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      Work-related leukemia: a systematic review

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          Abstract

          Leukemia is a complex disease, which only became better understood during the last decades following the development of new laboratory techniques and diagnostic methods. Despite our improved understanding of the physiology of the disease, little is yet known about the causes of leukemia. A variety of potential risk factors have been suggested so far, including personal habits and lifestyle, and a wide range of occupational or environmental exposures. A causal association with leukemia has only been documented to date for ionizing radiation, benzene and treatment with cytostatic drugs, but there is an ongoing scientific debate on the possible association of leukemia with a number of other work-related hazards. In this article, we have reviewed scientific studies, published over the past 5 years, which investigated potential associations between leukemia and exposure to occupational risk factors. The systematic literature review took place via electronic databases, using specific search criteria, and independent reviewers have further filtered the search results to identify the number of articles, presented in our paper. A large number of studies included in the review referred to the effects of ionizing radiation, where new data suggest that the effects of exposure to small doses of ionizing radiation should probably be reevaluated. Some other works appear to substantiate a potential association of the disease with certain pesticides. Further research is also suggested regarding the role of infectious agents or exposure to certain chemicals like formaldehyde or butadiene in the pathogenesis of leukemia.

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          Most cited references104

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          Benzene and leukemia. An epidemiologic risk assessment.

          To assess quantitatively the association between benzene exposure and leukemia, we examined the mortality rate of a cohort with occupational exposure to benzene. Cumulative exposure for each cohort member was estimated from historical air-sampling data and, when no sampling data existed, from interpolation on the basis of existing data. The overall standardized mortality ratio (a measure of relative risk multiplied by 100) for leukemia was 337 (95 percent confidence interval, 154 to 641), and that for multiple myeloma was 409 (95 percent confidence interval, 110 to 1047). With stratification according to levels of cumulative exposure, the standardized mortality ratios for leukemia increased from 109 to 322, 1186, and 6637 with increases in cumulative benzene exposure from less than 40 parts per million-years (ppm-years), to 40 to 199, 200 to 399, and 400 or more, respectively. A cumulative benzene exposure of 400 ppm-years is equivalent to a mean annual exposure of 10 ppm over a 40-year working lifetime; 10 ppm is the currently enforceable standard in the United States for occupational exposure to benzene. To examine the shape of the exposure-response relation, we performed a conditional logistic-regression analysis, in which 10 controls were matched to each cohort member with leukemia. From this model, it can be calculated that protection from benzene-induced leukemia would increase exponentially with any reduction in the permissible exposure limit.
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            Formaldehyde exposure and leukemia: a new meta-analysis and potential mechanisms.

            Formaldehyde is an economically important chemical, to which more than 2 million U.S. workers are occupationally exposed. Substantially more people are exposed to formaldehyde environmentally, as it is generated by automobile engines, is a component of tobacco smoke and is released from household products, including furniture, particleboard, plywood, and carpeting. The International Agency for Research on Cancer (IARC) recently classified formaldehyde as a human carcinogen that causes nasopharyngeal cancer and also concluded that there is "strong but not sufficient evidence for a causal association between leukemia and occupational exposure to formaldehyde". Here, we review the epidemiological studies published to date on formaldehyde-exposed workers and professionals in relation to lymphohematopoietic malignances. In a new meta-analysis of these studies, focusing on occupations known to have high formaldehyde exposure, we show that summary relative risks (RRs) were elevated in 15 studies of leukemia (RR=1.54; confidence interval (CI), 1.18-2.00) with the highest relative risks seen in the six studies of myeloid leukemia (RR=1.90; 95% CI, 1.31-2.76). The biological plausibility of this observed association is discussed and potential mechanisms proposed. We hypothesize that formaldehyde may act on bone marrow directly or, alternatively, may cause leukemia by damaging the hematopoietic stem or early progenitor cells that are located in the circulating blood or nasal passages, which then travel to the bone marrow and become leukemic stem cells. To test these hypotheses, we recommend that future studies apply biomarkers validated for other chemical leukemogens to the study of formaldehyde.
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              Cancer incidence in atomic bomb survivors. Part III. Leukemia, lymphoma and multiple myeloma, 1950-1987.

              This paper presents an analysis of data on the incidence of leukemia, lymphoma and myeloma in the Life Span Study cohort of atomic bomb survivors during the period from late 1950 through the end of 1987 (93,696 survivors accounting for 2,778,000 person-years). These analyses add 9 additional years of follow-up for leukemia and 12 for myeloma to that in the last comprehensive reports on these diseases. This is the first analysis of the lymphoma incidence data in the cohort. Using both the Leukemia Registry and the Hiroshima and Nagasaki tumor registries, a total of 290 leukemia, 229 lymphoma and 73 myeloma cases were identified. The primary analyses were restricted to first primary tumors diagnosed among residents of the cities or surrounding areas with Dosimetry System 1986 dose estimates between 0 and 4 Gy kerma (231 leukemias, 208 lymphomas and 62 myelomas). Analyses focused on time-dependent models for the excess absolute risk. Separate analyses were carried out for acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML), chronic myelocytic leukemia (CML) and adult T-cell leukemia (ATL). There were few cases of chronic lymphocytic leukemia in this population. There was strong evidence of radiation-induced risks for all subtypes except ATL, and there were significant subtype differences with respect to the effects of age at exposure and sex and in the temporal pattern of risk. The AML dose-response function was nonlinear, whereas there was no evidence against linearity for the other subtypes. When averaged over the follow-up period, the excess absolute risk (EAR) estimates (in cases per 10(4) PY Sv) for the leukemia subtypes were 0.6, 1.1 and 0.9 for ALL, AML and CML, respectively. The corresponding estimated average excess relative risks at 1 Sv are 9.1, 3.3 and 6.2 respectively. There was some evidence of an increased risk of lymphoma in males (EAR = 0.6 cases per 10(4) PY Sv) but no evidence of any excess in females. There was no evidence of an excess risk for multiple myeloma in our standard analyses.
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                Author and article information

                Contributors
                Journal
                J Occup Med Toxicol
                J Occup Med Toxicol
                Journal of Occupational Medicine and Toxicology (London, England)
                BioMed Central
                1745-6673
                2013
                22 May 2013
                : 8
                : 14
                Affiliations
                [1 ]Department of Hygiene, Epidemiology and Medical Statistics, University of Athens, Medical School, 75 Mikras Asias 115 27, Goudi, Athens, Greece
                [2 ]Occupational & Industrial Hygiene Department, National School of Public Health, 96 Alexandras Av. 11521, Athens, Greece
                Article
                1745-6673-8-14
                10.1186/1745-6673-8-14
                3668148
                23697536
                4c13a56e-732f-40fe-8567-5aef4974a252
                Copyright © 2013 Polychronakis et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 October 2012
                : 6 May 2013
                Categories
                Review

                Occupational & Environmental medicine
                leukemia,exposure,occupation,worker,work-related,hazard,risk-factor
                Occupational & Environmental medicine
                leukemia, exposure, occupation, worker, work-related, hazard, risk-factor

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