decreased heterogeneity on
mREs [23].

Begg's test and Egger's test were used to assess publi-
cation bias. Begg's test uses the correlation between
ranks of effect sizes and variances, whereas Egger's test
uses a funnel plot to plot the effect estimates against
sample size [24, 25]. All statistical analyses were
performed using STATA version 14.2 (StataCorp LLC,
College Station, USA).

Results

The literature search resulted in 366 unique studies pub-
blished in English or French. Based on the screening of
titles and abstracts, 318 (87%) were excluded due to non-
observational/non-human studies, missing job titles, miss-
ing effect estimates for prostate cancer, duplicate studies,
or irrelevancy to the objective of this meta-analysis. Of the
remaining 48 studies that were obtained in full text, 17
were excluded because they did not include reports of rela-
tive risks for prostate cancer with 95% CIs, had overlapping
study populations, or were studies of military workers. As
a result, 31 unique studies were included (Fig. 1).

Of these, 24 were cohort and seven were case–control
studies. Nineteen studies only included investigations of
firefighters (Table 1) and five focused on police workers
(Table 2); seven contained investigations of both fire-
fighters and police workers (Table 3). In all studies that
included firefighters (N = 26), there were 5712 incident
cases of prostate cancer and 428 deaths from prostate
cancer. In all studies that included police workers
(N = 12), there were 1510 incident cases and 49 deaths.
The characteristics of each included study are summa-
rized in Tables 1 (firefighters), 2 (police workers), and 3
(both). Covariates included in the risk estimates selected
from each of the seven case–control studies are shown
in Additional file 1: Table S1.

Of all the firefighter studies, 2 pairs of studies (Ma et al.,
2005 & Ma et al., 2006; Demers et al., 1992 & Demers et
al., 1994) [26–29] examined the same respective popula-
tions but reported on different prostate cancer outcomes
(incidence and mortality). In the meta-analyses of prostate
cancer incidence and mortality in firefighters, respective
results from both pairs of studies were retained and used.
Two studies [30, 31] published results for both prostate
cancer incidence and mortality, and each estimate was
used [31, 32]. For the police studies, [28, 29] reported on
the same populations with different outcomes of incidence
and mortality, and each estimate was used. Each incidence
and mortality outcome was used only in their respective
categories and not included together for any meta-risk
estimates.

Quality assessment

The overall quality assessment of all 31 included studies ranged from 5 to 19 points (Table 4). Scores were similar for firefighter, police, and firefighter and police studies across the different quality assessment categories. The mean score for reporting was 6 out of 9, based on clear

<figure><img src="image_3.png" /><figcaption>Fig. 1 Descriptive flow chart of study selection in this meta-analysis</figcaption></figure>
<table><caption>**Table 1** Characteristics of included studies on firefighting and prostate cancer risk (N = 19)</caption><thead><tr><th>Author/ Year</th><th>Location of Study</th><th>Study Design</th><th>Incidence or Mortality</th><th>Follow-up period</th><th>Number of Cases/ Deaths</th><th>Cohort Size/Total Number of Cases<sup>a</sup></th><th>Prostate Cancer Risk Estimates for Ever versus Never Employment<sup>b</sup></th></tr></thead><tbody><tr><td>Glass et al. 2016 [63]</td><td>Australia</td><td>Cohort</td><td>Incidence</td><td>1980–2011</td><td>478</td><td>30, 057</td><td>SIR 1.31, 95% CI 1.19–1.43</td></tr><tr><td>Brice et al. 2015 [64]</td><td>France</td><td>Cohort</td><td>Mortality</td><td>1979–2008</td><td>17</td><td>10, 829</td><td>SMR 0.54, 95% CI 0.31–0.86</td></tr><tr><td>Daniels et al. 2014 [32]</td><td>USA</td><td>Cohort</td><td>Incidence; Mortality</td><td>1950–2009</td><td>1261 cases 282 deaths</td><td>29, 993 29, 993</td><td>SIR 1.03, 95% CI 0.98–1.09; SMR 1.09, 95% CI 0.96–1.22</td></tr><tr><td>Pukkala et al. 2014 [17]</td><td>Denmark, Finland, Iceland, Norway and Sweden</td><td>Cohort (linkage)</td><td>Incidence</td><td>1961–2005</td><td>660</td><td>16, 422</td><td>SIR 1.13, 95% CI 1.03–1.22</td></tr><tr><td>Ahn et al. 2012 [65]</td><td>Korea</td><td>Cohort</td><td>Incidence</td><td>1996–2007</td><td>9</td><td>33, 416</td><td>SIR 1.32, 95% CI 0.60–2.51</td></tr><tr><td>Ma et al. 2006 [27]</td><td>USA</td><td>Cohort</td><td>Incidence</td><td>1981–1999</td><td>209</td><td>34, 796</td><td>SIR 1.10, 95% CI 0.95–1.42</td></tr><tr><td>Ma et al. 2005 [26]</td><td>USA</td><td>Cohort</td><td>Mortality</td><td>1972–1999</td><td>21</td><td>34, 796</td><td>SMR 1.08, 95% CI 0.67–1.65</td></tr><tr><td>Baris et al. 2001 [66]</td><td>USA, USA</td><td>Cohort</td><td>Mortality</td><td>1925–1986</td><td>31</td><td>7, 789</td><td>SMR 0.96, 95% CI 0.68–1.37</td></tr><tr><td>Bates et al. 2001 [67]</td><td>New Zealand</td><td>Cohort</td><td>Incidence</td><td>1977–1995</td><td>11</td><td>4, 221</td><td>SIR 1.08, 95% CI 0.50–1.90</td></tr><tr><td>Tornling et al. 1994 [31]</td><td>Sweden</td><td>Cohort</td><td>Incidence; Mortality</td><td>1951–1986</td><td>28 cases 14 deaths</td><td>1, 116 1, 091</td><td>SMR 114, 95% CI 76–165; SMR 121, 95% CI 66–202</td></tr><tr><td>Aronson et al. 1994 [68]</td><td>Canada</td><td>Cohort</td><td>Mortality</td><td>1950–1989</td><td>16</td><td>5, 373</td><td>SMR 132, 95% CI 76–215</td></tr><tr><td>Giles et al. 1993 [69]</td><td>Australia</td><td>Cohort</td><td>Incidence</td><td>1980–1989</td><td>5</td><td>2, 865</td><td>SIR 2.09, 95% CI 0.67–4.88</td></tr><tr><td>Guidotti 1993 [70]</td><td>Canada</td><td>Cohort</td><td>Mortality</td><td>1927–1987</td><td>8</td><td>3, 328</td><td>SMR 146.1, 95% CI 63.1–287.9</td></tr><tr><td>Beaumont et al. 1991 [33]</td><td>USA</td><td>Cohort</td><td>Incidence</td><td>1940–1982</td><td>8</td><td>3, 066</td><td>RR 0.38, 95% CI 0.16–0.75</td></tr><tr><td>Grimes et al. 1991 [71]</td><td>USA</td><td>Cohort</td><td>Mortality</td><td>1969–1988</td><td>4</td><td>205</td><td>PRR 2.6, 95% CI 1.4–5.0</td></tr><tr><td>Vena & Friedler 1987 [72]</td><td>USA</td><td>Cohort</td><td>Mortality</td><td>1950–1979</td><td>5</td><td>470</td><td>SMR 0.71, 95% CI 0.23–1.65</td></tr><tr><td>Tsai et al. 2015 [73]</td><td>USA</td><td>Case-control (linkage)</td><td>Incidence</td><td>1988–2007</td><td>1397</td><td>3, 996</td><td>OR 1.45, 95% CI 1.25–1.69</td></tr><tr><td>Kang et al., 2008 [74]</td><td>USA</td><td>Case-control (linkage)</td><td>Incidence</td><td>1986–2003</td><td>577</td><td>285, 964</td><td>SMR 1.05, 95% CI 0.88–1.24</td></tr><tr><td>Krstev et al. 1998 [75]</td><td>USA</td><td>Case-control</td><td>Incidence</td><td>1986–1989</td><td>12</td><td>981</td><td>OR 3.34, 95% CI 1.13–9.91</td></tr></tbody></table>

and detailed reporting of aims/hypotheses, outcomes measures, participant information, confounder information, and loss to follow-up. Studies were generally found to be externally valid, and there was minimal bias.

Studies of firefighters had higher scores for confounding factors than studies of police workers. Only one study reported a power calculation making it difficult to evaluate this category.

<footnote><sup>a</sup>cohort size represents the total sample size in only cohort studies, and the total number of cases is only applicable to case-control studies</footnote>

<footnote><sup>b</sup>HR – hazard ratio, SIR – standardized incidence ratio, SMR – standardized mortality/morbidity ratio, RR – relative risk, PRR – proportionate risk ratio, OR – odds ratio, NR – not reported</footnote>
<table><caption>**Table 2** Characteristics of included studies on police work and prostate cancer risk (N = 5)</caption><thead><tr><th>Author/Year</th><th>Location of Study</th><th>Study Design</th><th>Incidence or Mortality</th><th>Follow-up Period</th><th>Number of Cases/Deaths</th><th>Cohort Size/Total Number of Cases<sup>a</sup></th><th>Prostate Cancer Risk Estimates for Ever versus Never Employment<sup>b</sup></th></tr></thead><tbody><tr><td>Vena et al. 2014 [19]</td><td>USA</td><td>Cohort</td><td>Mortality</td><td>1980–2005</td><td>31</td><td>3, 424</td><td>SMR 1.18, 95% CI 0.80–1.67</td></tr><tr><td>Gu et al. 2011 [76]</td><td>USA</td><td>Cohort</td><td>Incidence</td><td>1976–2006</td><td>104</td><td>2, 234</td><td>SIR 0.88, 95% CI 0.72–1.07</td></tr><tr><td>Finkelstein 1998 [20]</td><td>Canada</td><td>Cohort</td><td>Incidence</td><td>1964–1995</td><td>85</td><td>22, 197</td><td>SIR 1.16, 95% CI 0.93–1.43</td></tr><tr><td>Forastiere et al. 1994 [77]</td><td>Italy</td><td>Cohort</td><td>Mortality</td><td>1973–1991</td><td>7</td><td>3, 868</td><td>SMR 0.77, 95% CI 0.31–1.50</td></tr><tr><td>Bouchardy et al. 2002 [78]</td><td>Switzerland</td><td>Case–control</td><td>Incidence</td><td>1980–1993</td><td>129</td><td>9, 126</td><td>OR 1.20, 95% CI 1.00–1.50</td></tr></tbody></table>

## Firefighter and prostate cancer meta-analyses

There were significantly elevated prostate cancer risks for firefighting occupations for incidence outcomes, cohort studies, and administrative linkage-based studies. For incidence studies, the mRE was 1.17 (95% CI: 1.08–1.28; $I^2$ = 72%, 95% CI: 55–82%, *p*-value <0.001; 19 studies) (Fig. 2); for mortality studies, it was 1.12 (95% CI: 0.92–1.36; $I^2$ = 50%, 95% CI: 0–76%, *p*-value = 0.04; 10 studies) (Fig. 3). In cohort studies, the prostate cancer mRE was 1.14 (95% CI: 1.03–1.26; $I^2$ = 67%, 95% CI: 46–80%, *p*-value <0.001; 18 studies) (Additional file 2: Figure S1). The meta-analysis of case-control studies resulted in an mRE of 1.27 (95% CI: 0.95–1.69; $I^2$ = 78%, 95% CI: 53–90%, *p*-value <0.001; 6 studies) (Additional file 3: Figure S2). The mRE for census or administrative linkage-based studies was 1.19 (95% CI: 1.06–1.34; $I^2$ = 61%, 95% CI: 0–85%, *p*-value = 0.04; 5 studies) (Additional file 4: Figure S3).

## Police work and prostate cancer meta-analyses

There were significantly elevated prostate cancer risks for police occupations by incidence outcomes and in case-control studies. The mRE for prostate cancer incidence studies was 1.14 (95% CI: 1.02–1.28; $I^2$ = 33%, 95% CI: 0–74%, *p*-value = 0.16; 9 studies) (Fig. 4) while the mRE for prostate cancer mortality studies was 1.08 (95% CI: 0.80–1.45; $I^2$ = 0%, 95% CI: 0–90%, *p*-value = 0.62; 3 studies) (Fig. 5). The mRE for case-control studies was higher compared to the mRE for cohort studies (case-control studies: mRE = 1.22, 95% CI: 1.03–1.44; $I^2$ = 0% (95% CI 0%–85%, *p*-value = 0.42; 4 studies) (Additional file 5: Figure S4) versus cohort studies: mRE = 1.10, 95% CI: 0.96–1.26; $I^2$ = 37%, 95% CI: 0–79%, *p*-value = 0.15; 7 studies) (Additional file 6: Figure S5). There were no administrative linkage-based studies of police workers and prostate cancer risk.

<table><caption>**Table 3** Characteristics of included studies on both firefighting and police work and prostate cancer risk (N = 7)</caption><thead><tr><th>Author/Year</th><th>Location of Study</th><th>Study Design</th><th>Incidence or Mortality</th><th>Follow-up Period</th><th>Number of Cases/Deaths</th><th>Cohort Size/Total Number of Cases<sup>a</sup></th><th>Prostate Cancer Risk Estimates for Ever versus Never Employment<sup>b</sup></th></tr></thead><tbody><tr><td>Sitharan et al, 2017b*</td><td>Canada</td><td>Cohort (linkage)</td><td>Incidence</td><td>1991–2011</td><td>165 firefighters; 325 police</td><td>1,100,000; 1,100,000</td><td>HR 1.17, 95% CI 1.01–1.36; HR 1.22, 95% CI 1.09–1.36</td></tr><tr><td>Zeegers et al. 2004 [11]</td><td>Netherlands</td><td>Cohort (linkage)</td><td>Incidence</td><td>1986–1993</td><td>709 firefighters; 693 police</td><td>58, 279; 58, 279</td><td>RR 0.59, 95% CI 0.05–6.33; RR 1.62, 95% CI 0.62–4.27</td></tr><tr><td>Demers et al. 1994 [28]</td><td>USA</td><td>Cohort</td><td>Incidence</td><td>1974–1989</td><td>66 firefighters; 28 police</td><td>2, 447; 1, 878</td><td>SIR 1.40, 95% CI 1.10–1.70; IDR 1.10, 95% CI 0.70–1.80</td></tr><tr><td>Demers et al. 1992 [29]</td><td>USA</td><td>Cohort</td><td>Mortality</td><td>1945–1989</td><td>30 firefighters; 11 police</td><td>4, 546; 3, 676</td><td>SMR 1.34, 95% CI 0.90–1.91; SMR 1.02, 95% CI 0.51–1.82</td></tr><tr><td>Sitharan et al. 2017a [79]</td><td>Canada</td><td>Case–control</td><td>Incidence</td><td>1995–1998</td><td>38 firefighters; 35 police</td><td>1, 737; 1, 737</td><td>OR 1.67, 95% CI 0.94–2.95; OR 1.15, 95% CI 0.66–1.99</td></tr><tr><td>Sitharan et al. 2016 [80]</td><td>Canada</td><td>Case–control</td><td>Incidence</td><td>1994–1997</td><td>53 firefighters; 12 police</td><td>760; 760</td><td>OR 0.73, 95% CI 0.53–1.01; OR 0.82, 95% CI 0.41–1.63</td></tr><tr><td>Sauve et al. 2016 [12]</td><td>Canada</td><td>Case–control</td><td>Incidence</td><td>2005–2009</td><td>26 firefighters; 45 police</td><td>1, 937; 1, 937</td><td>OR 1.72, 95% CI 0.88–3.37; OR 1.60, 95% CI 1.00–2.40</td></tr></tbody></table>

<footnote><sup>a</sup>cohort size represents the total sample size in only cohort studies, and the total number of cases is only applicable to case-control studies</footnote>

<footnote><sup>b</sup>HR – hazard ratio, SIR – standardized incidence ratio, SMR – standardized mortality/morbidity ratio, RR – relative risk, OR – odds ratio</footnote>

<footnote><sup>a</sup>cohort size represents the total sample size in only cohort studies, and the total number of cases is only applicable to case-control studies</footnote>

<footnote><sup>b</sup>HR – hazard ratio, SIR – standardized incidence ratio, SMR – standardized mortality/morbidity ratio, RR – relative risk, IDR – incidence density ratio, OR – odds ratio</footnote>

<footnote>*manuscript submitted and currently being revised for publication</footnote>
<table><caption>**Table 4** Quality assessment of included firefighter and police studies</caption><thead><tr><th rowspan="2">Quality Assessment Category</th><th rowspan="2">Maximum Attainable Score</th><th colspan="2">Studies on firefighters (n = 19)</th><th colspan="2">Studies on police workers (n = 5)</th><th colspan="2">Studies on both firefighters and police workers (n = 7)</th><th rowspan="2">All studies (n = 31)</th></tr><tr><th>Range</th><th>Mean</th><th>Range</th><th>Mean</th><th>Range</th><th>Mean</th><th>Mean</th></tr></thead><tbody><tr><td>Reporting</td><td>9</td><td>4–9</td><td>6.0</td><td>1–8</td><td>5.4</td><td>4–8</td><td>6.1</td><td>5.9</td></tr><tr><td>External Validity</td><td>2</td><td>1–2</td><td>1.8</td><td>0–2</td><td>1.6</td><td>1–2</td><td>1.6</td><td>1.7</td></tr><tr><td>Internal Validity: Bias</td><td>4</td><td>3–4</td><td>3.8</td><td>3–4</td><td>3.8</td><td>4</td><td>4</td><td>3.8</td></tr><tr><td>Internal Validity: Confounding</td><td>4</td><td>2–4</td><td>3.2</td><td>1–4</td><td>2.8</td><td>3–4</td><td>3.6</td><td>3.2</td></tr><tr><td>Power</td><td>1</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0–1</td><td>0.1</td><td>0.0</td></tr><tr><td>Total</td><td>20</td><td>10–19</td><td>14.8</td><td>5–18</td><td>13.6</td><td>12–18</td><td>15.4</td><td>14.6</td></tr></tbody></table>

## Between-study heterogeneity

There was high heterogeneity (72%) for the meta-analysis of all 19 firefighter incidence studies. As a sensitivity analysis, the Galbraith plot was used and one study [33], appeared outside of the 95% confidence region. Removal of this study resulted in a minimal change in heterogeneity (72 versus 69%, respectively). For the meta-analysis of the 10 mortality studies, there was moderate heterogeneity (50%). High heterogeneity was observed for the six case-control studies (78%), 18 cohort studies (67%) and the five administrative linkage-based studies (61%). When plotting these subgroups using the Galbraith plot, no studies appeared outside of the 95% confidence region.

For police studies, heterogeneity ranged from none to moderate. Moderate heterogeneity was observed for the nine incidence studies (33%) and seven cohort studies

(37%), but no heterogeneity (0%, 95% CI: 0–90%) was observed for the mortality (three studies) and case-control (four studies) subgroups. I² values of 0% are biased and imprecise, likely because of the small number of studies in these subgroups (n < 5) [34]. Using the Galbraith plot, none of the police studies appeared outside of the 95% confidence region.

## Publication bias

There was no evidence of publication bias according to Begg's test (p = 0.86) and Egger's test (p = 0.11) for the meta-analysis of all 19 firefighter incidence studies. No publication bias was evident for the 9 police incidence studies (Begg's test: p = 0.60, Egger's test: p = 0.68). There were also no statistically significant findings for

<figure><img src="image_4.png" /><figcaption>**Fig. 2** Forest plot and MRE of all included prostate cancer incidence studies on firefighters</figcaption></figure>
<figure><img src="image_5.png" /><figcaption>**Fig. 3** Forest plot and mRE of all included prostate cancer mortality studies on firefighters</figcaption></figure>

publication bias for mortality studies, case-control, cohort, and administrative linkage-based studies.

Discussion

In this meta-analysis of 31 epidemiological studies of protective services workers, nearly identical and small statistically significant excess risks of prostate cancer were found for ever working in firefighting and police work. Statistically significant and borderline prostate cancer mREs were found for firefighters in separate evaluations of incidence

studies, cohort studies, and administrative linkage studies, as well as in each meta-analysis of police worker incidence studies and case-control studies. Most studies were of average quality, with opportunities for improvement in reporting and study power assessment. As expected, case-control studies compared to cohort studies generally had more information on variables that can act as potential confounders of the firefighter/police work and prostate cancer associations. All case-control studies reported prostate cancer risk estimates that were adjusted for age;

<figure><img src="image_6.png" /><figcaption>**Fig. 4** Forest plot and mRE of all included prostate cancer incidence studies on police workers</figcaption></figure>
<figure><img src="image_7.png" /><figcaption>**Fig. 5** Forest plot and mRE of all included prostate cancer mortality studies on police workers</figcaption></figure>

most were also adjusted for ethnicity. Fewer case-control studies adjusted risk estimates for family history of prostate cancer and potentially confounding variables such as socioeconomic status, physical activity, height, obesity, active smoking, and alcohol consumption. Overall, findings from this meta-analysis support positive associations found between prostate cancer risk and firefighting in the epidemiological literature, and indicate a potential relationship with police work as well.

There are a few hypotheses that may explain why employment in protective services occupations could be associated with increased prostate cancer risk. Firefighting and police jobs are inherently dangerous occupations that involve stressful, and, at times, life-threatening, situations with exposure to multiple hazards [14–16]. Psychological stressors can influence biological processes and lead to decreased immune function, increased pro-inflammatory cytokine secretion, and cancer progression [15]. Shift work, which is common in protective services work, was significantly associated with increased prostate cancer risk in a recent meta-analysis of eight case-control and cohort studies [35]. Firefighters are also exposed to toxins released by fire and smoke including benzene, 1,3-butadiene, formaldehyde and at times can be exposed to other compounds such as radiation, diesel exhaust, asbestos, metals (arsenic and cadmium), and PAHs [14, 16, 27]. The chemical reactions during combustion and the age and type of building or material on fire can contribute to exposure to these compounds [16]. Police work involves fewer chemical exposures compared to firefighting, although exposure to ionizing radiation from radar devices is a concern for overall cancer risk [11, 12]. Firefighters and police workers may also be exposed to air pollution on the job, as ambient concentrations of ultrafine particles and NO₂ have been

previously linked to prostate cancer risk [36, 37]. Of the described chemical exposures, only x and gamma radiation, arsenic compounds, and cadmium compounds have been linked to prostate cancer by IARC based on limited evidence in non-occupational settings. However, IARC has classified benzene, ionizing radiation, diesel exhaust, asbestos, arsenic compounds, cadmium compounds, and air pollution as all Group 1 carcinogens, based on evidence for other cancer sites [38]. There is a need to further examine these chemical exposures in both firefighting and police work to understand if these exposures are involved in prostate cancer risk.

Evaluating potential associations between shift work and prostate cancer is an active area of ongoing research [39–41]. Shift work can disrupt the body's endogenous circadian rhythm (sleep-wake cycle) and contribute to increased susceptibility to acute and chronic diseases. However, the biological mechanisms that may be involved in prostate and other cancers have not been established [18, 42]. One hypothesis is that night shift work can lead to decreased melatonin, which can then lead to continuous testosterone production, influencing the growth and differentiation of prostate cancer cells [16]. In addition, decreased sunlight exposure in night shift workers reduces the production of vitamin D, thereby compromising the effects of vitamin D on suppressing the production of prostate cancer cells [16].

Psychological stress also has been linked to cancer progression, but there is limited evidence for how this impacts cancer promotion [43]. Firefighting and police work involve constant stressors that can potentially affect cancer progression, particularly prolonged stress over years of employment in these jobs [44]. A recent study on stress at work and cancer outcomes found that
the highest prevalence of stress at work was reported
among firemen when compared to other types of occu-
pations [45].

Another factor that may influence our meta-analysis
results is prostate cancer screening. Although prostate
specific antigen (PSA) testing varies across different
countries and within countries, it is believed that pro-
tective services workers have frequent and better access
to health resources compared to other workers, includ-
ing access to cancer screening [32]. In North America,
for example, firefighters are provided with health infor-
mation and recommendations on what to consider when
completing a health examination with their primary
physician, including recommendations for prostate can-
cer screening [46]. However, it is up to each fire depart-
ment to disseminate this information and ultimately up
to each firefighter to request screening from their pri-
mary physician. In this meta-analysis we found slightly
lower mortality mREs compared to incidence mREs for
firefighters and police officers. As increased screening of
prostate cancer leads to the identification of more early
stage cases (increased incidence), this may be indicative
of a screening effect. However, the mREs for both inci-
dence and mortality were so similar that it was difficult
to attribute these differences to screening. Also, prostate
cancer screening may not be of high importance in fire-
fighting compared to other cancers (ex. brain, bladder,
and colon) and health conditions that have been consist-
ently associated with firefighting. We evaluated study
estimates based on different follow-up periods defined
as pre-PSA period (prior to 1990 before the PSA test
was introduced), during the introduction of PSA testing
(early 1990s), and after the introduction of PSA testing
(late 1990s and onwards). Although we included studies
from different nations, most of the studies were North
American so we loosely defined the time periods based
on North America. We identified a number of pre-PSA
period firefighter studies and observed a meta-risk esti-
mate of 1.26 (95% CI 0.96–1.67) for these studies. For
firefighter studies that had follow-up periods during and
after the introduction of PSA testing, we observed a
meta-risk estimate of 1.13 (95% CI 1.02–1.25). It was
challenging to define firefighter study follow-up periods
as post PSA testing (late 1990s onwards) since most of
these studies had follow-up periods that overlapped the
early 1990s when PSA testing began. We identified only
a few firefighter studies that had later follow-up periods
(late 1990s and early 2000s) and observed a meta-risk
estimate of 1.58 (95% CI 1.09–2.29) for these studies.
Overall, we observed an elevated risk for firefighter stud-
ies that were conducted before the introduction of PSA
testing, and a statistically significant elevated risk for
firefighter studies that took place during and after the
introduction of PSA testing. These findings may be

representative of the increased screening that took place
over this time period. We attempted to evaluate police
studies as well but were limited as almost all included
police studies had follow-up periods overlapping periods
with and without PSA testing.

Our findings of a slight excess risk of prostate cancer
in firefighting and police services should be cautiously
interpreted. As expected, there was considerable hetero-
geneity between studies, particularly in subgroup meta-
analyses of police workers and prostate cancer risk
that involved small numbers of studies. This makes it
challenging to interpret mRE values with precision
[34]. Heterogeneity was likely due to differences in
study design and populations studied, follow-up years,
occupational exposure assessment and job coding,
and adjustment of relative risk values for known or
potential covariates. Specifically, there were differ-
ences in how the study populations were defined, in
terms of paid or unpaid work, full time vs. part time,
and eligible employment duration. Some heterogeneity
may also be attributed to different follow-up periods
in each study, especially those overlapping the pre
and post PSA era. The variation in age distribution
across included studies could also contribute to het-
erogeneity based on differences in how studies strati-
fied by age. Some studies had relatively younger
populations than other studies and we observed a
similar elevated meta-risk estimate for these younger
population studies as we did for the overall estimates
Publication bias was also considered, but was not rec-
ognized as a significant factor as a majority of the
included studies were cohort designs. The cohort
studies generally looked at multiple cancer sites as
outcomes, so it is unlikely that publication bias would
have been of concern based on solely prostate cancer
results.

A major strength of this meta-analysis is that it was
the first to assess prostate cancer risk in both firefighting
and police work, replete with subgroup analyses and as-
sessments of study quality, heterogeneity, and publica-
tion bias. This meta-analysis captured all previously and
newly published studies since the IARC evaluation of
firefighting in 2007, and also quantitatively evaluated
prostate cancer risk in police studies which had not been
done before. Firefighting and police work should be pri-
ority areas for investigation because these occupations
frequently involve exposure to multiple chemical, bio-
logical, physical, and psycho-social hazards. Exposure to
some hazards may be associated with increased risk of
prostate cancer, although the strength and consistency
of associations varies across studies and there are sub-
stantial research gaps. Altogether, this research can be
used to help identify opportunities for further research
on occupation and prostate cancer risk.
Other occupations of interest with respect to prostate cancer risk are military workers. While we initially sought to include military studies in this meta-analysis, they were ultimately not included because these studies were primarily based on specific historical events (ex. Gulf war) or internal comparisons between military groups [47–62]. This made it difficult to compare findings to other studies that did not focus on single events or that compared workers to the general population. Future assessments can separately consider military studies.

## Conclusions

Overall, the slight excess risks of prostate cancer in firefighting and police services found in this meta-analysis of 31 studies were generally robust to subgroup analyses by outcome (incidence and mortality) and study design. Our findings are important as they show the importance of prostate cancer incidence and mortality among protective services workers, and as this is the first meta-analysis to include both firefighting and police work and prostate cancer risk. The observed findings suggest that screening may not entirely explain our findings, but further investigation into actual screening rates and screening behaviours in firefighting and police work is warranted. Also, further investigations should be designed to assess specific exposures such as benzene, radiation, diesel exhaust, arsenic and cadmium compounds, PAHs, asbestos, and air pollution which are involved in firefighting. Little evidence on how they may relate to prostate cancer risk has been accrued. There is also a need for future studies to examine prostate cancer risk in police work given the small number of police workers published to date. By addressing these important issues in future studies, there will be better understanding on prostate cancer risk in firefighting and police work.

## Additional files

**Additional file 1: Table S1.** Covariates adjusted for in firefighter and police case-control studies (DOCX 12 kb)

**Additional file 2: Figure S1.** Forest plot and mRE of all included cohort studies on firefighters. (DOCX 285 kb)

**Additional file 3: Figure S2.** Forest plot and mRE of all included case-control studies on firefighters. (DOCX 137 kb)

**Additional file 4: Figure S3.** Forest plot and mRE of all included administrative linkage-based studies on firefighters. (DOCX 153 kb)

**Additional file 5: Figure S4.** Forest plot and mRE of all included cohort studies on police workers. (DOCX 175 kb)

**Additional file 6: Figure S5.** Forest plot and mRE of all included case-control studies on police workers. (DOCX 117 kb)

### Abbreviations

CI: Confidence Interval; HR: Hazard Ratio; IARC: International Agency for Research on Cancer; mRE: Meta-risk Estimate; OR: Odds Ratio; PSA: Prostate Specific Antigen; RR: Relative Risk; SIR: Standardized Incidence Ratio; SMR: Standardized Mortality Ratio

### Acknowledgements

We would like to acknowledge Sheila Kalenge's contribution to prostate cancer screening behaviours in firefighters.

### Data availability statements

All data generated or analyzed during this study are included in this published article.

### Funding

The corresponding author is supported by the Occupational Cancer Research Centre which is funded by the Canadian Cancer Society, Cancer Care Ontario and the Ontario Ministry of Health and Long-Term Care. Grant number 2014-703257.

### Authors' contributions

The corresponding author, JS, is the main contributor in the design and conceptualization of the study, analysis and interpretation of the data, drafting the work and revising content critically, final approval of the work to be published. MP contributed to the design and conceptualization of the study, analysis and interpretation of the data, drafting and revising the work critically, and final approval of the version to be published. PD contributed to the conceptualizing and design of the study, acquisition and interpretation of the data, drafting the work and revising content critically, and final approval of the work to be published. SH and DC contributed to the design and interpretation of the work, drafting and revising content critically, and final approval of the version to be published. MEP contributed to the design and conceptualization of the study, interpretation of the data, drafting and revising the work critically, and final approval of the version to be published.

### Ethics approval and consent to participate

Not Applicable.

### Consent for publication

Not Applicable.

### Competing interests

The authors declare that they have no competing interests.

## Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

### Author details

¹Occupational Cancer Research Centre, Cancer Care Ontario, 525 University Avenue, Toronto, ON M5G 2L3, Canada. ²Institute of Medical Science, University of Toronto, 525 University Avenue, Toronto, ON M5G 2L3, Canada.

³CAREX Canada, Simon Fraser University, Burnaby, Canada. ⁴Dalla Lana School of Public Health, University of Toronto, 525 University Avenue, Toronto, ON M5G 2L3, Canada. ⁵Population Health and Prevention, Cancer Care Ontario, 525 University Avenue, Toronto, ON M5G 2L3, Canada.

⁶INRS-Institut Armand-Frappier, University of Quebec, 531 Boulevard des Prairies, Laval, Quebec H7V 1B7, Canada.

Received: 20 September 2017 Accepted: 27 October 2017

Published online: 17 November 2017

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