Lymphohematopoietic Cancers Research Articles

Health effects of occupational exposure to uranium: Do physicochemical properties matter?

Purpose: Physicochemical properties of uranium, including isotopic composition and solubility, are determinants of its toxicity. We reviewed epidemiological studies in civilian and military workers known to be exposed to uranium with different physicochemical properties to investigate its long-term effects, such as cancerous and circulatory diseases.Materials and methods: We systematically searched the Pubmed and the Scopus databases to identify studies of uranium- processing workers (published between 1980 and 2013) and veterans of the wars in the Persian Gulf and the Balkans (published between 1991 and 2013) in which defined outcomes, such as lung, lymphohematopoietic, kidney cancers, and circulatory diseases were examined. Results from these studies in terms of risk of each health outcome (mortality or incidence) and analyses of dose-response relationship were examined to present the impact of uranium physicochemical properties on the observed results.Results: Twenty-seven articles were reviewed. There is some evidence for increased lung cancer risk among uranium-processing workers. The evidence is less strong for lymphohematopoietic cancer. We found that most of the studies insufficiently assessed the physicochemical properties of uranium and some of them used proxies for the exposure assessment and risk estimation analyses. Studies of veterans of the wars in the Persian Gulf and the Balkans are uninformative in respect to internal uranium exposure.Conclusions: Existing epidemiological data on the physicochemical properties of uranium and associated health outcomes are inconclusive. Further studies among certain groups of uranium-processing workers (uranium-enrichment and fuel-fabrication workers) could contribute to our knowledge of the health effects of uranium with respect to its physicochemical properties.

0409 The North American Pooled Project (NAPP): Pooled analyses of case-control studies of pesticides and agricultural exposures, lymphohematopoietic cancers and sarcoma

ObjectivesPrevious studies have noted associations between specific pesticides and multiple cancer types. However, assessments for many pesticides have been limited by small numbers of exposed cases. To address this, we...

Lymphohematopoietic cancers induced by chemicals and other agents and their implications for risk evaluation: An overview.

Lymphohematopoietic neoplasia are one of the most common types of cancer induced by therapeutic and environmental agents. Of the more than 100 human carcinogens identified by the International Agency for Research on Cancer, approximately 25% induce leukemias or lymphomas. The objective of this review is to provide an introduction into the origins and mechanisms underlying lymphohematopoietic cancers induced by xenobiotics in humans with an emphasis on acute myeloid leukemia, and discuss the implications of this information for risk assessment. Among the agents causing lymphohematopoietic cancers, a number of patterns were observed. Most physical and chemical leukemia-inducing agents such as the therapeutic alkylating agents, topoisomerase II inhibitors, and ionizing radiation induce mainly acute myeloid leukemia through DNA-damaging mechanisms that result in either gene or chromosomal mutations. In contrast, biological agents and a few immunosuppressive chemicals induce primarily lymphoid neoplasms through mechanisms that involve alterations in immune response. Among the environmental agents examined, benzene was clearly associated with acute myeloid leukemia in humans, with increasing but still limited evidence for an association with lymphoid neoplasms. Ethylene oxide and 1,3-butadiene were linked primarily to lymphoid cancers. Although the association between formaldehyde and leukemia remains controversial, several recent evaluations have indicated a potential link between formaldehyde and acute myeloid leukemia. The four environmental agents examined in detail were all genotoxic, inducing gene mutations, chromosomal alterations, and/or micronuclei in vivo. Although it is clear that rapid progress has been made in recent years in our understanding of leukemogenesis, many questions remain for future research regarding chemically induced leukemias and lymphomas, including the mechanisms by which the environmental agents reviewed here induce these diseases and the risks associated with exposures to such agents.

Risk of myeloproliferative disease and chronic myeloid leukaemia following exposure to low-level benzene in a nested case–control study of petroleum workers

BackgroundBenzene exposure has been associated with increased risk of leukaemia and myelodysplastic syndrome. Existing studies are sparse for other lymphohaematopoietic cancer subtypes, such as myeloproliferative disease (MPD) and the related...

Compensation for occupational cancer.

The legal scope and criteria for occupational cancer in Korea was out of date. The aim of this study was to review the current criteria for occupational cancer and amend the existent criteria on the basis of recent scientific evidence. The scientific evidence and the legal list of occupational cancer were analyzed to identify the causes of occupational cancer on a global scale. The relationship between compensated occupational cancer cases and carcinogen exposure in Korea was examined. The factors associated with specific causes and target cancers were determined to produce additional criteria. Five-hundred and nineteen cases of 2,468 were awarded compensation for occupational cancer including lung, malignant mesothelioma, lymphohematopoietic, and liver cancers from January 2000 to October 2012. Between 1996 and 2005, benzene accounted for 84.4% of cases, and between 1999 and 2005, asbestos was associated with 62.3% of cases. Fourteen novel causative agents and 12 additional target cancers were identified and the final guidelines were amended to include 23 causative agents and 21 target cancers. This amendment of the criteria for occupational cancer represents the widest change in Korean history and is expected to improve the understanding of occupational cancer by providing an up-to-date and accurate reference guide.

Higher fetuin-A, lower adiponectin and free leptin levels mediate effects of excess body weight on insulin resistance and risk for myelodysplastic syndrome

ObjectiveExcess body weight has been implicated in the pathogenesis of myelodysplastic syndrome (MDS). We thus explored the role of serum fetuin-A reflecting ectopic hepatic fat deposition when storage capacity of adipocytes has been exceeded, free leptin reflecting overall fat mass and adiponectin reflecting visceral fat mass, all potential mediators of the effects of obesity on insulin resistance and, consequently, to MDS risk. Materials & MethodsIn a hospital-based case–control study, we studied 101 cases with incident, histologically confirmed primary MDS and 101 controls matched on gender, age and date of diagnosis, between 2004 and 2007. Serum fetuin-A, adiponectin, leptin, leptin receptor, free leptin and insulin were determined. ResultsHigher serum fetuin-A, lower adiponectin and lower free leptin were all individually and independently associated with higher risk of MDS before and after controlling for matching and risk factors, such as age, gender, date of diagnosis, body mass index (BMI), family history of lymphohematopoietic cancer, smoking history and serum insulin. Interestingly, we have shown that these associations were prominent among overweight/obese individuals and persisted after controlling for BMI and serum insulin indicating that their effects are above and beyond insulinemia only. ConclusionElevated serum fetuin-A but lower adiponectin and free leptin are associated with higher risk of MDS particularly among overweight/obese individuals. These findings suggest that the association between excessive weight gain and the risk of MDS could be mediated by fetuin-A, adiponectin and free leptin, which may have potential clinical and preventive implications.

Systematic review of the epidemiology literature on formaldehyde and lymphohematopoietic cancers

Background: EPA is currently drafting a Toxicological Review of formaldehyde. As part of the comprehensive evaluation of potential hazards associated with exposure to formaldehyde, the hazards for ...

Impact of chemical exposure on cancer mortality in a French cohort of uranium processing workers

Nuclear workers may be exposed to a variety of chemical hazards, in addition to radiation. We examined the effect of chemical exposures on cancer mortality among French uranium processing workers at the AREVA NC Pierrelatte facility. A cohort of 2,897 uranium processing workers employed for at least 6 months was followed from 1968 through 2006. Exposure to uranium and potentially carcinogenic chemicals was assessed with a plant-specific job-exposure matrix. Mortality hazard ratios (HRs) for cancers of the lung, lymphohematopoietic system, kidney and bladder, brain and central nervous system (BCNS), and prostate were estimated for each specific chemical exposure, with Cox regression models stratified for sex and calendar period and adjusted for socioeconomic status. Additional adjustments enabled us to examine the effect of co-exposure to uranium and other chemicals. Exposure to aromatic solvents was associated with increased risk of BCNS malignancies after adjustment for other chemicals (HR=6.53, 95% CI=1.14-37.41; n=6) and for other chemicals and uranium (HR=7.26, 95% CI=0.90-58.19) in the annual exposure status model. Selected groups of lymphohematopoietic cancers were found associated with solvent exposure. Inconclusive results were found regarding chromium (VI) exposure, since only 2 workers died from lung cancer among 109 exposed. Based on our pilot study, it seemed important to take into account chemical exposures in the analyses of cancer mortality among French uranium processing workers.

Cancer Mortality of Workers Exposed to Styrene in the U.S. Reinforced Plastics and Composite Industry

Epidemiologic studies have reported increased risk of lymphohematopoietic cancers, lung cancer, and pancreatic cancer after exposure to styrene, although findings across studies are not consistent. We update a large study of reinforced plastic industry workers with relatively high exposures to styrene, examining cancer risks associated with exposure levels. The study includes 15,826 workers who were exposed between 1948 and 1977 with vital-status follow-up from 1948 to 2008. We examine mortality rates associated with cumulative exposure, duration of exposure, peak exposures, average exposure, and time since first exposure to styrene. Exposure estimates were truncated starting in 1977, the period with the lowest exposures, leaving 27% of the study group with incomplete work histories. The standardized mortality ratios were 0.84 (95% confidence interval = 0.69-1.02) for all lymphatic and hematopoietic cancers combined, 0.72 (0.50-1.00) for non-Hodgkin lymphoma, and 0.84 (0.60-1.14) for leukemia. There was no trend with either cumulative exposure to styrene or number of peaks. Pancreatic cancer deaths were at expected levels (0.96 [0.73-1.22]). There were more lung cancer deaths than expected (1.34 [1.23-1.46]), although with a marked inverse trend with cumulative exposure. We found no coherent evidence that styrene exposure increases risk from cancers of the lymphatic and hematopoietic tissue, pancreas, or lung.

A Systematic Review of Carcinogenic Outcomes and Potential Mechanisms from Exposure to 2,4-D and MCPA in the Environment.

Chlorophenoxy compounds, particularly 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxy)acetic acid (MCPA), are amongst the most widely used herbicides in the United States for both agricultural and residential applications. Epidemiologic studies suggest that exposure to 2,4-D and MCPA may be associated with increased risk non-Hodgkins lymphoma (NHL), Hodgkin's disease (HD), leukemia, and soft-tissue sarcoma (STS). Toxicological studies in rodents show no evidence of carcinogenicity, and regulatory agencies worldwide consider chlorophenoxies as not likely to be carcinogenic or unclassifiable as to carcinogenicity. This systematic review assembles the available data to evaluate epidemiologic, toxicological, pharmacokinetic, exposure, and biomonitoring studies with respect to key cellular events noted in disease etiology and how those relate to hypothesized modes of action for these constituents to determine the plausibility of an association between exposure to environmentally relevant concentrations of 2,4-D and MCPA and lymphohematopoietic cancers. The combined evidence does not support a genotoxic mode of action. Although plausible hypotheses for other carcinogenic modes of action exist, a comparison of biomonitoring data to oral equivalent doses calculated from bioassay data shows that environmental exposures are not sufficient to support a causal relationship. Genetic polymorphisms exist that are known to increase the risk of developing NHL. The potential interaction between these polymorphisms and exposures to chlorophenoxy compounds, particularly in occupational settings, is largely unknown.

Myelodysplastic Syndrome and Benzene Exposure Among Petroleum Workers: An International Pooled Analysis

BackgroundBenzene at high concentrations is known to cause acute myeloid leukemia (AML), but its relationship with other lymphohematopoietic (LH) cancers remains uncertain, particularly at low concentrations. In this pooled analysis, we examined the risk of five LH cancers relative to lower levels of benzene exposure in petroleum workers.MethodsWe updated three nested case–control studies from Australia, Canada, and the United Kingdom with new incident LH cancers among petroleum distribution workers through December 31, 2006, and pooled 370 potential case subjects and 1587 matched LH cancer-free control subjects. Quantitative benzene exposure in parts per million (ppm) was blindly reconstructed using historical monitoring data, and exposure certainty was scored as high, medium, or low. Two hematopathologists assigned diagnoses and scored the certainty of diagnosis as high, medium, or low. Dose–response relationships were examined for five LH cancers, including the three most common leukemia cell-types (AML, chronic myeloid leukemia [CML], and chronic lymphoid leukemia [CLL]) and two myeloid tumors (myelodysplastic syndrome [MDS] and myeloproliferative disease [MPD]). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression, controlling for age, sex, and time period.ResultsCumulative benzene exposure showed a monotonic dose–response relationship with MDS (highest vs lowest tertile, >2.93 vs ≤0.348 ppm-years, OR = 4.33, 95% CI = 1.31 to 14.3). For peak benezene exposures (>3 ppm), the risk of MDS was increased in high and medium certainty diagnoses (peak exposure vs no peak exposure, OR = 6.32, 95% CI = 1.32 to 30.2) and in workers having the highest exposure certainty (peak exposure vs no peak exposure, OR = 5.74, 95% CI = 1.05 to 31.2). There was little evidence of dose–response relationships for AML, CLL, CML, or MPD.ConclusionsRelatively low-level exposure to benzene experienced by petroleum distribution workers was associated with an increased risk of MDS, but not AML, suggesting that MDS may be the more relevant health risk for lower exposures.

Relationship between the paraoxonase 1 (PON1) M55L and Q192R polymorphisms and lymphohaematopoietic cancers in a Greek agricultural population

The aim of this study was to investigate the association between Paraoxonase 1 (PON1) gene polymorphisms (M55L and Q192R) and lymphohaematopoietic cancers (LHC) in an agricultural region of Greece. A hospital-based case–control study was conducted. A structured questionnaire including information on demographics, residence, occupation, agricultural practices, pesticide exposure, family history, smoking, alcohol consumption and medical history, was used. Genotyping of 316 cases of LHC and 351 healthy controls by using standard laboratory methods was performed. To control for confounders, Binary and Multinomial Logistic Regression analyses were used.Possession of QQ genotype or presence of the Q allele were associated with increased risk of developing LHC (OR 1.94, 95% CI 1.42–2.66 and OR 1.72, 95% CI 1.33–2.23 respectively). The QQ genotype in the recessive model was independently associated with LHC (OR 1.92, 95% CI 1.40–2.65), leukaemia (OR 1.99, 95% CI 1.13–3.49), lymphoma (OR 2.17, 95% CI 1.21–3.90) and plasmacell disease (OR 1.92, 95% CI 1.40–2.65) even after controlling for age, sex, pesticide exposure, smoking and family history (cancers, LHC and immunological disorders) as confounders. Possession of QQ genotype was found to have a stronger association with LHC in the high and medium pesticide exposed groups(OR 2.15, 95% CI 1.35–3.40, P-value 0.001 and OR 2.25, 95% CI 1.21–4.19, P-value 0.010 respectively), compared with the Low/No exposed group where the association was not statistically significant (OR 1.51, 95% CI 0.76–3.00, P-value 0.224). We found no association between M55L polymorphism and LHC. PON1 polymorphisms may influence the risk for LHC in our agricultural area. The results encourage further investigation on the PON1 polymorphisms and their importance on the individual's susceptibility especially when exposure to pesticides occurs.

Genotoxicity of styrene-7,8-oxide and styrene in Fisher 344 rats: A 4-week inhalation study

The cytogenetic alterations in leukocytes and the increased risk for leukemia, lymphoma, or all lymphohematopoietic cancer observed in workers occupationally exposed to styrene have been associated with its hepatic metabolisation into styrene-7,8-oxide, an epoxide which can induce DNA damages. However, it has been observed that styrene-7,8-oxide was also found in the atmosphere of reinforced plastic industries where large amounts of styrene are used. Since the main route of exposure to these compounds is inhalation, in order to gain new insights regarding their systemic genotoxicity, Fisher 344 male rats were exposed in full-body inhalation chambers, 6h/day, 5 days/week for 4 weeks to styrene-7,8-oxide (25, 50, and 75ppm) or styrene (75, 300, and 1000ppm). Then, the induction of micronuclei in circulating reticulocytes and DNA strand breaks in leukocytes using the comet assay was studied at the end of the 3rd and 20th days of exposure. Our results showed that neither styrene nor styrene-7,8-oxide induced a significant increase of the micronucleus frequency in reticulocytes or DNA strand breaks in white blood cells. However, in the presence of the formamidopyridine DNA glycosylase, an enzyme able to recognize and excise DNA at the level of some oxidized DNA bases, a significant increase of DNA damages was observed at the end of the 3rd day of treatment in leukocytes from rats exposed to styrene but not to styrene-7,8-oxide. This experimental design helped to gather new information regarding the systemic genotoxicity of these two chemicals and may be valuable for the risk assessment associated with an occupational exposure to these molecules.

Patterns of Mortality among Wisconsin Uniroyal Tire Manufacturing Workers

The goal of this analysis was to determine the patterns of mortality among deceased workers of the former Uniroyal, Inc. Plant in Eau Claire, Wisconsin, who were exposed to solvents. After collecting information on cause of death, we conducted a standardized proportional mortality ratio (PMR) and proportional cancer mortality ratio (PCMR) analysis. The results of the PCMR analysis indicate that former Uniroyal workers experienced elevated mortality due to cancers, especially lymphohematopoietic cancers, compared to other Wisconsin decedents. The former workers and family members were pursuing litigation at the time of publication. We received the list of deceased workers from plaintiffs' attorney and were compensated for conducting the analysis; the funder did not directly participate in any part of the study or influence the results. We conclude there is evidence of excess lymphohematopoietic cancer in this worker cohort.

Cancer morbidity of professional emergency responders in Korea

ObjectivesMany professional emergency responders in Korea have cross-trained and served in multiple roles depending upon the nature of the emergency incident. Therefore firefighters and other emergency responders in Korea have...

Lymphohaematopoietic cancers and benzene: a pooled analysis of petroleum workers

ObjectivesThere are few quantitative studies on the effect of relatively low benzene concentrations on risks of specific lymphohaematopoietic cancer subtypes. Three nested case-control studies among petroleum workers in Australia, Canada...

P1-311 Lymphohematopoietic cancers and benzene: a pooled analysis of petroleum workers

IntroductionThere are few quantitative studies on the effect of relatively low benzene concentrations on risks of specific lymphohematopoietic cancer subtypes. Three nested case-control studies among petroleum workers in Australia, Canada...

Mortality patterns of Australian male farmers and farm managers

To compare the all-cause and specific-cause death rates of Australian male farmers and farm managers aged 25-74 years, with other Australian men. Data were extracted from the Australian Bureau of Statistics Death Registration Collection covering the calendar years of 1999-2002. Denominator data for male farmers and farm managers were drawn from the 2001 Australian Population Census. Direct age-standardized death rates were calculated and compared with the general Australian male population. The 4025 male farmers or farm managers who died in this period represented 3.35% of all male deaths in the 25-74 year age range. The all-cause death rate for farmers and farm managers (730/100,000) was 33% higher than that of the Australian male population of the same age (549/100,000) (standardized mortality ratio (SMR)=1.33). Causes of death related to neoplasms (SMR=1.37), circulatory disease (SMR=1.40) and all external causes (SMR=1.37), were all statistically higher than the comparison population. Within these groupings, ischaemic heart disease (SMR=1.39), other circulatory disease (SMR=1.42), prostate cancer (SMR=2.40), lymphohaematopoietic cancer (SMR=1.80) and transport injuries (SMR=2.06), were all significantly higher. These data indicate that Australian male farmers and farm managers are a disadvantaged group in terms of health status. The elevated rates of all-cause and specific-cause mortality compared with the Australian comparison population, illustrate both the need and scope for further investigation of these issues.

Styrene exposure and risk of cancer

Styrene is widely used in the manufacture of synthetic rubber, resins, polyesters and plastics. Styrene and the primary metabolite styrene-7,8-oxide are genotoxic and carcinogenic. Long-term chemical carcinogenesis bioassays showed that styrene caused lung cancers in several strains of mice and mammary cancers in rats and styrene-7,8-oxide caused tumours of the forestomach in rats and mice and of the liver in mice. Subsequent epidemiologic studies found styrene workers had increased mortality or incidences of lymphohematopoietic cancers (leukaemia or lymphoma or all), with suggestive evidence for pancreatic and esophageal tumours. No adequate human studies are available for styrene-7,8-oxide although this is the primary and active epoxide metabolite of styrene. Both are genotoxic and form DNA adducts in humans.

Cancer Incidence and Mortality in Swedish Sterilant Workers Exposed to Ethylene Oxide: Updated Cohort Study Findings 1972–2006

Objectives:To assess whether cancer incidence, mainly from lymphohaematopoietic tumours and breast cancer, and mortality were increased in a cohort of Swedish sterilant workers exposed to low levels of ethylene oxide (EtO), updated with 16 more years of follow up.Methods:The mortality and cancer incidence 1972–2006 experienced by a cohort of 2,171 male and female workers employed for at least one year in two plants producing medical equipment sterilised with EtO were investigated. Individual cumulative exposure to EtO was assessed by occupational hygienists. Cause-specific standardized rate ratios were calculated using the regional general population as a comparison for mortality (SMR) and cancer incidence (SIR). Internal Poisson-regression analyses were performed for selected causes.Results:The median cumulative exposure to EtO was 0.13 ppm-years. The overall cancer incidence was close to unity (SIR 0.94, 95% CI 0.82–1.08). Eighteen cases of lymphohaematopoietic cancer were observed (SIR 1.25, 95% CI 0.74–1.98). A healthy worker effect was indicated from a significantly decreased overall mortality and mortality from cardiovascular diseases. Internal analyses found significantly increased rate ratios for breast cancer for the two upper quartiles of cumulative exposure as compared to the lowest 50% of the cohort (IRR 2.76, 95% CI 1.20–6.33 and IRR 3.55, 95% CI 1.58–7.93).Conclusions:The findings from this updated study indicate limited or low risks for human cancer due to occupational exposure from ethylene oxide at the low cumulative exposure levels in this cohort. However a positive exposure-response relation with breast cancer was observed though.