Occupation and prostate Cancer risk: results from the epidemiological study of prostate cancer (EPICAP)

Our results are based on a large population-based case-control study, carefully and specifically designed to address occupational factors and PCa risk, with a particular interest for aggressive PCa.

Our results showed an increased risk of PCa mainly among specific Professional, technical and related Workers and among Administrative and Managerial Workers, while we observed a decreased risk among Service workers and among Production and Related Workers, Transport Equipment Operators and Labourers.

Among the existing literature that has investigated occupational factors and PCa risk, very few studies assessed the entire occupational history, provided information on duration of employment in each occupation [14,15,16, 18]. Most of them studied PCa risk based on longest or last occupation held while only two studies took into account the aggressiveness of PCa [11, 15].

We observed positive associations with overall and aggressive PCa for men who ever worked as Surveyors, draughtsmen and related technicians, particularly if they worked 10 years or more. Similar results were also found in a North American study based on death certificates of men from 24 US states (OR = 2.10 [1.30; 3.50]), even though duration was not assessed [17].

We also found positive associations for Medical, dental and veterinary workers with the highest risk observed for Medical doctors. Our findings are consistent with previous cohort studies from Canada [5] and Nordic countries [7, 8] that showed a moderated increased risk for Medical doctors. However, they were not able to assess duration and prostate cancer aggressiveness. This “Medical, dental and veterinary workers” group is made up of men of a higher SES which may explain the observed positive associations based on a higher screening behaviour. In fact, the prevalence of screening in the last 2 years before interview among the Medical, Dental and veterinary workers group was 100%. However, our results were more specifically observed for aggressive PCa, thus minimizing a potential detection bias.

Working in Administrative and Managerial occupations for 10 years or more has been associated with an increased risk of PCa in our study, particularly for Legislative officials and Government administrators and Managers. These occupational categories are consistently observed to be associated with prostate cancer in the literature [5, 7, 8, 11, 14,15,16, 20].

While several studies found an increased risk of PCa with Protective service workers category [7, 8, 16, 32] and for Firefighters [6, 14, 16], Police officers [6, 9, 15] and Members of the armed forces [6,7,8, 11, 14], we did not observe any association with the Protective service workers category. However, we observed an increased risk of aggressive PCa in Members of the armed forces for men who worked 10 years or more even though based on small numbers.

When considering working in the Fishermen, Hunters and Related Workers group for 10 years or more, we observed an increased risk for aggressive PCa, particularly for Fishermen, while a decreased risk of either an early or a late-onset of PCa (whether diagnosed before or after 50 years old) for these workers was reported in the Nordic Occupational Cancer (NOCCA) studies [7, 8].

We found a positive association with PCa risk for Production Supervisors and General Foremen as observed in two North American case-control studies [16, 17].

Some negative associations have also been observed in our study with Service Workers with conflicting results in the literature [5, 13, 16] and with Food and Beverage Processers, Blacksmiths, Toolmakers and Machine-Tool Operators, Material-Handling and Related Equipment Operators, Dockers and Freight Handlers as observed in other original studies [5,6,7,8, 12].

Unlike some previous studies and reviews, we did not find any association in our study with Farmers and Agricultural industry [5, 6, 15, 16, 19, 21, 22, 24], Heavy and toxic metal workers or Chemical workers, Metalwork and Chemical industry [5, 7, 14, 18, 21, 22, 24].

Although we were able to study PCa risk in a wide range of occupations ever occupied and by duration of employment in each job, we could not clearly identify specific occupational exposures related to each job held, which may entail exposure to several different factors such as chemical, physical or psychosocial factors. We could not either rule out that certain of our results are chance findings due to multiple testing. However, we chose not to use any methods of correction for multiple testing. Indeed, we adopted an exploratory research with a hypothesis-generating purpose and we wanted to avoid reducing the power too drastically due to low already prevalence of certain occupations [33, 34]. We believed that our results could be used as leads for future research related to specific occupational exposures. Still and all, several factors in the work environment may explain the associations between specific occupations and PCa observed in our study.

Several studies on night-shift work and prostate cancer suggest that night and rotating shift work may be associated with prostate cancer risk [25, 26, 35], particularly for long duration and aggressive prostate cancer, including the EPICAP study [36, 37]. This may be relevant across some occupations identified in our study that are concerned by night-shift work, such as Medical, dental and veterinary workers, Members of the armed forces or Fishermen. Indeed, prevalence of night shift work in those occupations was 33.4% in Medical, dental and veterinary workers, 44.4% in Members of the armed forces, and 62.5% in Fishermen, Hunters and Related Workers. In addition, the three occupational groups mentioned before are also subject to a consistent chronic stress that may impact cancer development, as observed in a recent study that found a link between workplace stress and PCa risk [38]. According to the authors, chronic stress may influence cancer development by activating the sympathetic nervous system leading to downregulation of cellular immune response, genomic instability and changing in testosterone levels.

Furthermore, sedentary behaviour and low physical activity in the workplace may have a negative impact on PCa risk through changes in testosterone levels, insulin-like growth factor and immune function [39]. Occupations related to that in our study are Administrative and managerial occupations. Also, these workers usually have a higher SES than blue collar workers, which leads to better access to health services and an increase PSA screening behaviour [40, 41], which may explain part of our results, specifically observed for non-aggressive prostate cancer. In fact, the prevalence of screening in the last 2 years before interview was 93.4% among Managers and 90% among Legislative Officials and Government Administrators.

There is growing evidence that PCa development may be due to specific chemical exposures in some occupations. Based on the results of our study, we can mention at least two occupations that could be concerned: Members of the armed forces who are usually exposed to pesticides, solvents, fuels (diesel exhaust), chemical/warfare agents, particulate matter, polychlorinated biphenyls, polycyclic aromatic hydrocarbons (PAHs) and Woodworkers mainly exposed to wood dust, PAHs and pesticides [10, 42, 43]. However, several other occupations that may be associated with chemical exposures could also be related to PCa. Assessing chemical exposures using job exposure matrix will help to go further for studying occupational exposures in PCa.

Our findings are based on data from the EPICAP study which presents several strengths either in the selection of the population or in the data collection.

Cases were identified in all cancer hospitals, either public or private, that recruited prostate cancer patients in the department of Hérault. In 2011, 770 new cases of prostate cancer, of which 75% aged less than 75 years old, were reported by the Hérault Cancer Registry. Considering that the number of cases observed in 2012–2013 will be similar, approximately 1150 new cases were expected during the study period (2012–2013). In fact, the recruitment of cases was exhaustive since the number of eligible cases identified over the study period in the EPICAP study was 1098, thus limiting a potential selection bias. Moreover, even though participation rate in cases was 75%, the age distribution and the Gleason score of the non-respondent cases were comparable to those of the respondent cases, thus limiting a potential survival bias (private communication from the Hérault Cancer Registry). We were able to evaluate PCa risk taking into account aggressiveness, using the Gleason score, which has rarely been considered in previous occupational studies. Controls were randomly selected from the general population of the department of Hérault using quotas on age (5 years) to reflect the age distribution of the cases. Moreover, quotas by SES have been established in order for our control group to reflect to the general population of the department of Hérault of the same age. After the selection process, the distribution by SES between the control group and the male general population of the department of Hérault was compared and no significant difference was found, indicating that no major selection bias by SES had occurred in the control population.

Moreover, EPICAP is a population-based case-control study that has been specifically designed to study the role of environmental and occupational factors in PCa risk. We performed a standard lifetime work history that gathered information covering all jobs held more than 6 months throughout life. The job titles were derived from detailed information, such as starting and ending dates of each job held and specific tasks, provided by men about their entire employment history, this might have entailed errors. However, comparison between historical employment records and self-reported occupational questionnaires have generally shown a high concordance [44]. The coding of occupations have been performed by an industrial hygienist, blinded to the subject’s case/control status, thus reducing differential bias. Finally, we were able to consider the influence of duration of employment in each occupation on our results, by interval of 10 years because PCa latency can be very long, since lifetime occupational history was available for all subjects.

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