Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exposure to benzene is generally accepted as a cause of acute myeloid leukemia (AML), but the association with other cell types of leukemia and other lymphatic and hematopoietic cancers is controversial. We compiled epidemiologic research on benzene and lymphatic and hematopoietic cancers in order to assess the pattern of associations. Eighteen relevant community-based and 16 industry-based studies were located. Four of seven studies of lymphatic and hematopoietic cancer in the aggregate identified relative risks of 1.8 or more, and eight of 14 total leukemia studies yielded relative risks in that range. The few available studies of specific histologic types of leukemia do not indicate larger or more consistent elevations in risk for AML compared to other leukemia cell types. Sporadic reports have linked benzene to non-Hodgkin's lymphoma and multiple myeloma, but most studies do not indicate a positive association. Limitations in study quality, particularly exposure assessment, pervade all of the studies reviewed, and the distinction between studies addressing benzene and those addressing jobs in industries that use benzene is somewhat arbitrary. Nonetheless, the epidemiologic evidence linking benzene to leukemia in the aggregate, as well as for subtypes other than AML, is no less persuasive than that for AML alone.
 ...
PMID:Review of epidemiologic evidence on benzene and lymphatic and hematopoietic cancers. 905 51

We updated a cohort mortality study of 4,172 workers at a chemical plant to examine cancer mortality among workers exposed to low levels of benzene. Overall mortality [standardized mortality ratio (SMR) = 1.0; 95% confidence interval (CI) = 0.9-1.1] and cancer mortality (SMR = 1.0; 95% CI = 0.8-1.3) rates were at expected levels for production workers with benzene exposure. We observed elevated, albeit imprecise, rates of leukemia (SMR = 2.3; 95% CI = 0.7-5.3) and multiple myeloma (SMR = 2.3; 95% CI = 0.7-9.4) in this group of workers. The leukemias and multiple myelomas occurred predominantly among workers 20 or more years after first exposure. The leukemias were not restricted to acute myelogenous subtypes, and they occurred predominantly among workers hired before 1950 at exposure levels lower than previously reported. Leukemia (SMR = 1.3; 95% CI = 0.6-2.4) and multiple myeloma (SMR = 1.2; 95% CI = 0.3-2.9) rates were at expected levels among maintenance workers with intermittent high exposure to benzene. These findings provide evidence on both sides of the debate about whether low benzene exposure increases the risk of multiple myeloma and all types of leukemia.
 ...
PMID:Cancer mortality among workers with benzene exposure. 911 30

Two case series and two epidemiological studies in the 1970s and 1980s suggested that benzene exposure might be a risk factor for multiple myeloma. An analysis has now been conducted of the published population-based and hospital-based case-control studies published through mid-1995 that permit examination of the relationship between multiple myeloma and benzene exposure or surrogates for benzene exposure. No increased association was found between multiple myeloma and benzene exposure or exposure to chemical groups that included benzene. The odds ratios from these analyses approximated 1.0. Exposures to petroleum products and employment in petroleum-related occupations did not appear to be risk factors for multiple myeloma. Cigarette smoking, as a surrogate of benzene exposure, was not found to be associated with myeloma, while some studies of products of combustion described as "engine exhaust" did show a significant association with multiple myeloma. In toto, the population-based and hospital-based case-control literature indicated that benzene exposure was not a likely causal factor for multiple myeloma.
 ...
PMID:Does benzene cause multiple myeloma? An analysis of the published case-control literature. 911 25

A reanalysis of the Pliofilm cohort was conducted incorporating six additional years of follow-up information gathered by the National Institute of Occupational Safety and Health (NIOSH) and a new set of exposure estimates developed recently. The distribution of individual worker exposures calculated with the Paustenbach exposure estimates was compared to those derived using two earlier sets of job-, plant-, and year-specific exposure estimates. A traditional standardized mortality ratio analysis and the Cox proportional hazards model were used to investigate the impact of these exposure estimates and the NIOSH updated information on evaluation of benzene's leukemogenicity. There were no additional cases of multiple myeloma or any indication of increased incidences of solid tumors. The data added in the update did not greatly modify the estimated relative risk of all leukemias associated with benzene exposure but confirmed previous findings that occupational exposure only to very high concentrations had leukemogenic potential. Leukemia has not been observed in anyone who began employment in Pliofilm production after 1950. Neither the Paustenbach nor the Crump exposures gave dose-response estimates as steep as that resulting from the Rinsky exposures.
 ...
PMID:Leukemia risk associated with benzene exposure in the Pliofilm cohort. 911 29

Case reports have suggested an association between benzene exposure and multiple myeloma. Because petroleum workers are exposed to benzene or benzene-containing liquids, studies of these workers provide an opportunity for investigating the relationship between benzene and multiple myeloma. A large number of cohort studies of petroleum workers have been conducted. However, few of them have reported results of multiple myeloma separately. One reason is that multiple myeloma is usually grouped with other lymphopoietic cancers in the analysis. Another reason is that multiple myeloma is relatively rare, and few individual studies are large enough to provide reliable risk estimates. To determine the risk of multiple myeloma in petroleum (refinery, distribution, production, and pipeline) workers, we have identified 22 cohort mortality studies of petroleum workers in the United States, the United Kingdom, Canada, and Australia. Authors of these studies were contacted, and data on the number of observed deaths and age-specific person-years of observation were requested. Data from individual studies were combined in a pooled analysis (meta-analysis). In addition to the pooled analyses, results for individual cohorts, most of which have never been reported before, are also presented. The combined multinational cohort consisted of more than 250,000 petroleum workers, and the observation period covered an interval of 55 years from 1937 to 1991. A total of 205 deaths from multiple myeloma were observed, compared to 220.93 expected, a total derived from respective national mortality rates. The corresponding standardized mortality ratio (SMR) was 0.93 and the 95% confidence interval (95% CI) was 0.81-1.07. Additional analyses were performed by type of facility and industrial process. Stratum-specific SMRs (95% CIs) were 0.92 (0.77-1.09) for refinery workers and 0.93 (0.69-1.23) for distribution workers. When individual cohorts were stratified by length of observation, no pattern was detected. The pooled analysis indicates that petroleum workers are not at an increased risk of multiple myeloma as a result of their exposure to benzene, benzene-containing liquids, or other petroleum products in their work environment. This conclusion is supported by cohort studies of workers in other industries who were exposed to benzene as well as by population-based case-control studies of multiple myeloma and occupational exposures.
 ...
PMID:Multiple myeloma and benzene exposure in a multinational cohort of more than 250,000 petroleum workers. 935 82

Epidemiologic evidence on the relationship between organic solvents and cancer is reviewed. In the 1980s, more than a million persons were potentially exposed to some specific solvents in the United States; in Canada, 40 percent of male cancer patients in Montreal had experienced exposure to solvents; in the Finnish population, one percent was regularly exposed. There is evidence for increased risks of cancer following exposure to: trichloroethylene (for the liver and biliary tract and for non-Hodgkin's lymphomas); tetrachloroethylene (for the esophagus and cervix--although confounding by smoking, alcohol, and sexual habits cannot be excluded--and non-Hodgkin's lymphoma); and carbon tetrachloride (lymphohematopoietic malignancies). An excess risk of liver and biliary tract cancers was suggested in the cohort with the high exposure to methylene chloride, but not found in the other cohorts where an excess risk of pancreatic cancer was suggested. 1,1,1-trichloroethane has been used widely, but only a few studies have been done suggesting a risk of multiple myeloma. A causal association between exposure to benzene and an increased risk of leukemia is well-established, as well as a suggested risk of lung and nasopharynx cancer in a Chinese cohort. Increased risks of various gastrointestinal cancers have been suggested following exposure to toluene. Two informative studies indicated an increased risk of lung cancer, not supported by other studies. Increased risks of lymphohematopoietic malignancies have been reported in some studies of persons exposed to toluene or xylene, but not in the two most informative studies on toluene. Occupation as a painter has consistently been associated with a 40 percent increased risk of lung cancer. (With the mixed exposures, however, it is not possible to identify the specific causative agent[s].) A large number of studies of workers exposed to styrene have evidenced no consistent excess risk of all lymphohematopoietic malignancies, although the most sensitive study suggested an excess risk of leukemia among workers with a high exposure.
 ...
PMID:Organic solvents and cancer. 949 2

Epidemiologic studies have suggested that benzene exposure may be a risk factor of multiple myeloma (MM). We performed meta-analyses of case-control studies to assess the association between occupational exposure to benzene and the risk of MM. We divided the occupational sources of benzene exposure into 4 categories, benzene and/or organic solvents, petroleum, petroleum products, and engine exhaust, for conducting the meta-analysis. As a result, a significant positive association was indicated between exposure to engine exhaust and MM (summary odds ratio or summary OR=1.34, 95% confidence interval or 95%CI=1.14-1.57). However, no significant associations were obtained for benzene and/or organic solvents (summary OR=0.74, 95%CI=0.60-0.90), petroleum (summary OR=1.11, 95%CI=0.96-1.28) and petroleum products (summary OR=1.08, 95%CI=0.89-1.33) with risk of MM. These results suggested that benzene exposure itself was not likely to be a risk factor of MM. It is thought that several harmful chemical agents in engine exhaust, other than benzene, could be etiologically related to the risk of MM. Further case-control studies on MM are needed to obtain more information about detailed occupational exposure to toxic substances.
 ...
PMID:Meta-analysis of multiple myeloma and benzene exposure. 1176 42

Bendamustine hydrochloride is the active ingredient of Ribomustin (Ribosepharm GmbH, Munich, Germany). It was first synthesized in 1963 in the German Democratic Republic. Bendamustine is chemically related to the alkylating agent chlorambucil, with the benzene ring in the chlorambucil molecule replaced by a 1-methyl-benzimidazole moiety. The mechanisms of action of bendamustine have been under investigation since the early 1960s, and its first use was as a treatment for multiple myeloma in 1969. Bendamustine has three active moieties: an alkylating group, in common with the nitrogen mustard family; a benzimidazole ring, which may act as a purine analog; and a butyric acid side-chain. Bendamustine undergoes extensive first-pass metabolism. However, unmetabolized bendamustine accounts for about 45% of the total drug recovered in urine. The main transformation product is a cytotoxic hydroxy metabolite (beta-hydroxybendamustine). Bendamustine was originally synthesized with the intention of producing an antineoplastic agent with low toxicity and both alkylating and antimetabolic properties. However, it has been shown that, at least at high concentrations, it acts primarily as an alkylating agent. Based on the multiple actions and cell cycle effects of this agent, mechanism-based combination strategies have been suggested. The rationales behind bendamustine combination regimens and the importance of the sequence of administration of different drugs are explored.
 ...
PMID:Metabolism and mechanisms of action of bendamustine: rationales for combination therapies. 1217 Apr 25

Lymphohaematopoeitic cancer mortality was examined among 4417 workers at a chemical plant by cumulative and peak benzene exposure. There was little evidence of increasing risk with increasing cumulative exposure for all leukaemias or acute non-lymphocytic leukaemias (ANL), or the other lymphohaematopoeitic cancers with the exception of multiple myeloma. For multiple myeloma, the SMRs were 1.1 (95% CI 0.3 to 2.5) in the non-exposed group, 1.4 (95% CI 0.2 to 5.1) in the <1 ppm-years, 1.5 (95% CI 0.2 to 5.4) in the 1-6 ppm-years, and 2.6 (95% CI 0.7 to 6.7) in the >6 ppm-years group. We found no trends by peak exposures for any of the cancers. However, when peak exposures over 100 ppm for 40 or more days were considered, the observed number of all leukaemias (SMR = 2.7, 95% CI 0.8 to 6.4), ANL (SMR = 4.1, 95% CI 0.5 to 14.9), and multiple myeloma (SMR = 4.0, 95% CI 0.8 to 11.7) were greater than expected. While the observed number of deaths is small in this study, the number of peak exposures greater than 100 ppm to benzene is a better predictor of risk than cumulative exposure. The dose rate of benzene and a threshold for exposure response may be important factors for evaluating lymphohaematopoietic risk.
 ...
PMID:Lymphohaematopoeitic cancer mortality among workers with benzene exposure. 1293 90

In certain countries outside of the United States, benzene remains a significant occupational hazard. This article provides a brief historical perspective of benzene use and general aspects of benzene toxicology, focusing primarily on benzene-induced hematotoxicity and leukemogenesis. Although the causal relationship between benzene and acute myelogenous leukemia is unequivocal, there has been considerable debate regarding the potential role of benzene exposure in the development of other hematopoietic malignancies, including chronic myelogenous leukemia, chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and multiple myeloma. The relationship between benzene and these other diseases also is discussed briefly.
 ...
PMID:Benzene and hematopoietic malignancies. 1532 20


<< Previous 1 2 3 4 5 Next >>