In the early 1980s we conducted a population-based case–controlstudyinMontreal, Canada, to explore pos- sible associations between hundreds of occupational sub- stances and multiple cancer sites, including lung cancer (Study I). In the late 1990s, we carried out a similar studyin the same area, this time focusing on lung cancer (Study II). The present set of analyses, conducted in both studies, examines the risk of lung cancer associated with occupa- tional exposure to wood dust, while controlling for major confounders, including smoking and other occupational exposures. An initial analysis of Study I concerning the as- sociation between wood dust and several sites of cancer, including lung, was previously published . It is ana- lyzed here in more detail, as is the data from Study II, to be able to contrast results from the two studies, and more importantly to provide more valid and comprehensive re- sults than those previously published. Namely, the present analysis of Study I improves on the previous analysis in several regards. First, there have been re-evaluations of exposure assessments to some subject files. Second, the previous publication only reported results using cancer controls; this one reports results using both the cancerand population controls. Third we have improved the stat- istical modeling of confounders, most notably smoking history.
The study on which this analysis was based was de- signed primarily to examine the risk of lung cancer re- lated to occupational exposures. As in any case–controlstudy of lung cancer, the proportion of cases who were lifelong nonsmokers was very low, and even though the total number of cases in our study was over 1200, the number of never smoking cases was only 44. This is the main limitation of this study, although this is somewhat palliated by the fact that exposure to ETS is quite preva- lent. As a result of the low numbers, the estimates of OR from our analysis alone are quite imprecise. But this is typical of most studies of ETS andcancer. We believe that our results are useful, not only because they stand by themselves, but because they may be included in fu- ture meta-analyses or pooled analyses, which may accu- mulate sufficient numbers of subjects to achieve more precise results. In addition, to our knowledge, there is
Both positive and negative associations between physical activity and PCa risk have been previously reported in observational epidemio- logical studies ( WCRF and AICR, 2014; Wekesa et al., 2015 ). Higher physical activity levels among individuals with access to natural out- door environments have been observed repeatedly ( Chaix et al., 2014; Gong et al., 2014; Li et al., 2008; Richardson et al., 2013 ). Ina Canadian survey, positive associations were observed between greenness and physical activity independent of income level ( McMorris et al., 2015 ). While there is some evidence and expert consensus to suggest that liv- ing in greener areas can facilitate physical activity ( Lee and Maheswaran, 2011 ), the evidence of a direct effect remains weak ( Maas et al., 2008 ). However, the type of greenness is an important fac- tor in determining whether and how it may in ﬂuence health ( Bixby et al., 2015 ). This could explain why some studies found that access to gen- eral greenness had no impact on individuals' levels of physical activity, whereas studies that restricted the measure of greenness to speci ﬁc types of environments - such as parks or sports grounds - reported im- proved physical activity behavior with increased accessibility ( Wendel- Vos et al., 2004 ). Adjusting for different types of self-reported physical activity levels, including recreational, had little in ﬂuence on our ﬁndings but the variables used were relatively crude.
be responsible for its effect. However, early evidence of elevated lung cancerrisk was also found in workers exposed to soluble nickel (59).
Recent epidemiology studies confirm the likelihood that more than one form of nickel increases lung cancerrisk, but evidence has increasingly been shifting away from insoluble nickel compounds in favour of soluble nickel. Most occupational cohorts with quantitative exposure estimates indicate that soluble nickel is the most important risk factor for lung cancer (10, 47, 49). Ina detailed quantitative re-assessment of exposure estimates, a highly consistent exposure- dependent risk was reported for exposure to soluble nickel species (23, 46), with significantly elevated risk estimates at higher doses (OR=3.8, 95%CI=1.6-9.0). After adjustment for soluble nickel exposureand smoking, the effects of insoluble (sulfidic and oxidic) forms of nickel were elevated (between 0.9 and 2.2, depending on exposure level) but always insignificant and without any dose-related trends. Similarly, exposure-dependent risk was found in Norwegian workers exposed to soluble nickel alone or in combination with other species (47). Strong evidence of the effects of soluble nickel species were also found in the Finnish cohort, where workers were exposed to either primarily soluble or insoluble nickel species. While both forms of nickel imposed a significantly increased risk after 20 years’ latency, soluble nickel was consistently associated with a higher incidence of lung cancer among exposed workers (49).
Our study presents several important strengths. This is the largest study to date to assess the association between sunlightexposure, using an assessment protocol that takes into account individual sunlight-related behavior, and PCa. Moreover, the exposure assessment covered the en- tire adulthood period, something rarely achieved in the past. Cases were histologically confirmed, and information was collected as part of face-to-face interviews. Participa- tion rates in the study were relatively good, compared to those often observed in similar studies. We were able to compare socio-demographic characteristics of eligible men who declined to participate in the study, to those of study subjects; only slight differences were observed, suggesting that strong selection bias was not at play. We collected information on a wide range of potential confounders and considered these in our analyses. This included the use of solar protection, which few studies have been able to take into account [18,20].
Methods: Cases were 1937 men with incident prostatecancer, aged ≤75 years, diagnosed across French hospitals in the Montreal area between 2005 and 2009. Concurrently, 1995 population controls from the same residential area and age distribution were randomly selected from electoral list of French-speaking men. Detailed lifestyle and medical histories, and anthropometric measures, were collected during in-person interviews. Prevalence of MetS components (type 2 diabetes, high blood pressure, dyslipidemia and abdominal obesity) was estimated at 2 years before diagnosis for cases/ interview for controls, and at ages 20, 40, 50 and 60. Logistic regression was used to estimate odds ratios (OR) and 95 % confidence intervals for the association between MetS andprostatecancerrisk. Results: A history of MetS ( ≥3 components vs <3) was associated with a reduced risk of prostatecancer (OR = 0.70 [0.60, 0.82]) after considering potential confounders. The negative association was particularly pronounced with a young age ( ≤40 years) at MetS onset (OR = 0.38 [0.16-0.89]), did not vary according to prostatecancer
We investigated whether exposure to DDE or PCB-153 was associated with PCa aggressiveness. Gleason score and clinical stage at diagnosis are powerful predictors of the aggressiveness of PCa. In particular, patients with high-grade Gleason scores have lower metastasis-free survival and higher PCa-specific mortality. PCB-153 exposure appeared to be negatively associated with low-grade Gleason score. Screening procedures may have intro- duced distortions in the associations observed between exposures of interest andcancer outcomes if fewer cases had been included in the absence of screening (Weiss 2003). In our study population, the prevalence of PSA screening among PCa cases with low-grade Gleason score was 76.7% but among PCa cases with a high-grade score, it was only 10%. Also, we found that additional adjust- ment for PSA screening did not change the risk estimates (data not shown). These various observations suggest that PCB-153 exposure may truly decrease the occurrence of low- grade PCa without changing the occurrence of high-grade forms. Koutros et al. (2013) have suggested that the different associations between chemical exposures (i.e., pesticides) and PCa aggressiveness may be consequences of different roles of such exposures in the prostatic carcinogenesis (for example, earlier initiation stage vs. prostatecancer progres- sion). However, it has not been established that nonaggressive and aggressive forms of PCa are etiologically and pathogenically similar.
Historically, the most common histological subtype of lung cancer was adenocarcinoma in women and squa- mous cell carcinoma in men. The predominance of adenocarcinoma in women was concomitant with lower tobacco consumption anda higher proportion of non- smokers than in men with lung cancer [ 5 – 11 ]. Since the early 1990s, the proportion of adenocarcinoma has in- creased in women andin men with lung cancerand it now exceeds all other histological subtypes in both sexes [ 12 ]. This increase in the proportion of adenocarcinomas among lung cancer patients has been considered a con- sequence of a decline in smoking, which was found to be consistently associated with a lower risk of lung adenocarcinoma than squamous cell or small cell car- cinoma [ 13 – 17 ]. It has also been suggested that the increasing proportion of adenocarcinoma among lung cancer patients might be due to changes in smoking behaviours and type of cigarette (i.e., lower tar and nicotine content of cigarettes, and increasing use of filter cigarettes) leading to deeper inhalation of to- bacco smoke and more extensive exposure of periph- eral lung tissue to small particles, prone to the development of adenocarcinomas [ 18 , 19 ]. However, the use of a filter cigarette, the inhalation pattern or the type of tobacco smoked were not found to differ by histological subtype ina previous study among French women [ 17 ]. Thus, the role of smoking pat- terns on risk by histological subtype of lung cancer among women requires clarification.
dairies through proteins on one hand and vitamin D on the other is most likely very limited.
On the other hand, the association between CD and sun exposure could also be causal, as suggested by several epidemiological and biological data. Firstly, there is a reproducible North-South gradient of CD incidence which has been found in the USA, Scotland and France 9, 14, 15 . Sun exposure might well explain the North-South gradient found in these countries. Secondly, the geographic distribution of multiple sclerosis (MS) appears to be similar to that of CD in France and several lines of evidence suggest that sun exposure protects from MS 16 . A strong inverse correlation between UV radiation and MS prevalence has been found ina geographical study performed in Australia 5 . Acase-controlstudy has shown that exposure to the sun in infancy may protect against multiple sclerosis 6 . It has also been shown that people with the highest blood levels of vitamin D had the lowest risks of MS 7 . Furthermore, results from a cohort study of 187,500 nurses showed that women who consumed at least the current daily recommended dose of vitamin D have a lower risk of developing MS 8 . Exposure to the sun may explain the French North-South gradient of MS and CD. Thirdly, there is a biological plausibility for our findings 17 . Sun and vitamin D have been found to act as immune regulators. UV radiation and vitamin D have been shown to induce regulatory T cell function 18 . UV radiation induces immune suppression via induction of IL-4 and IL-10 and suppression of IL-12 production 19 . 1,25-dihydroxyvitamin D inhibits dendritic cell differentiation and maturation, which induces a shift in T cell differentiation from Th1 and Th17 to a Th2 phenotype 20 . Recent studies have found that vitamin D is also a key regulatory factor of innate immunity. Vitamin D, produced in response to UV radiation, stimulates the production of
The members of the EPICAP study group are listed in the Acknowledgment section.
Chronic inflammation may play a role inprostatecancer carcinogenesis. In that context, our objective was to investigate the role of nonsteroidal anti- inflammatory drugs (NSAIDs) inprostatecancerrisk based on the EPICAP data. EPICAP is a population- based case–controlstudy carried out in 2012–2013 (département of Hérault, France) that enrolled 819 men aged less than 75 years old newly diagnosed for prostatecancerand 879 controls frequency matched to the cases on age. Face to face interviews gathered information on several potential risk factors including NSAIDs use. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using unconditional logistic regression models. All- NSAIDs use was inversely associated with prostatecancer: OR 0.77, 95% CI 0.61–0.98, especially in men using NSAIDs that preferentially inhibit COX- 2 activity (OR 0.48, 95% CI 0.28–0.79). Nonaspirin NSAIDs users had a decreased risk of prostatecancer (OR 0.72, 95% CI 0.53–0.99), particularly among men with an aggressive prostatecancer (OR 0.49, 95% CI 0.27–0.89) andin men with a personal history of prostatitis (OR 0.21, 95% CI 0.07–0.59). Our results are in favor of a decreased risk of prostatecancerin men using NSAIDs, par- ticularly for men using preferential anti- COX- 2 activity. The protective effect of NSAIDs seems to be more pronounced in aggressive prostatecancerandin men with a personal history of prostatitis, but this needs further investigations to be confirmed.
A major strength of our study is the large study popu- lation that included 2060 biopsy-confirmed lung cancer cases, thereby representing the largest case series pub- lished to date. Unlike most previous studies that were based on occupational cohorts (2, 6–10, 12 –19, 22, 23, 25, 26), our case–controlstudy was population-based and thus evaluated a wide range of levels of exposure to formaldehyde, as well as considered the entire occu- pational history. The lifetime prevalence of exposure to formaldehyde was high, 25.0% among all controls and 24.9% among all cases, leading to relatively large numbers of exposed subjects. Participation rates were relatively high in both studies I and II, thereby reducing the potential for selection bias (48). Furthermore, we presented results separately for women, stratified our analyses according to smoking levels, and estimated the associations according to histological subtypes, thus providing results for subgroups not often analyzed in previous studies. Finally, an important strength of our study is that it took into account many important potential confounders such as age, ethnocultural origin, income, education, and the main lung carcinogens, ie, smoking using the CSI and occupational lung carcino- gens (asbestos and silica).
To investigate the association between occupational exposure as a painter and lung cancerrisk, ORs and 95% CIs were computed using unconditional logistic regression models. Two exposure metrics were considered: ever vs never being employed as a painter, and the duration of employment as painters (years). Duration of employment was categorised into tertiles (1–5, 6–17, >17 years) based on the duration distribution among control subjects that had worked as painters. Subjects who were never employed as painters were considered as the reference category in analysis for both expo- sure metrics. Models were adjusted for study (individual centres of the IARC studyin Central and Eastern Europe and the UK (INCO) were treated as separate studies), age, cigarette pack- years (cPY), time- since- quitting smoking cigarettes (categorised as current smokers; quitting 2–7, 8–15, 16–25, 26–35, 36+ years before diag- nosis/interview and never- smokers), ever- employment (yes/no) in an industry or occupation with known (list A) or suspected (list B) association with the risk of lung cancer. 17 18 Painters were excluded from list A for this analysis (online supplemental table 2). Current smokers were defined in most studies as having smoked at least one cigarette per day for 6 months or more, and also included those who had stopped smoking in the last 2 years before diagnosis or interview, as recent smoking cessation could be due to early symp- toms of the disease. The cPY was calculated as follows: Σ duration (years) X average cigarette smoked per day/20 (cigarettes per pack) and was included as log(1+cPY) in the logistic regression models in order to approximate log- normal distribution.
Previous results from epidemiological studies examin- ing associations between occupational metal exposureand brain tumors are mixed. An elevated OR was ob- served among men, but not women, with occupational activities involving metals ina 6-country study of glioma risk (OR = 1.24, 95% CI 0.96–1.62) (n = 1178 cases, 1987 controls), but no association emerged when self- reports of exposure to metal or metal compounds were used . An analysis based on data from the German INTERPHONE study group, which are subsumed in the present analysis, suggested no association between hav- ing ever worked in an occupational sector involving metal production and glioma risk or according to duration of work in the sector . One U.S. studyin- cluding 489 glioma cases and 799 controls reported no overall association between occupational lead exposure as assessed using a quantitative lead exposure database and detailed job-level information , although there was some evidence of modification of the association with glioblastoma multiforme by single nucleotide poly- morphisms in genes related with oxidative stress . A positive association was observed between occupational lead exposureand brain cancer mortality in the National
Our results are based on a large population- based case-controlstudy specifically designed to assess environmental and genetic factors inprostatecancer occurrence. Cases were identified in all cancer hospitals, either public or private, that recruited prostatecancer patients in the département of Hérault. In 2011, the Hérault Cancer Registry observed 770 new cases of prostatecancerin men aged less than 75 years old. Considering that the number of cases observed in 2011 was similar during the study period, approximately 1150 new cases were expected during 2012–2013 . We identified 1098 eligible cases over the study period suggesting that the recruitment of cases in the EPICAP study was quite exhaustive, thus limiting a potential selection bias. Controls were randomly selected from the general population of the département of Hérault using quotas defined for age (5 years) and SES. The age distribution of the controls reflects the age distribution of the cases. In order to avoid selection bias, the SES distribution of the control group reflects the SES distribution of the entire département of Hérault to yield the control group similar to the general population of men of the same age in terms of SES. After the selection process, the distribution by SES between our control group and the male general population of the département of Hérault has been compared and no Table 3: Associations between height, waist circumference, waist on hip ratio andprostatecancerrisk, adjusted for body mass index
Phthalates have been widely used as plasticizers in soft plastics or in cosmetics, [ 49 ] but they have never been investigated thoroughly in relation to breast cancer incidence in an epidemiological study. We found no significant association of male breast cancer with exposure to phthalates possibly because of confounding by alkylphenolic compounds. Because of their widespread use, their effects in hormone-related cancers would deserve further attention. The role of environmental exposures to persistent organochlorine pesticides, such as DDT, was investigated in many studies with mainly negative findings [ 7 ] . Other studies in female farmers reported increased breast cancerriskin women likely exposed to pesticides, [ 11 ] or living closer to pesticide application areas. [ 12 ] Our data provide no support for an association between pesticide exposureand breast cancerin men, but the lack of information on specific pesticides may account for these negative findings.
report that the Norwegian Cancer Registry is practically complete due to mandatory reporting of cancer diagnosis, thus selection bias as it pertains to cases is likely minimal.
In 1979, Horne and Picard 102 published acase-controlstudyin the United States. The objective of the study was to investigate psychological indicators and their association with pulmonary malignancies. Physicians from two Veterans Administration Hospitals selected participants for inclusion based on chest x-ray and the presence of a visible lung lesion. In total, 44 malignant male cancer cases and 66 male controls with benign lung disease participated. Control groups were patients with X-rays showing no lung disease, including COPD. Data on job history and recent (within 5 years) life changes was collected via interview assisted with semi- structured questionnaire. Horne and Picard reported that recent significant loss statistically significantly predicted diagnosis of malignant lung cancer (p<0.001). This result should be interpreted in light of a few limitations. First, there is a possibility of information bias as a result of differential misclassification of the outcome among controls, owing to the fact that controls were hospitalized and had radiological findings consistent with lung disease; which is problematic due to the potential effect of stress on the expression of various types of disease. 81 Furthermore, there is possible confounding due to age because the median age of those with benign tumours was lower than the participants with malignant lung tumour diagnosis, and there was no adjustment for age. Finally, the results of this study may only be generalizable to male veterans, and not to the general male population.
The Montreal data collection was funded by a grant from the Canadian Institutes of Health Research (project MOP-42525) and the analysis was funded by the Guzzo- SRC Chair in Environment andCancer. Dr. Siemiatycki had salary support from the Canada Research Chair pro- gramme. Dr. Parent had salary support from the Fonds de recherche en santé du Québec. Dr. Abrahamowicz is supported by the James McGill Chair at McGill University. The Ottawa and Vancouver centres were sup- ported by a university-industry partnership grant from the Canadian Institutes of Health Research (CIHR), the latter including partial support from the Canadian Wireless Telecommunications Association. The CIHR university-industry partnerships program also includes provisions that ensure complete scientific independence of the investigators. Dr. Krewski is the Natural Sciences and Engineering Research Council of Canada Chair inRisk Science at the University of Ottawa. Coordina- tion of the INTERPHONE studyand development of the study instruments were supported by funding from the European Fifth Framework Program, “Quality of Life and Management of Living Resources” [contract QLK4- CT-1999901563] and the International Union against Cancer (UICC). The UICC received funds for this pur- pose from the Mobile Manufacturers’ Forum and GSM Association. Provision of funds to the INTERPHONE study investigators via the UICC was governed by ag- reements that guaranteed INTERPHONE's complete scientific independence. The terms of these agreements are publicly available at http://www.interphone.iarc.fr.
Prostatecancer is the most frequently diagnosed solid-tumor cancer among men in the world ( Ferlay et al., 2013 ). The only clearly established factors to date are age, a family history of the disease and ancestry. The identification of modifiable risk factors, which would be amenable to prevention, would represent a major scientific achievement. The suspicion that diet plays a role inprostatecancer development has led to the conduct of several studies on this issue. In its 2014 update on prostatecancer, the World Cancer Research Fund reported on the evidence for several dietary factors ( WCRF and AICR, 2014 ). Based on studies at the time, there was limited evidence, albeit suggestive, that high intakes of dairy products, and low plasma levels of alpha-tocopherol and selenium, are associated with increased risk of prostatecancer. For vitamin C, data were judged to be either of too low quality, too inconsistent, or the number of studies too few for conclusions to be reached. This led to the classification of vitamin C, in relation to prostatecancer, as “Limited-no conclusion.” Since then, two studies focusing on dietary supplements have been published. A Swedish case- controlstudy observed no association with use of vitamin C supplements andprostatecancer overall, or by aggressiveness ( Russnes et al., 2016 ). Moreover, ina US randomized trial, vitamin C supplementation had no effect on the risk of overall or lethal prostatecancer ( Wang et al., 2014 ).
Background and aims: Recent experimental data show that exposure to microbes during early childhood can confer immunological tolerance and protect against diseases such as Crohn’s disease (CD) (the hygiene hypothesis). Epidemiological evidence for this link however, remains controversial. Using prospective data on physician-diagnosed infections, we examined the link between this hypothesis andrisk for pediatric CD. Methods: Acase-controlstudy design was used. Pediatric CD cases (<20 yrs) were recruited from a tertiary care pediatric hospital inMontrealand population-based controls were selected using Quebec’s provincial medical insurance database and matched for age, gender, geographical location and period of insurance coverage. Exposure to infections was ascertained using prospectively recorded International Classification of Diseases -9 (ICD9) diagnostic codes. The relationship between the timing, frequency and type of infections and CD was assessed using conditional logistic regression analysis.