Validation of self-reported occupational noise exposure in participants of a French case-control study on acoustic neuroma.

OBJECTIVES: To validate self-reported occupational loud noise exposure against expert evaluation of noise levels in a French case-control study on acoustic neuroma and to estimate the impact of exposure misclassification on risk estimation. METHODS: Noise levels were evaluated in 1006 jobs held by 111 cases and 217 population controls by an expert. Case-control differences in self-reporting were analyzed with logistic models. Sensitivity, specificity, positive and negative predictive values, and observed agreement of the self-reports were computed relative to the expert evaluation. They were used to calibrate the odds ratio (OR) between lifetime ever occupational loud noise exposure and the risk of acoustic neuroma, without adjustment for measurement error of the expert assessments. RESULTS: Cases reported noise levels in individual jobs closer to the expert assessment than controls, but the case-control difference was small for lifetime exposures. For expert-rated exposure of 80 dB(A), reporting of individual jobs by cases was more sensitive (54% in cases, 37% in controls), whereas specificity (91% in cases, 93% in controls) and observed agreement (82% in cases, 81% in controls) were similar. When lifetime exposure was considered, sensitivity increased (76% in cases, 65% in controls), while cases specificity decreased (84%). When these values were used to calibrate self-reports for exposure misclassification compared to expert evaluation at 80 dB(A), the crude OR of 1.7 was reduced to 1.3. CONCLUSIONS: Despite the relatively accurate reporting of loud noise, the impact of the calibration on the OR was non-negligible.

Exposure to loud noise and risk of vestibular schwannoma: results from the INTERPHONE international case‒control study.

Objective Studies of loud noise exposure and vestibular schwannomas (VS) have shown conflicting results. The population-based INTERPHONE case‒control study was conducted in 13 countries during 2000-2004. In this paper, we report the results of analyses on the association between VS and self-reported loud noise exposure. Methods Self-reported noise exposure was analyzed in 1024 VS cases and 1984 matched controls. Life-long noise exposure was estimated through detailed questions. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using adjusted conditional logistic regression for matched sets. Results The OR for total work and leisure noise exposure was 1.6 (95% CI 1.4-1.9). OR were 1.5 (95% CI 1.3-1.9) for only occupational noise, 1.9 (95% CI 1.4-2.6) for only leisure noise and 1.7 (95% CI 1.2-2.2) for exposure in both contexts. OR increased slightly with increasing lag-time. For occupational exposures, duration, time since exposure start and a metric combining lifetime duration and weekly exposure showed significant trends of increasing risk with increasing exposure. OR did not differ markedly by source or other characteristics of noise. Conclusion The consistent associations seen are likely to reflect either recall bias or a causal association, or potentially indicate a mixture of both.

Occupational exposure to high-frequency electromagnetic fields and brain tumor risk in the INTEROCC study: An individualized assessment approach.

INTRODUCTION: In 2011, the International Agency for Research on Cancer classified radiofrequency (RF) electromagnetic fields (EMF) as possibly carcinogenic to humans (group 2B), although the epidemiological evidence for the association between occupational exposure to RF-EMF and cancer was judged to be inadequate, due in part to limitations in exposure assessment. This study examines the relation between occupational RF and intermediate frequency (IF) EMF exposure and brain tumor (glioma and meningioma) risk in the INTEROCC multinational population-based case-control study (with nearly 4000 cases and over 5000 controls), using a novel exposure assessment approach. METHODS: Individual indices of cumulative exposure to RF and IF-EMF (overall and in specific exposure time windows) were assigned to study participants using a source-exposure matrix and detailed interview data on work with or nearby EMF sources. Conditional logistic regression was used to investigate associations with glioma and meningioma risk. RESULTS: Overall, around 10% of study participants were exposed to RF while only 1% were exposed to IF-EMF. There was no clear evidence for a positive association between RF or IF-EMF and the brain tumors studied, with most results showing either no association or odds ratios (ORs) below 1.0. The largest adjusted ORs were obtained for cumulative exposure to RF magnetic fields (as A/m-years) in the highest exposed category (≥90th percentile) for the most recent exposure time window (1-4 years before the diagnosis or reference date) for both glioma, OR = 1.62 (95% confidence interval (CI): 0.86, 3.01) and meningioma (OR = 1.52, 95% CI: 0.65, 3.55). CONCLUSION: Despite the improved exposure assessment approach used in this study, no clear associations were identified. However, the results obtained for recent exposure to RF electric and magnetic fields are suggestive of a potential role in brain tumor promotion/progression and should be further investigated.

The INTEROCC case-control study: risk of meningioma and occupational exposure to selected combustion products, dusts and other chemical agents.

BACKGROUND: Little is known about occupational risk factors for meningioma. OBJECTIVES: To study whether risk of meningioma is associated with several occupational exposures, including selected combustion products, dusts and other chemical agents. METHODS: The INTEROCC study was an international case-control study of brain cancer conducted in seven countries. Data collection by interview included lifetime occupational histories. A job exposure matrix was used to derive estimates of exposure for the 12 agents. ORs for ever versus never exposed and for exposure-response using duration of exposure and cumulative exposure were derived using conditional logistic regression stratified by sex, age group, country/region, adjusted for education. RESULTS: These analyses included 1906 cases and 5565 controls. For 11 of the 12 agents, no excess risk was found for ever exposed. For ever exposure to oil mists, an elevated OR of 1.57 (95% CI 1.10 to 2.22, 51 exposed cases) was found. Statistically significant exposure-response relationships were observed with cumulative exposure (p=0.01) and duration of exposure (p=0.04). Among women, there were also significant trends for cumulative and duration of exposure to asbestos and excesses in the highest exposure categories for formaldehyde. CONCLUSIONS: Most agents examined did not provoke excess risks of meningioma. The main finding from this study is that it is the first study to identify a statistical association between exposure to oil mists and meningioma. This may be a chance finding or could be due to confounding with iron exposure and further research is required to understand whether the relationship is causal.

Occupational solvent exposure and risk of glioma in the INTEROCC study.

BACKGROUND: The aetiology of glioma remains largely unknown. Occupational solvent exposure has been suggested as a putative cause of glioma, but past studies have been inconsistent. We examined the association between a range of solvents and glioma risk within the INTEROCC project, a study of brain tumours and occupational exposures based on data from seven national case-control studies conducted in the framework of the INTERPHONE study. We also investigated associations according to tumour grade. METHODS: Data from the seven countries were standardised and then combined into one aggregate data set. Pooled odds ratios (ORs) were estimated for adjusted models that included sex, age, country-region of residence and level of educational attainment. Exposures to any solvent or 11 specific solvents or subgroups were assessed using a modified version of the FINJEM job exposure matrix (JEM) specifically developed for the study, called INTEROCC-JEM. RESULTS: Analysis included 2000 glioma cases and 5565 controls. For glioma and ever/never exposure to any solvent, the OR was 0.91 (95% confidence interval: 0.74-1.11). All ORs were <1.0 for specific solvents/subgroups. There were no increases in risk according to high or low grade of tumour. CONCLUSIONS: The results of this study show no consistent associations for any solvent exposures overall or by grade of tumour.

Lifetime occupational exposure to metals and welding fumes, and risk of glioma: a 7-country population-based case-control study.

BACKGROUND: Brain tumor etiology is poorly understood. Based on their ability to pass through the blood-brain barrier, it has been hypothesized that exposure to metals may increase the risk of brain cancer. Results from the few epidemiological studies on this issue are limited and inconsistent. METHODS: We investigated the relationship between glioma risk and occupational exposure to five metals - lead, cadmium, nickel, chromium and iron- as well as to welding fumes, using data from the seven-country INTEROCC study. A total of 1800 incident glioma cases and 5160 controls aged 30-69 years were included in the analysis. Lifetime occupational exposure to the agents was assessed using the INTEROCC JEM, a modified version of the Finnish job exposure matrix FINJEM. RESULTS: In general, cases had a slightly higher prevalence of exposure to the various metals and welding fumes than did controls, with the prevalence among ever exposed ranging between 1.7 and 2.2% for cadmium to 10.2 and 13.6% for iron among controls and cases, respectively. However, in multivariable logistic regression analyses, there was no association between ever exposure to any of the agents and risk of glioma with odds ratios (95% confidence intervals) ranging from 0.8 (0.7-1.0) for lead to 1.1 (0.7-1.6) for cadmium. Results were consistent across models considering cumulative exposure or duration, as well as in all sensitivity analyses conducted. CONCLUSIONS: Findings from this large-scale international study provide no evidence for an association between occupational exposure to any of the metals under scrutiny or welding fumes, and risk of glioma.

Interactions between occupational exposure to extremely low frequency magnetic fields and chemicals for brain tumour risk in the INTEROCC study.

OBJECTIVES: In absence of clear evidence regarding possible effects of occupational chemical exposures on brain tumour aetiology, it is worthwhile to explore the hypothesis that such exposures might act on brain tumour risk in interaction with occupational exposure to extremely low frequency magnetic fields (ELF). METHODS: INTEROCC is a seven-country (Australia, Canada, France, Germany, Israel, New Zealand and UK), population-based, case-control study, based on the larger INTERPHONE study. Incident cases of primary glioma and meningioma were ascertained from 2000 to 2004. Job titles were coded into standard international occupational classifications and estimates of ELF and chemical exposures were assigned based on job-exposure matrices. Dichotomous indicators of cumulative ELF (≥50th vs <50th percentile, 1-4 year exposure time window) and chemical exposures (ever vs never, 5-year lag) were created. Interaction was assessed on both the additive and multiplicative scales. RESULTS: A total of 1939 glioma cases, 1822 meningioma cases and 5404 controls were included in the analysis, using conditional logistic regression. There was no clear evidence for interactions between ELF and any of the chemical exposures assessed for either glioma or meningioma risk. For glioma, subjects in the low ELF/metal exposed group had a lower risk than would be predicted from marginal effects. Results were similar according to different exposure time windows, to cut-points of exposure or in exposed-only analyses. CONCLUSIONS: There was no clear evidence for interactions between occupational ELF and chemical exposures in relation to glioma or meningioma risk observed. Further research with more refined estimates of occupational exposures is recommended.

Occupational exposure to metals and risk of meningioma: a multinational case-control study.

The aim of the study was to examine associations between occupational exposure to metals and meningioma risk in the international INTEROCC study. INTEROCC is a seven-country population-based case-control study including 1906 adult meningioma cases and 5565 population controls. Incident cases were recruited between 2000 and 2004. A detailed occupational history was completed and job titles were coded into standard international occupational classifications. Estimates of mean workday exposure to individual metals and to welding fumes were assigned based on a job-exposure-matrix. Adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated using conditional logistic regression. Although more controls than cases were ever exposed to metals (14 vs. 11 %, respectively), cases had higher median cumulative exposure levels. The ORs for ever vs. never exposure to any metal and to individual metals were mostly greater than 1.0, with the strongest association for exposure to iron (OR 1.26, 95 % CI 1.0-1.58). In women, an increased OR of 1.70 (95 % CI 1.0-2.89) was seen for ever vs never exposure to iron (OR in men 1.19, 95 % CI 0.91-1.54), with positive trends in relation with both cumulative and duration of exposure. These results remained after consideration of other occupational metal or chemical co-exposures. In conclusion, an apparent positive association between occupational exposure to iron and meningioma risk was observed, particularly among women. Considering the fact that meningioma is a hormone dependent tumor, the hypothesis that an interaction between iron and estrogen metabolism may be a potential mechanism for a carcinogenic effect of iron should be further investigated.

Occupational exposure to extremely low-frequency magnetic fields and brain tumor risks in the INTEROCC study.

BACKGROUND: Occupational exposure to extremely low-frequency magnetic fields (ELF) is a suspected risk factor for brain tumors, however the literature is inconsistent. Few studies have assessed whether ELF in different time windows of exposure may be associated with specific histologic types of brain tumors. This study examines the association between ELF and brain tumors in the large-scale INTEROCC study. METHODS: Cases of adult primary glioma and meningioma were recruited in seven countries (Australia, Canada, France, Germany, Israel, New Zealand, and the United Kingdom) between 2000 and 2004. Estimates of mean workday ELF exposure based on a job exposure matrix were assigned. Estimates of cumulative exposure, average exposure, maximum exposure, and exposure duration were calculated for the lifetime, and 1 to 4, 5 to 9, and 10+ years before the diagnosis/reference date. RESULTS: There were 3,761 included brain tumor cases (1,939 glioma and 1,822 meningioma) and 5,404 population controls. There was no association between lifetime cumulative ELF exposure and glioma or meningioma risk. However, there were positive associations between cumulative ELF 1 to 4 years before the diagnosis/reference date and glioma [odds ratio (OR) ≥ 90th percentile vs. < 25th percentile, 1.67; 95% confidence interval (CI), 1.36-2.07; PLinear trend < 0.0001], and, somewhat weaker associations with meningioma (OR ≥ 90th percentile vs. < 25th percentile, 1.23; 95% CI, 0.97-1.57; PLinear trend = 0.02). CONCLUSIONS: Results showed positive associations between ELF in the recent past and glioma. IMPACT: Occupational ELF exposure may play a role in the later stages (promotion and progression) of brain tumorigenesis.

Occupational solvent exposure and risk of meningioma: results from the INTEROCC multicentre case-control study.

OBJECTIVE: To examine associations between occupational exposure to selected organic solvents and meningioma. METHODOLOGY: A multicentre case-control study conducted in seven countries, including 1906 cases and 5565 controls. Occupational exposure to selected classes of organic solvents (aliphatic and alicyclic hydrocarbons, aromatic hydrocarbons, chlorinated hydrocarbons and 'other' organic solvents) or seven specific solvents (benzene, toluene, trichloroethylene, perchloroethylene, 1,1,1-trichloroethylene, methylene chloride and gasoline) was assessed using lifetime occupational histories and a modified version of the FINJEM job-exposure matrix (INTEROCC-JEM). Study participants were classified as 'exposed' when they had worked in an occupation for at least 1 year, with a 5-year lag, in which the estimated prevalence of exposure was 25% or greater in the INTEROCC-JEM. Associations between meningioma and each of the solvent exposures were estimated using conditional logistic regression, adjusting for potential confounders. RESULTS: A total of 6.5% of study participants were ever exposed to 'any' solvent, with a somewhat greater proportion of controls (7%) ever exposed compared with cases (5%), but only one case was ever exposed to any chlorinated hydrocarbon (1,1,1-trichloroethane). No association was observed between any of the organic solvents and meningioma, in either men or women, and no dose-response relationships were observed in internal analyses using either exposure duration or cumulative exposure. DISCUSSION: We found no evidence that occupational exposure to these organic solvents is associated with meningioma.

INTEROCC case-control study: lack of association between glioma tumors and occupational exposure to selected combustion products, dusts and other chemical agents.

BACKGROUND: The aim was to investigate possible associations between glioma (an aggressive type of brain cancer) and occupational exposure to selected agents: combustion products (diesel and gasoline exhaust emissions, benzo(a)pyrene), dusts (animal dust, asbestos, crystalline silica, wood dust) and some other chemical agents (formaldehyde, oil mist, sulphur dioxide). METHODS: The INTEROCC study included cases diagnosed with glioma during 2000-2004 in sub-regions of seven countries. Population controls, selected from various sampling frames in different centers, were frequency or individually matched to cases by sex, age and center. Face-to-face interviews with the subject or a proxy respondent were conducted by trained interviewers. Detailed information was collected on socio-economic and lifestyle characteristics, medical history and work history. Occupational exposure to the 10 selected agents was assessed by a job exposure matrix (JEM) which provides estimates of the probability and level of exposure for different occupations. Using a 25% probability of exposure in a given occupation in the JEM as the threshold for considering a worker exposed, the lifetime prevalence of exposure varied from about 1% to about 15% for the different agents. Associations between glioma and each of the 10 agents were estimated by conditional logistic regression, and using three separate exposure indices: i) ever vs. never; ii) lifetime cumulative exposure; iii) total duration of exposure. RESULTS: The study sample consisted of 1,800 glioma cases and 5,160 controls. Most odds ratio estimates were close to the null value. None of the ten agents displayed a significantly increased odds ratio nor any indication of dose-response relationships with cumulative exposure or with duration of exposure. CONCLUSION: Thus, there was no evidence that these exposures influence risk of glioma.

Birth defects in the vicinity of nuclear power plants in Germany.

Living in the vicinity of nuclear power plants (NPP) is discussed here in terms of adverse health effects. A prospective population-based cohort study was conducted to evaluate whether the prevalence of birth defects in the vicinity of NPPs is elevated and scrutinize a possible distance correlation. A birth cohort born to mothers living within 10 km of two selected NPPs (study region) was compared to a region without NPP (comparison region), and an active surveillance of all live births, stillbirths, and induced abortions in the defined regions was performed. Between 01/2007 and 02/2008, all newborns were examined by specially trained study paediatricians according to the protocols of the Birth Registry Mainz Model. The cohort consisted of 5,273 infants (90% completeness). The outcome measure was an infant with birth defect(s). The prevalence of infants with birth defects was 4.5% in the study region and 4.7% in the comparison region, which corresponds to a relative risk (RR) of 0.94 (lower 95% confidence level (CL): 0.76). Thus, the prevalence of birth defects in the regions surrounding NPPs was not increased compared to those of the comparison region. Adjustment for potential confounders did not substantially change the result (RR 0.90, lower 95% CL 0.73). The adjusted and unadjusted distance approach (1/distance in km) did not show any correlation to vicinity to a NPP (p = 0.38). Specifically, within the study region, the prevalence of birth defects showed no upward trend with decreasing distance. Birth defect prevalence and most descriptive parameters in the comparison region were identical to those in the Birth Registry Mainz Model.

No association of polymorphisms in the cell polarity gene SCRIB with breast cancer risk.

The human homolog of the Drosophila Scribble (SCRIB) tumor suppressor gene encodes a protein that regulates apical-basolateral polarity in mammalian epithelia and controls cell proliferation. Due to the role of cell polarity proteins in human cancers, we investigated whether genetic variability in SCRIB impacts breast carcinogenesis and tumor pathology. Five genetic variants were analyzed for an association with breast cancer risk and histopathological tumor parameters using a single nucleotide polymorphism (SNP) tagging approach. Genotyping of five tag SNPs was performed by TaqMan allelic discrimination and RFLP-based PCR using the GENICA population-based breast cancer case-control collection including 1,021 cases and 1,015 age-matched controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by ordinal logistic regression. None of the tag SNPs was associated with breast cancer risk or tumor characteristics. Our findings suggest that genetic variability in the SCRIB polarity gene does not contribute to breast cancer development.

History of allergic disease and epilepsy and risk of glioma and meningioma (INTERPHONE study group, Germany).

The aim of the present analysis was to examine the association of a medical history of asthma, hay fever, eczema, or epilepsy with the risk of glioma and meningioma. Data of a German population-based case-control study included 381 meningioma cases, 366 glioma cases, and 1,494 controls. Participants' histories of asthma, hay fever, eczema, and epilepsy and the respective ages at onset were asked during a personal interview. A small inverse association between allergic condition and both glioma (odds ratio: 0.92; 95% CI: 0.70-1.22) and meningioma (odd ratio: 0.87; 95% CI: 0.66-1.14) was found. For glioma, this inverse association was more pronounced in persons reporting to have asthma compared to other allergic conditions. The positive association between epilepsy and particularly glioma suggests that epilepsy is an early symptom of the disease. As the association was seen also for epilepsies occurring more than a decade before the diagnosis of glioma, this might indicate either an aetiological role of epilepsy, or a relatively long preclinical phase. In conclusion our study confirms previous findings of case control studies but not those from cohort studies. However, possible selection bias in case control studies might not explain the different results in its entirety.

Validity of self-reported occupational noise exposure.

In all epidemiological studies the validity of self-reported questionnaire data is an important issue as the exposure assessment based on such data is a major source of bias in the risk estimation. A validation study was conducted based on a case-control study including 94 acoustic neuroma cases and 191 matched controls from the German Interphone Study to investigate the level of agreement between self-reported occupational noise exposure and a job-exposure-matrix (JEM) on noise exposure derived from a lifetime occupation calendar. The JEM was generated based on measurement data collected in the literature for various occupations. Level of agreement was investigated by using sensitivity, specificity, kappa coefficient and the Youden-Index. The receiver operating characteristics curve yielded an optimal cut point of 80 decibel(Acoustic) (dB(A)) to dichotomize noise exposure, displaying a moderate agreement between self-reported exposure and the JEM-based exposure (kappa of 0.53) that was slightly higher for cases than controls (kappas of 0.62 and 0.48). The agreement was only slightly lower if the longest held job or the last held job were used instead of the loudest job of the lifetime job history. The cut point of 80 dB(A) corresponds with regulations for workers safety with a recommendation to wear noise protection. The good levels of agreement between self-reported high occupational noise exposure compared with JEM-data, together with no substantial differences between cases and controls, suggest that self-reported data on occupational noise exposure is a valid exposure metric. Noise exposure appears to be appropriate if only exposure information on the last or the longest held job is available.

Medical exposure to ionising radiation and the risk of brain tumours: Interphone study group, Germany.

BACKGROUND: The role of exposure to low doses of ionising radiation in the aetiology of brain tumours has yet to be clarified. The objective of this study was to investigate the association between medically or occupationally related exposure to ionising radiation and brain tumours. METHODS: We used self-reported medical and occupational data collected during the German part of a multinational case-control study on mobile phone use and the risk of brain tumours (Interphone study) for the analyses. RESULTS: For any exposure to medical ionising radiation we found odds ratios (ORs) of 0.63 (95% confidence interval (CI)=0.48-0.83), 1.08 (95% CI=0.80-1.45) and 0.97 (95% CI=0.54-1.75) for glioma, meningioma and acoustic neuroma, respectively. Elevated ORs were found for meningioma (OR 2.32, 95% CI: 0.90-5.96) and acoustic neuroma (OR 6.45, 95% CI: 0.62-67.16) for radiotherapy to the head and neck regions. CONCLUSION: We did not find any significant increased risk of brain tumours for exposure to medical ionising radiation.

Occupational exposure to radio frequency/microwave radiation and the risk of brain tumors: Interphone Study Group, Germany.

It is still under debate whether occupational exposure to radio frequency/microwave electromagnetic fields (RF/MW-EMF) contributes to the development of brain tumors. This analysis examined the role of occupational RF/MW-EMF exposure in the risk of glioma and meningioma. A population-based, case-control study including 381 meningioma cases, 366 glioma cases, and 1,494 controls aged 30-69 years was performed in three German regions in 2000-2003. An exposure matrix for occupational activity was constructed by using information on RF/MW-EMF exposure collected in a computer-assisted personal interview. "High" exposure was defined as an occupational exposure that may exceed the RF/MW-EMF exposure limits for the general public recommended by the International Commission on Non-Ionizing Radiation Protection. Multiple conditional logistic regressions were performed separately for glioma and meningioma. No significant association between occupational exposure to RF/MW-EMF and brain tumors was found. For glioma, the adjusted odds ratio for highly exposed persons compared with persons not highly exposed was 1.21 (95% confidence interval: 0.69, 2.13); for meningioma, it was 1.34 (95% confidence interval: 0.64, 2.81). However, the slight increase in risk observed with increasing duration of exposure merits further research with larger sample sizes.

Radiofrequency electromagnetic fields emitted from base stations of DECT cordless phones and the risk of glioma and meningioma (Interphone Study Group, Germany).

The objective of this study was to test the hypothesis that exposure to continuous low-level radiofrequency electromagnetic fields (RF EMFs) increases the risk of glioma and meningioma. Participants in a population-based case-control study in Germany on the risk of brain tumors in relation to cellular phone use were 747 incident brain tumor cases between the ages of 30 and 69 years and 1494 matched controls. The exposure measure of this analysis was the location of a base station of a DECT (Digital Enhanced Cordless Telecommunications) cordless phone close to the bed, which was used as a proxy for continuous low-level exposure to RF EMFs during the night. Estimated odds ratios were 0.82 (95% confidence interval: 0.29-2.33) for glioma and 0.83 (0.29-2.36) for meningioma. There was also no increasing risk observed with duration of exposure to DECT cordless phone base stations. Although the study was limited due to the small number of exposed subjects, it is still a first indication that residential low-level exposure to RF EMFs may not pose a higher risk of brain tumors.