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Objectives: To investigate the association between occupational exposure to aromatic hydrocarbon solvents and risk of multiple myeloma (MM) in a large, consortium-based study., Methods: We pooled data on 2854 cases and 10 743 controls from nine studies participating in the InterLymph consortium. Occupational exposures to benzene, toluene and xylene were assigned by a job-exposure matrix, coupled with 'correction' of exposure probability by self-reported or expert-assessed exposure from the individual studies. Cumulative intensity was calculated as the job-specific exposure intensity multiplied by job duration, summed across jobs. Associations were estimated using logistic regression, with inclusion of covariates for study matching factors and other potential confounders. We repeated our main analysis using random-effects meta-analysis to evaluate heterogeneity of effect., Results: Benzene, toluene and xylene were each associated with MM. For the three solvents, the highest quartile of high-probability cumulative intensity exposure (vs unexposed) was associated with 42% to 63% increased risks of MM. Associations with toluene and xylene exposures were fairly consistent and robust to sensitivity analyses. The estimated effect for benzene was moderately heterogeneous between the studies. Each solvent's association with MM was stronger for exposure occurring within 20 years of diagnosis than with exposure lagged by more than 20 years., Conclusions: Our study adds important evidence for a role of aromatic hydrocarbon solvents in causation of MM. The difficulty in disentangling individual compounds in this group and a lack of data on potential carcinogenicity of toluene and xylene, in widespread current use, underscore a need for further epidemiological evaluation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Few studies have examined whether exposure to chlorinated solvents is associated with multiple myeloma. We evaluated associations between multiple myeloma and occupational exposure to six chlorinated solvents: 1,1,1-trichloroethane, trichloroethylene (TCE), methylene chloride (DCM), perchloroethylene, carbon tetrachloride and chloroform., Methods: In-person interviews obtained occupational histories and information on jobs with likely solvent exposure. We assigned exposure metrics of probability, frequency, intensity and confidence using job-exposure matrices modified by job-specific questionnaire information. We used logistic regression to estimate ORs and 95% CIs for associations between multiple myeloma and ever exposure to each, and any, chlorinated solvent and analysed whether associations varied by duration and cumulative exposure. We also considered all occupations that were given the lowest confidence scores as unexposed and repeated all analyses., Results: Risk of multiple myeloma was elevated for subjects ever exposed to 1,1,1-trichloroethane (OR (95% CI): 1.8 (1.1 to 2.9)). Ever exposure to TCE or DCM also entailed elevated, but not statistically significant, risks of multiple myeloma; these became statistically significant when occupations with low confidence scores were considered unexposed (TCE: 1.7 (1.0 to 2.7); DCM: 2.0 (1.2 to 3.2)). Increasing cumulative exposure to perchloroethylene was also associated with increasing multiple myeloma risk. We observed non-significantly increased multiple myeloma risks with exposure to chloroform; however, few subjects were exposed., Conclusions: Evidence from this relatively large case-control study suggests that exposures to certain chlorinated solvents may be associated with increased incidence of multiple myeloma; however, the study is limited by relatively low participation (52%) among controls.

Recombinant human parathyroid hormone (1-34) (rhPTH 1-34), teriparatide (Forsteo in Europe), is a new compound that has been introduced and shown to be successful in the treatment of osteoporosis. The mechanisms of action include a pulsative influence on the RANKL/OPG system resulting in osteoblast activation and increased bone formation by teriparatide. In malignant myeloma there is an imbalance between osteoclast and osteoblast activity with involvement of the RANKL/OPG system among others. We report a case with monoclonal gammopathy of uncertain significance (MGUS) who developed malignant myeloma after teriparatide treatment and we suggest that in addition to malignant myeloma and smouldering myeloma, MGUS should also be considered contraindicated for teriparatide treatment.

Objectives: Investigating the relationship between occupational exposure to pesticides and the risk of lymphoid neoplasms (LNs) in men., Methods: A hospital-based case-control study was conducted in six centres in France between 2000 and 2004. The cases were incident cases with a diagnosis of LN aged 18-75 years. During the same period, controls of the same age and sex as the cases were recruited in the same hospital, mainly in the orthopaedic and rheumatological departments. Exposures to pesticides were evaluated through specific interviews and case-by-case expert reviews. Four hundred and ninety-one cases (244 cases of non-Hodgkin's lymphoma (NHL), 87 of Hodgkin's lymphoma (HL), 104 of lymphoproliferative syndromes (LPSs) and 56 of multiple myeloma (MM) cases) and 456 controls were included in the analyses. The odds ratios (ORs) and 95% CI were estimated using unconditional logistic regressions., Results: Positive associations between HL and occupational exposure to triazole fungicides and urea herbicides were observed (OR = 8.4 (2.2 to 32.4), 10.8 (2.4 to 48.1), respectively). Exposure to insecticides, fungicides and herbicides were linked to a threefold increase in MM risk (OR = 2.8 (1.2 to 6.5), 3.2 (1.4 to 7.2), 2.9 (1.3 to 6.5)). For LPS subtypes, associations restricted to hairy-cell leukaemia (HCL) were evidenced for exposure to organochlorine insecticides, phenoxy herbicides and triazine herbicides (OR = 4.9 (1.1 to 21.2), 4.1 (1.1 to 15.5), 5.1 (1.4 to 19.3)), although based on small numbers. Lastly, despite the increased ORs for organochlorine and organophosphate insecticides, carbamate fungicides and triazine herbicides, no significant associations were evidenced for NHL., Conclusions: The results, based on case-by-case expert review of occupation-specific questionnaires, support the hypothesis that occupational pesticide exposures may be involved in HL, MM and HCL and do not rule out a role in NHL. The analyses identified specific pesticides that deserve further investigation and the findings were consistent with those of previous studies.

Objective: To evaluate the association between personal hair dye use and risk of multiple myeloma among women., Methods: A population-based case-control study of 175 cases of multiple myeloma and 679 controls. Cases and controls were interviewed regarding the type and colour of hair colouring product used, age at first use, age use stopped, duration, and the frequency of use per year. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using unconditional logistic regression to compare never users with four exposure groups: all users, ever semi-permanent dye users, ever permanent dye users and dark permanent dye users (most frequent use)., Results: No association was found between ever reporting hair colouring product use and myeloma risk among all users (OR 0.8; 95% CI 0.5 to 1.1), semi-permanent dye users (OR 0.7; 95% CI 0.4 to 1.2), permanent dye users (OR 0.8; 95% CI 0.5 to 1.1) or dark permanent dye users (OR 0.8; 95% CI 0.5 to 1.3). There were no significant associations among women who used hair dyes before 30 years of age, started use before 1980, had >or=240 lifetime applications, or had used dark permanent dye for 28 or more years., Conclusion: No evidence of an association between hair colouring product use and myeloma risk was found. However, given the conflicting body of literature on hair colouring product use and risk of multiple myeloma, this question should be further evaluated in larger studies or consortia, and in high risk groups.

Objectives: This nested case-control study was based on data in a cohort study of more than 18,000 petroleum distribution workers exposed to gasoline, which contains about 2%-3% benzene. Risks of leukaemia, acute myeloid leukaemia, multiple myeloma, and kidney cancer were examined relative to exposure to gasoline., Methods: For each case, up to five individually matched controls were selected. Analyses based on the Mantel-Haenszel procedure as well as univariate and multivariate conditional logistic regression were performed for each disease category. Jobs with similar exposures were grouped into homogeneous categories for analysis. Several quantitative indices of exposure to gasoline were used in the analyses: duration of exposure, cumulative exposure, frequency of peak exposure, and time of first exposure., Results: No increased risks for the four cancers were found for any job category. Analyses with logistic regression models based on duration of exposure, cumulative exposure, and frequency of peak exposure did not show any increased risk or exposure-effect relation. Time of first exposure to gasoline was also found to be unrelated to the four diseases under investigation., Conclusion: Exposure to gasoline or benzene at the concentrations experienced by this cohort of distribution workers is not a risk factor for leukaemia (all cell types), acute myeloid leukaemia, multiple myeloma, or kidney cancer.

Objective: To evaluate the relation between mortality from lymphohaematopoietic cancer and long term, low level exposures to benzene among male petroleum distribution workers., Methods: This nested case control study identified all fatal cases of lymphohaematopoietic cancer among a previously studied cohort. Of the 29 cases, 14 had leukaemia, seven multiple myeloma, and eight non-Hodgkin's lymphoma. A four to one matching ratio was used to select a stratified sample of controls from the same cohort, controlling for year of birth and time at risk. Industrial hygienists estimated workplace exposures for benzene and total hydrocarbons, without knowledge of case or control status, for combinations of job, location, and era represented in all work histories. Average daily benzene concentrations ranged from 0.01 to 6.2 parts per million (ppm) for all jobs. Company medical records were used to abstract information on other potential confounders such as cigarette smoking, although the data were incomplete. Odds ratios (ORs) were calculated with conditional logistic regression techniques for several exposure variables., Results: Risks of leukaemia, non-Hodgkin's lymphoma, and multiple myeloma were not associated with increasing cumulative exposure to benzene or total hydrocarbons. For leukaemia, the logistic regression model predicted an OR of 1.002 (P < 0.77) for each ppm-y of exposure to benzene. Duration of exposure to benzene was more closely associated with risk of leukaemia than other exposure variables. It was not possible to completely control for other risk factors, although there was suggestive evidence that smoking and a family history of cancer may have played a part in the risk of leukaemia., Conclusion: This study did not show a relation between lymphohaematopoietic cancer and long term, low level exposures to benzene. The power of the study to detect low-such as twofold-risks was limited. Thus, further study on exposures to benzene in this concentration range are warranted.

Objective: To determine the risk of developing acute myeloid leukaemia (AML) and multiple myeloma in a cohort of workers exposed to benzene. The results were used to show the importance of taking specificity of disease into consideration in causation analysis., Methods: Data were derived from a cohort of workers employed at two Goodyear plants in Ohio in the manufacture of Pliofilm. Based on data in the Pliofilm study, several papers that examined the relation between exposure to benzene and leukaemia (all cell types combined) have been published. In the current analyses based on updated data in the study, standardised mortality ratios (SMRs) and 95% confidence intervals (95% CIs) were calculated for AML and multiple myeloma by cumulative exposure to benzene. The results based on AML were compared with those for leukaemia (all cell types combined) published previously., Results: An exposure response relation was shown between cumulative exposure to benzene and AML. No increased risk of AML was detected for cumulative exposure to benzene below 200 ppm-years (SMR 0.91). Above 200 ppm-years, risk of AML rose drastically; reaching a significant SMR of 98.37 for > 400 ppm-years. For multiple myeloma, no relation with exposure to benzene was detected., Conclusion: Analysis specific to AML shows the importance of taking specificity of disease into consideration in causation analysis. This investigation shows that previous analyses based on all leukaemia cell types combined have incorrectly set the estimated threshold too low, and have underestimated risk above the threshold. Current regulatory policies that rely on previous analyses based on all leukaemia cell types combined should be re-examined.