Occupational solar exposure and basal cell carcinoma. A review of the epidemiologic literature with meta-analysis focusing on particular methodological aspects.

BACKGROUND: Numerous epidemiologic studies and a few systematic reviews have investigated the association between occupational solar exposure and basal cell carcinoma (BCC). However, previous reviews have several deficits with regard to included and excluded studies/risk estimates and the assessment of risk of selection bias (RoSB). Our aim was to review epidemiologic studies with a focus on these deficits and to use meta-(regression) analyses to summarize risk estimates. METHODS: We systematically searched PubMed (including MEDLINE) and Embase for epidemiologic studies. Study evaluation considered four main aspects of risk of bias assessments, i.e. Selection of subjects (selection bias); Exposure variables; Outcome variables; Data analysis. RESULTS: Of 56 identified references, 32 were used for meta-(regression) analyses. The overall pooled risk estimate for BCC comparing high/present vs. low/absent occupational solar exposure was 1.20 (95% CI 1.02-1.43); among studies without major deficits regarding data analysis, it was 1.10 (95% CI 0.91-1.33). Studies with low and high RoSB had pooled risk estimates of 0.83 (95% CI 0.73-0.93) and 1.95 (95% CI 1.42-2.67), respectively. The definitions of exposure and outcome variables were not correlated with study risk estimates. Studies with low RoSB in populations with the same latitude or lower than Germany had a pooled risk estimate of 1.01 (95% CI 0.88-1.15). CONCLUSION: Due to the different associations between occupational solar exposure and BCC among studies with low and high RoSB, we reason that the current epidemiologic evidence base does not permit the conclusion that regular outdoor workers have an increased risk of BCC.

Estimation of an Exposure Threshold Value for Compensation of Silica-Induced COPD Based on Longitudinal Changes in Pulmonary Function.

(1) Background: To estimate the cumulative exposure to respirable crystalline silica (RCS) that reduces lung function to an extent corresponding with airway obstruction equivalent to chronic obstructive pulmonary disease (COPD). (2) Methods: The study is based on a miners' cohort with longitudinal data on lung function and RCS exposure. Random-effects linear regression models, allowing for a possible threshold concerning the exposure concentration were used to analyze the impact of RCS on the ratio of forced expiratory volume in 1 s and forced vital capacity (FEV1/FVC). The proposed threshold is the amount of RCS resulting in a decrease in FEV1/FVC from the expected value to the lower limit of normal. (3) Results: The analysis shows that a threshold model fits the data significantly better than the usual linear model. The estimated threshold value for the exposure concentration is 0.089 mg/m3. Using this threshold, the estimate for the corresponding reference dose for RCS is 2.33 mg/m3·y. (4) Conclusions: The analysis confirmed that RCS has a negative impact on lung function. The effect is primarily due to exposure above a concentration threshold of 0.1 mg/m3. It is recommended that COPD should be compensated as an occupational disease if cumulative exposure was at least 2 mg/m3·y above this threshold.

Effects of occupational exposure to respirable quartz dust on acute myocardial infarction.

OBJECTIVES: The aim of this study is to investigate the effects of occupational exposure to respirable quartz (RQ) on first acute myocardial infarction (AMI). RQ causes pulmonary diseases like silicosis and has also been linked to cardiovascular diseases. Inflammation is hypothesised as the underlying pathway. METHODS: We performed a 1:3 matched case-control study nested in a cohort of male uranium miners. We included cases (identified from hospital records and validated according to WHO criteria) who had suffered their first AMI while still employed and <65 years of age. Controls were matched by date of birth and Wismut recruitment era. RQ exposure was derived from a job-exposure matrix. We performed a conditional logistic regression adjusted for smoking, metabolic syndrome and baseline erythrocyte sedimentation rate. Subgroups by date of birth and Wismut recruitment era were analysed to minimise the impact of pre-exposures. RESULTS: The study base comprised 292 matched sets. The cumulative exposure ranged from 0 to 38.9 mg/m3-years RQ. The adjusted OR of the highest RQ tertile (>14.62 mg/m3-years) was 1.27 (95% CI 0.82 to 1.98). However, for miners born after 1928 and hired in the earliest recruitment era (1946-1954), a significantly elevated risk was seen in the highest RQ tertile (OR=6.47 [95% CI 1.33 to 31.5]; 50 matched sets). CONCLUSIONS: An impact of quartz dust on first AMI was observed only in a small subgroup that had virtually no pre-exposure to RQ. Further studies on the basis of complete occupational history are required to substantiate this finding.

New insights into the mortality risk from nasopharyngeal cancer in the national cancer institute formaldehyde worker cohort study.

BACKGROUND: Indications were found that a diagnostic bias could have contributed to the National Cancer Institute's (NCI) suggestion of a persistent increased mortality risk for nasopharyngeal cancer (NPC). METHODS: NCI provided the cohort data updated through 2004. We computed local county rate-based standardized mortality ratios (SMRs) for NPC and all other entities of the pharynx for two time periods. Moreover, SMRs were calculated for pharyngeal cancer in relation to study site by cumulative exposure to formaldehyde (FA). RESULTS: Overall, our results corroborate the indications of a diagnostic bias by strong but contrary temporal trends for NPC and pharynx, not specified. Moreover, it was shown that mortality risks were increased in the Wallingford cohort for all pharyngeal cancer combined and for pharyngeal cancer excluding NPC. In contrast, no increased risks for these categories were found in the nine other study sites combined. CONCLUSIONS: Our re-analysis provided little or no evidence to support NCI's suggestion of a persistent association between FA exposure and mortality from NPC.

The Diesel Exhaust in Miners Study provides no evidence for an increase in risk for lung cancer in miners exposed to diesel engine emissions.

The Diesel Exhaust in Miners Study is unquestionably the most suitable data material to date to examine a possible link between diesel engine emissions and lung cancer risk. But the results do not appear to be consistent in themselves. The crucial methodological problem in this study, however, has yet to be discovered, to which the lack of any description of age related information (year of birth, year of hire, year of first exposure, year of death) for the cohort as well as for the cases might have contributed. This information is important to understand the flaws in the analysis. It turns out that the year of birth is associated with the exposure, i.e. with the chance to be exposed over a certain period of time as well as with the chance to be an ever-smoker. A further important issue for the interpretation of the results is the validity of the data on smoking, which are mainly obtained from next of kin for decedents up to 50 years after death. Taking all these aspects into account, it can be concluded that only the SMR-analysis can be considered from all published results.

Occupational exposure to respirable crystalline silica and chronic non-malignant renal disease: systematic review and meta-analysis.

BACKGROUND: While occupational exposure to respirable silica is known to lead to lung disease, most notably silicosis, its association with chronic kidney disease is unclear. OBJECTIVES: This review explores the association between occupational exposure to respirable silica and chronic non-malignant renal disease such as glomerulonephritis. The evidence has been collected and compiled. Possible sources of bias are thoroughly discussed. METHODS: Cohort studies with silica exposure and case-control studies of renal disease were searched in PubMed until January 2015. Two authors independently abstracted data; any disagreement was resolved by consulting a third reviewer. A meta-analysis was performed to evaluate the association to silica exposure. RESULTS: A total of 23 cohort and four case-control studies were included in the analysis. The meta-analysis of cohort studies yielded elevated overall SMRs for renal disease. Some studies, however, included dose-response analyses, most of which did not show a positive trend. The approaches and results of the case-control studies were very heterogeneous. CONCLUSIONS: While the studies of cohorts exposed to silica found elevated SMRs for renal disease, no clear evidence of a dose-response relationship emerged. The elevated risk may be attributed to diagnostic and methodological issues. In order to permit a reliable estimation of a possible causal link, exposed cohorts should be monitored for renal disease, as the information from mortality studies is hardly reliable in this field.

A critical review of the relationship between occupational exposure to diesel emissions and lung cancer risk.

In 2012, a working group of the International Agency for Research on Cancer classified diesel exhaust (DE) as a human carcinogen (Group 1). This decision was primarily based on the findings of the Diesel Exhaust in Miners Study (DEMS). The disparity between the results of various methodological approaches applied to the DEMS led to several critical commentaries. An expert panel was subsequently set up by the Health Effects Institute to evaluate the DEMS results, together with a large study in the trucking industry. The panel concluded that both studies provided a useful basis for quantitative risk assessments (QRAs) of DE exposure. However, the results of both studies were non-definitive as the studies suffer from several methodological shortcomings. We conducted a critical review of the studies used by the International Agency for Research on Cancer (IARC) working group to evaluate the relationship between DE and lung cancer. The aim was to assess whether the available studies support the statement of a causal relationship and, secondarily if they could be used for QRA. Our review highlights several methodological flaws in the studies, amongst them overadjustment bias, selection bias, and confounding bias. The conclusion from our review is that the currently published studies provide little evidence for a definite causal link between DE exposure and lung cancer risk. Based on two studies in miners, the DEMS and the German Potash Miners study, QRA may be conducted. However, the DEMS data should be reanalyzed in advance to avoid bias that affects the presently published risk estimates.

A diagnostic bias might be a much simpler explanation for the apparently elevated risk for nasopharyngeal cancer with respect to formaldehyde.

In 2009, a working group of the International Agency for Research on Cancer classified formaldehyde as carcinogenic to humans (Group 1) and concluded that formaldehyde causes cancer of the nasopharynx (NPC) and leukemia. The results of a large cohort study of industrial workers exposed to formaldehyde, conducted by the U.S. National Cancer Institute, mainly contributed to the available body of epidemiologic evidence. In their recent updated re-analysis of these cohort data published in your journal, Dr Marsh and his colleagues concluded that the results of the original analysis of NPC-risk are misleading because they are based on inappropriate regression analyses. In our view the reason for the elevated NPC risk reported in the original analysis might be also another one - a diagnostic bias. Therefore, it would be very helpful if the authors provided results for all other sub-categories (as three-digit categories of the International Classification of Diseases) of the pharynx to verify the hypothesis described and, hence, to clarify the relationship between exposure to formaldehyde and the risk of NPC.

An approach to adjust standardized mortality ratios for competing cause of death in cohort studies.

PURPOSE: The calculation of standardized mortality ratios (SMRs) is a standard tool for the estimation of health risks in occupational epidemiology. An increasing number of studies deal with the analysis of the mortality in employees suffering from an occupational disease like silicosis or coal-worker pneumoconiosis (CWP). Their focus lies not on the mortality risk due to the occupational disease itself, but on other diseases such as lung cancer or heart diseases. Using population-based reference rates in these studies can cause misleading results because mortality rates of the general population do not reflect the elevated mortality due to the occupational disease investigated. Hence, the purpose of the present paper is to develop an approach to adjust the risk estimates for other causes of death with respect to the effect of an occupational disease as a competing cause of death in occupational mortality cohort studies. METHODS: To overcome the problems associated with SMRs, the paper makes use of proportional mortality ratios (PMR), which are a further approach for the estimation of health risks in occupational epidemiology. The cause-specific SMR can be rewritten as a product of PMR times the overall SMR. The PMR can be adjusted by ignoring the competing cause of death. Hence, an adjusted cause-specific SMR can be derived by multiplying this adjusted PMR with the overall SMR. This approach is applied to studies concerning lung cancer risk in coal miners suffering from CWP. RESULTS AND CONCLUSIONS: The usual approach for calculating SMRs leads to an underestimation of the real lung cancer risk in subgroups of miners suffering from CWP. The same effect can be observed in workers exposed to respirable silica already suffering from silicosis. The presented approach results in more realistic risk estimation in mortality cohort studies of employees suffering from an occupational disease. It is easily calculable on the basis of usually published values of observed cases and the corresponding cause-specific SMR.

Dinitrotoluene exposure in the copper mining industry and renal cancer: a case-cohort study.

OBJECTIVES: To evaluate the association between dinitrotoluene (DNT) exposure and renal cancer in a case-cohort study. METHODS: This case-cohort study was conducted among men born between 1920 and 1974 (n=16 441) who were gainfully employed between 1953 and 1990 in one of two copper mines in Mansfeld, Saxony-Anhalt, former German Democratic Republic, and followed up till 31 December 2006. The study included 109 cases with renal cancer identified by record linkage with the Common Cancer Registry of the New Federal States of Germany (GKR) or by a network of pathology institutes. A comparison subcohort of 999 cohort members was selected at random from the total cohort. Duration and intensity of inhalation and dermal exposure to DNT were assessed on the basis of a job exposure matrix. A time-dependent Cox proportional hazards model modified for case-cohort design was used to assess the relationship between cumulative inhalation and dermal DNT exposure and renal cancer. RESULTS: Elevated risks were found for medium (HR=2.73; 95% CI 1.00 to 7.42) and high (HR=1.81; 95% CI 0.75 to 4.33) dermal exposure to DNT. Relative risks for medium inhalation exposure to DNT were not increased (HR=0.93; 95% CI 0.48 to 1.79) while relative risks for high inhalation exposure to DNT were elevated to 1.36 (95% CI 0.84 to 2.21). We found a statistically significant HR of 2.12 (95% CI 1.03 to 4.37) for combined medium or high inhalation and medium or high dermal exposure to DNT. CONCLUSIONS: According to our case-cohort study, dermal and inhalation exposure to DNT is associated with increased renal cancer risk.