Mortality and cancer incidence in a population exposed to TCDD after the Seveso, Italy, accident (1976-2013).

OBJECTIVES: The Seveso accident (1976) caused the contamination with 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) in an area north of Milan, Italy. We report the results of the update of mortality and cancer incidence in the exposed population through 2013. METHODS: The study cohort includes subjects living in three contaminated zones with decreasing TCDD soil concentrations (zone A, B and R) and in a surrounding uncontaminated territory (reference). Poisson models stratified/adjusted for gender, age and period were fitted to calculate rate ratios (RRs) and 95% CIs. RESULTS: In zone A in males, we found elevated mortality from circulatory diseases in the first decade after the accident (17 deaths, RR 2.00, 95% CI 1.24 to 3.23). In females, mortality from diabetes mellitus was increased, with a positive trend across zones. Incidence of soft tissue sarcoma was increased in males in zone R in the first decade (6 cases, RR 2.62, 95% CI 1.01 to 6.83). In females in zone B, there was an excess of non-Hodgkin's lymphoma after 30 years (6 cases, RR 2.87, 95% CI 1.14 to 7.23). Multiple myeloma was increased in the second decade in females in zone B (4 cases, RR 5.09, 95% CI 1.82 to 14.2) and in males in zone R (11 cases, RR 2.15, 95% CI 1.08 to 4.26). In males in zone R, there was a leukaemia excess after 30 years (23 cases, RR 2.02, 95% CI 1.04 to 3.93). CONCLUSIONS: Although with different patterns across gender, zone and time, we confirmed previous results of increased cardiovascular diseases, diabetes, soft tissue sarcoma, and lymphatic and haematopoietic cancers.

Myocardial work-A new tool for early detection of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone chemotherapy induced-cardiotoxicity in hematological patients.

BACKGROUND: Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (RCHOP) chemotherapy in non-Hodgkin's lymphoma (NHL) has risk of cardiotoxicity. PURPOSE: To determine the role of myocardial work and biomarkers in subclinical diagnosis and prediction of cardiotoxicity. METHODS: The 130 NHL patients (52 ± 9 years, 62% men) scheduled for RCHOP, with LVEF>50%, were evaluated at baseline, after third cycle and chemotherapy completion for 3D LVEF, 2D myocardial deformation (longitudinal, radial, circumferential strain - LS, RS, CS) and myocardial work (global constructive work, waste work, work index and work efficiency - GCW, GWW, GWI, GWE). NT-pro-BNP and troponin I were determined. RESULTS: After chemotherapy ended, 37 patients (28%) (group I) developed asymptomatic cardiotoxicity (8 mild form, 25 moderate form, 4 severe form); 93 patients (group II) did not. After third cycle, all patients had decreased LS, CS, RS, GCW, GWI, GWE and increased GWW, persistent after chemotherapy completion, with significant changes in group I. After third cycle, GWE and GCW were the best independent predictors for LVEF reduction; GWE decrease with>5% after third cycle predicted cardiotoxicity after chemotherapy completed (91% sensitivity, 94% specificity). CONCLUSIONS: In NHL, myocardial work can diagnose subclinical cardiotoxicity and predict LVEF decline. These parameters should be used for sensitive evaluation of myocardial function during chemotherapy.

Environmental pesticide exposure and non-Hodgkin lymphoma survival: a population-based study.

BACKGROUND: There is evidence indicating that pesticide exposure is a risk factor for non-Hodgkin lymphoma (NHL) development. However, the association between pesticide exposure and NHL survival is not well-established. METHODS: Using the California Cancer Registry, we identified patients with a first primary diagnosis of NHL from 2010 to 2016 and linked these patients with CalEnviroScreen 3.0 to obtain production agriculture pesticide exposure to 70 chemicals from the state-mandated Pesticide Use Reporting (PUR) by census tract from 2012 to 2014. In addition, data from PUR was integrated into a geographic information system that employs land-use data to estimate cumulative exposure to specific pesticides previously associated with NHL (glyphosate, organophosphorus, carbamate, phenoxyherbicide, and 2,4-dimethylamine salt) between 10 years prior up to 1 year after NHL diagnosis. Multivariable Cox proportional hazards regression models were used to evaluate the association between total pesticide exposure from CalEnviroScreen 3.0 and individual pesticide exposure from geographic land use data and lymphoma-specific and overall survival. RESULTS: Among 35,808 NHL patients identified, 44.2% were exposed to pesticide in their census tract of residence. Glyphosate, organophosphorus, carbamate, phenoxyherbicide, and 2,4-dimethylamine salt exposure was observed in 34.1%, 26.0%, 10.6%, 14.0%, and 12.8% of NHL patients, respectively. Total pesticide exposure at the time of diagnosis was not associated with lymphoma-specific or overall survival. In addition, no association was consistently found between glyphosate, organophosphorus, carbamate, phenoxyherbicide, and 2,4 dimethylamine salt exposure and lymphoma-specific or overall survival. CONCLUSIONS: Although we found no consistent associations between agricultural pesticide exposure at the neighborhood level and worse survival, these results provide a platform for designing future studies to determine the association between pesticide and NHL.

Herbicide use in farming and other jobs in relation to non-Hodgkin's lymphoma (NHL) risk.

OBJECTIVES: Given mixed evidence for carcinogenicity of current-use herbicides, we studied the relationship between occupational herbicide use and risk of non-Hodgkin's lymphoma (NHL) in a large, pooled study. METHODS: We pooled data from 10 case-control studies participating in the International Lymphoma Epidemiology Consortium, including 9229 cases and 9626 controls from North America, the European Union and Australia. Herbicide use was coded from self-report or by expert assessment in the individual studies, for herbicide groups (eg, phenoxy herbicides) and active ingredients (eg, 2,4-dichlorophenoxyacetic acid (2,4-D), glyphosate). The association between each herbicide and NHL risk was estimated using logistic regression to produce ORs and 95% CIs, with adjustment for sociodemographic factors, farming and other pesticides. RESULTS: We found no substantial association of all NHL risk with ever-use of any herbicide (OR=1.10, 95% CI: 0.94 to 1.29), nor with herbicide groups or active ingredients. Elevations in risk were observed for NHL subtypes with longer duration of phenoxy herbicide use, such as for any phenoxy herbicide with multiple myeloma (>25.5 years, OR=1.78, 95% CI: 0.74 to 4.27), 2,4-D with diffuse large B-cell lymphoma (>25.5 years, OR=1.47, 95% CI: 0.67 to 3.21) and other (non-2,4-D) phenoxy herbicides with T-cell lymphoma (>6 years, lagged 10 years, OR=3.24, 95% CI: 1.03 to 10.2). An association between glyphosate and follicular lymphoma (lagged 10 years: OR=1.48, 95% CI: 0.98 to 2.25) was fairly consistent across analyses. CONCLUSIONS: Most of the herbicides examined were not associated with NHL risk. However, associations of phenoxy herbicides and glyphosate with particular NHL subtypes underscore the importance of estimating subtype-specific risks.

Impact of occupational pesticide exposure assessment method on risk estimates for prostate cancer, non-Hodgkin's lymphoma and Parkinson's disease: results of three meta-analyses.

Assessment of occupational pesticide exposure in epidemiological studies of chronic diseases is challenging. Biomonitoring of current pesticide levels might not correlate with past exposure relevant to disease aetiology, and indirect methods often rely on workers' imperfect recall of exposures, or job titles. We investigated how the applied exposure assessment method influenced risk estimates for some chronic diseases. In three meta-analyses the influence of exposure assessment method type on the summary risk ratio (sRR) of prostate cancer (PC) (25 articles), non-Hodgkin's lymphoma (NHL) (29 articles) and Parkinson's disease (PD) (32 articles) was investigated. Exposure assessment method types analysed were: group-level assessments (eg, job titles), self-reported exposures, expert-level assessments (eg, job-exposure matrices) and biomonitoring (eg, blood, urine). Additionally, sRRs were estimated by study design, publication year period and geographic location where the study was conducted. Exposure assessment method types were not associated with statistically significant different sRRs across any of the health outcomes. Heterogeneity in results varied from high in cancer studies to moderate and low in PD studies. Overall, case-control designs showed significantly higher sRR estimates than prospective cohort designs. Later NHL publications showed significantly higher sRR estimates than earlier. For PC, studies from North America showed significantly higher sRR estimates than studies from Europe. We conclude that exposure assessment method applied in studies of occupational exposure to pesticides appears not to have a significant effect on risk estimates for PC, NHL and PD. In systematic reviews of chronic health effects of occupational exposure to pesticides, epidemiological study design, publication year and geographic location, should primarily be considered.

Dietary exposure to polychlorinated biphenyls (PCB) and risk of Non-Hodgkin's lymphoma: Evidence from the French E3N prospective cohort.

INTRODUCTION: Polychlorinated biphenyls (PCB) are persistent and bioaccumulative lipophilic substances, mostly used in the past by industry. Known to be cancerogenic, PCB are suspected to increase Non-Hodgkin's Lymphoma (NHL) risk in the general population mainly due to evidence from cases-controls studies. Since their interdiction in 1987, diet represents the main route of exposure for the general population, nevertheless no study has assessed the relationship between PCB dietary exposure and NHL risk. The aim of this study was to analyze the association between dietary exposures to dioxin like PCB (DL PCB) and non-dioxin like PCB (NDL PCB) and NHL risk in the E3N prospective cohort of French women. MATERIALS AND METHODS: Among 67,879 women included in this study, 457 cases of NHL were confirmed during 21 years of follow-up. Dietary exposure to PCB was estimated combining food consumption data collected in E3N and food contamination data provided by French Agency for Food, Environmental and Occupational Health & Safety (ANSES) in the second French total diet study. Cox regression models, adjusted for potential confounders, were used to estimate hazard ratio (HR) and 95% confidence intervals (CI). RESULTS: Average age at diagnosis was 67 years. The median dietary exposure to DL PCB and NDL PCB was, 18.5 pg TEQ/d and 138,843.2 pg/d, respectively. While no association was found between dietary exposure to DL PCB or NDL PCB and overall NHL risk, analyses by NHL histological subgroups showed a positive association between dietary exposures to DL PCB and Diffuse Large B Cell Lymphoma (OR3vs1 1.90, 95%CI [1.03-3.51], ptrend 0.02). Nevertheless these findings were no longer statistically significant when the models were adjusted for fish and dairy products consumption. In addition, an inverse association was found between dietary exposure to NDL PCB and the risk of follicular lymphoma (OR3vs1 0.46, 95%CI [0.24-0.87], ptrend 0.01). CONCLUSION: This is the first study to evaluate the association between dietary exposure to DL and NDL PCB and the risk of NHL in a prospective cohort study. Overall, the findings suggest a lack of association between dietary exposure to DL or NDL PCB and NHL risk. Additional studies are needed to reproduce these findings.

A systematic review and meta-analysis of occupational exposures and risk of follicular lymphoma.

BACKGROUND: The etiology of follicular lymphoma (FL), a common non-Hodgkin lymphoma subtype, is largely unknown. OBJECTIVE: We performed a systematic review and meta-analysis of observational studies examining the relationship between occupational exposures and FL risk. METHODS: We searched Ovid MEDLINE, Ovid EMBASE, and Web of Science for eligible observational studies examining job titles or occupational exposures prior to January 1, 2020. We performed a narrative synthesis and used random-effects models to generate meta-estimates of relative risk (RR) with 95% confidence intervals (95%CI) for exposures reported by three or more studies. RESULTS: Fifty-eight studies were eligible. Ten cohort and 37 case-control studies quantified FL risk in relation to any exposure to one or more occupational groups or agents. Eight cohort and 19 case-control studies examined dose-response relationships. We found evidence of a positive association with increasing plasma concentration of dichlorodiphenyldichloroethylene (DDE; meta-RR = 1.51, 95%CI = 0.99, 2.31; I2 = 0.0%) and polychlorinated biphenyls (PCBs; meta-RR = 1.47, 95%CI = 0.97, 2.24; I2 = 8.6%). We observed a positive association with exposure to any solvent (meta-RR = 1.16, 95%CI = 1.00, 1.34; I2 = 0.0%) and chlorinated solvents (meta-RR = 1.35, 95%CI = 1.09, 1.68; I2 = 0.0%). Single studies reported a significant positive dose-response association for exposure to any pesticide, hexachlorobenzene, any organophosphate, diazinon, metolachlor, carbaryl, lindane, trichloroethylene, oils/greases, and extremely low-frequency magnetic fields. Job title-only analyses suggested increased risk for medical doctors and spray painters, and decreased risk for bakers and teachers. Overall, studies demonstrated low risk of bias, but most studies examined small numbers of exposed cases. CONCLUSIONS: Current evidence indicates a positive association between FL and occupational exposure to DDE, PCBs, any solvent and chlorinated solvents. Our findings may help guide policies and practices on the safe use of solvents and inform models of lymphomagenesis. Future studies with larger sample sizes and comprehensive quantitative exposure measures may elucidate other avoidable carcinogenic exposures.

Exposure to glyphosate and risk of non-Hodgkin lymphoma: an updated meta-analysis.

OBJECTIVE: We updated a recent systematic review and meta-analysis of epidemiologic studies to help clarifying the association between exposure to glyphosate and risk of non-Hodgkin lymphoma (NHL). METHODS: We conducted an updated search of the literature, and identified a total of 15 relevant publications, from which we extracted results from six non-overlapping studies. We performed random-effects meta-analyses for ever-exposure to glyphosate, dose-response, and risk of specific NHL subtypes Results: The meta-RR for ever-exposure to glyphosate was 1.05 (95% confidence interval [CI] 0.90-1.24; I2 = 0%). The meta-RR for the highest category of exposure was 1.15 (95% CI 0.72-1.83; 3 studies). The meta-RR for diffuse large B-cell lymphoma (DLBCL) was 1.29 (95% CI 1.02-1.63; 4 studies), that for follicular lymphoma was 0.84 (95% CI 0.61-1.17), and that for chronic lymphocytic leukemia/small lymphocytic lymphoma was 1.33 (95% CI 0.65-2.70). There was indication of publication bias. CONCLUSIONS: This updated meta-analysis reinforces our previous conclusion of a lack of an association between exposure to glyphosate and risk of NHL overall, although an association with DLBCL cannot be ruled out.

Prediagnostic serum concentrations of organochlorine pesticides and non-Hodgkin lymphoma: A nested case-control study in the Norwegian Janus Serum Bank Cohort.

BACKGROUND: Much of the marked increase in incidence of non-Hodgkin lymphoma (NHL) over the past few decades remains unexplained. Organochlorines, including organochlorine pesticides (OCPs), have been implicated as possible contributors to the increase, but the evidence is inconsistent. OBJECTIVES: To investigate the relation between pre-diagnostic levels of OCPs and risk of NHL in a case-control study nested within the population-based Janus Serum Bank Cohort in Norway. METHODS: Prediagnostic concentrations of 11 OCPs or OCP metabolites were measured in baseline blood samples collected between 1972 and 1978 from 190 cases and 190 controls matched on sex, county, age at blood draw, and date of blood draw. We conducted conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for each quartile of lipid-corrected OCP/metabolite relative to the lowest quartile. RESULTS: We observed non-significantly elevated ORs across quartiles of ß-hexachlorocyclohexane compared to the lowest quartile (OR range: 1.40-1.82) although with no apparent monotonic exposure-response relationship. We also found an inverse association between risk of NHL and o,p'-DDT (OR for Q4 vs. Q1 = 0.44, 95% CI: 0.19, 1.01; p-trend = 0.05). In analyses stratified by age at blood collection and duration of follow-up, several other analytes, primarily chlordane-related compounds, showed inverse associations among younger participants or those with longer follow-up time between blood draw and NHL diagnosis. CONCLUSIONS: We found only limited evidence of positive association between selected OCPs and development of NHL.

Long-term exposure to PM2.5 and its constituents and risk of Non-Hodgkin lymphoma in Denmark: A population-based case-control study.

BACKGROUND: Particulate matter (PM) air pollution is a complex mixture and the various PM constituents likely affect health differently. The literature on the relationships among specific PM constituents and the risk of cancer is sparse. In this study, we aimed to evaluate the association of PM2.5 and its constituents with the incidence of non-Hodgkin lymphoma (NHL) and the two main NHL subtypes. METHODS: We undertook a nationwide register-based case-control study including 20,847 cases registered in the Danish Cancer Registry with NHL between 1989 and 2014. Among the entire Danish population, we selected 41,749 age and sex-matched controls randomly from the Civil Registration System. We assessed modelled outdoor PM concentrations at addresses of cases and controls with a state-of-the-art multi scale air pollution modelling system and used conditional logistic regression to estimate odds ratios (ORs) adjusted for individual and neighborhood level socio-demographic variables. RESULTS: The 10-year time-weighted average concentrations of PM2.5, primary carbonaceous particles (BC/OC), secondary inorganic aerosols (SIA), secondary organic aerosols (SOA) and sea salt were 17.4, 2.3, 7.8, 0.3, and 4.1 µg/m3, respectively among controls. The results showed higher risk for NHL in association with exposure to BC/OC (OR = 1.03; 95% CI: 1.00, 1.07, per interquartile range (IQR)) and SOA (OR = 1.54; 95% CI: 1.13, 2.09, per IQR). The results indicated a higher risk for follicular lymphoma in association with several PM components. Including PM2.5 (OR = 1.16; 95% CI: 0.98-1.38), BC/OC (OR = 1.05; 95% CI: 0.97-1.14), SIA (OR = 1.44; 95% CI: 0.80-1.08), SOA (OR = 4.52; 95% CI: 0.86-23.83) per IQR. CONCLUSION: This is the first study on PM constituents and the risk of NHL. The results indicated an association with primary carbonaceous and secondary organic PM. The results need replication in other settings before any firm conclusion can be reached.

Benzene exposure-response and risk of lymphoid neoplasms in Chinese workers: A multicenter case-cohort study.

BACKGROUND: While international agreement supports a causal relationship of benzene exposure with acute myeloid leukemia, there is debate about benzene and lymphoid neoplasm risks. METHODS: In a case-cohort study with follow-up of 110 631 Chinese workers during 1972-1999, we evaluated benzene exposure-response for non-Hodgkin lymphoma (NHL), lymphoid leukemias (LL), acute lymphocytic leukemia (ALL), and total lymphoid neoplasms (LN). We estimated benzene exposures using state-of-the-art hierarchical modeling of occupational factors calibrated with historical routine measurements and evaluated cumulative exposure-response using Cox regression. RESULTS: NHL and other specified LN were increased in exposed vs unexposed workers. However, there was no evidence of exposure-response for NHL or other specified LN. Based on a linear exposure-response, relative risks at 100 parts per million-years (RR at 100 ppm-years) for cumulative benzene exposure using a 2-year lag (exposure at least 2 years before the time at risk) were 1.05 for NHL (95 percent confidence interval (CI) = 0.97, 1.27; 32 cases), 1.11 for LL (95% CI < 0, 1.66; 12 cases), 1.21 for ALL (95% CI < 0, 3.53; 10 cases), and 1.02 for total LN (95% CI < 0, 1.16; 49 cases). No statistically significant exposure-response trends were apparent for these LN for 2 to <10-year or ≥10-year lags. NHL risks were not significantly modified by sex, age, or year at first exposure, attained age, or time since exposure. CONCLUSION: Given the study strengths and limitations, we found little evidence of exposure-response for benzene and NHL, LL, ALL, or total LN, although NHL and other specified LN were increased in exposed vs unexposed individuals.

The Potential Effects of Recall Bias and Selection Bias on the Epidemiological Evidence for the Carcinogenicity of Glyphosate.

Glyphosate is a widely used herbicide worldwide. The International Agency for Research on Cancer in 2015 declared that glyphosate is probably carcinogenic to humans, noting a positive association for non-Hodgkin lymphoma (NHL). The principal human data on glyphosate and NHL come from five case-control studies and two cohort studies. The case-control studies are at risk of recall bias resulting from information on exposure to pesticides being collected from cases and controls based on their memories. In addition, two of the case-control studies are additionally at risk of a form of selection bias that can exacerbate the effect of recall bias. Both biases are in the direction of making glyphosate appear carcinogenic. If odds ratios (ORs) are not biased and a pesticide plays no role in causing NHL, the probability that an OR for that pesticide is greater than 1.0 is approximately 0.5. The fractions of ORs for pesticides other than glyphosate that are greater than 1.0 in the case-control studies are 0.90 (n = 92), 0.90 (n = 152), 0.93 (n = 59), 0.76 (n = 140), and 0.53 (n = 54), the first two from studies that are at risk for both types of bias. In the two cohort studies, which are not subject to these biases, the comparable fractions for relative risks for all cancers are 0.51 (n = 70) and 0.48 (n = 158). These results comply closely with what would be expected if evidence for carcinogenicity of glyphosate in these studies results from statistical bias in the case-control studies.

Occupational exposure to formaldehyde and risk of non hodgkin lymphoma: a meta-analysis.

BACKGROUND: Formaldehyde, a widely used chemical, is considered a human carcinogen. We report the results of a meta-analyses of studies on the relationship between occupational exposure to formaldehyde and risk of non-Hodgkin lymphoma (NHL). METHODS: We performed a systematic review and meta-analysis according to international guidelines and we identified 12 reports of occupational populations exposed to formaldehyde. We evaluated inter-study heterogeneity and we applied a random effects model. We conducted a cumulative meta-analysis and a meta-analysis according to estimated average exposure of each study population. RESULTS: The meta-analysis resulted in a summary relative risk (RR) for NHL of 0.93 (95% confidence interval 0.83-1.04). The cumulative meta-analysis suggests that higher RRs were detected in studies published before 1986, while studies available after 1986 did not show an association. No differences were found between different levels of occupational exposure. Conclusions Notwithstanding some limitations, the results of this meta-analysis do not support the hypothesis of an association between occupational exposure to formaldehyde and risk of NHL.

Tumor necrosis factor-alpha inhibitors and risk of non-Hodgkin lymphoma in a cohort of adults with rheumatologic conditions.

Based on limited evidence, the U.S. Food and Drug Administration (FDA) issued a black box warning for the use of tumor necrosis factor-alpha inhibitors (TNFIs) and risk of non-Hodgkin lymphoma (NHL). Our objective was to determine the risk of NHL associated with TNFI use by duration and type of anti-TNF agent. We performed a nested case-control study within a retrospective cohort of adults with rheumatologic conditions from a U.S. commercial health insurance database between 2009 and 2015. Use of TNFIs (infliximab, adalimumab, etanercept, golimumab and certolizumab pegol) and conventional-synthetic disease-modifying antirheumatic drugs (csDMARDs) was identified, and conditional logistic regression models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL. From a retrospective cohort of 55,446 adult patients, 101 NHL cases and 984 controls matched on age, gender and rheumatologic indication were included. Compared to controls, NHL cases had greater TNFI use (33% vs. 20%) but were similar in csDMARD use (70% vs. 71%). TNFI ever-use was associated with nearly two-fold increased risk of NHL (OR = 1.93; 95% CI: 1.16-3.20) with suggestion of increasing risk with duration (P-trend = 0.05). TNF fusion protein (etanercept) was associated with increased NHL risk (OR = 2.73; 95% CI: 1.40-5.33), whereas risk with anti-TNF monoclonal antibodies was not statistically significant (OR = 1.77; 95% CI: 0.87-3.58). In sensitivity analyses evaluating confounding by rheumatologic disease severity, channeling bias was not likely to account for our results. Our findings support the FDA black box warning for NHL. Continued surveillance and awareness of this rare but serious adverse outcome are warranted with new TNFIs and biosimilar products forthcoming.

Associations between statin use and risk of non-Hodgkin lymphomas by subtype.

Non-Hodgkin lymphomas (NHL) are a group of cancers with highly heterogeneous biology and clinical features. Statins are increasingly prescribed to prevent cardiovascular diseases. Early evidence shows a preventive effect of statins for some cancers, but their effect on NHL risk is unclear. We conducted a population-based nested case-control study involving 5,541 NHL cases and 27,315 controls matched for gender, age, place of residence and length of period of available prescription drug data. We assessed the use of statins prior to diagnosis (excluding the 12 months prior to the index date). We used conditional logistic regression models to estimate odds ratio (OR) and 95% confidence interval (CI) for use of any statin, adjusting for medical conditions, number of family physician visits for 5 years prior to index date, healthcare utilization, income and use of other medications. Over one-quarter of cases and controls were prescribed statins. Ever-use of any statin was associated with lower risk of Total NHL (OR = 0.82, 95% CI 0.76-0.89) and of certain subtypes including diffuse large B-cell lymphomas (DLBCL, OR = 0.77, 95% CI 0.65-0.92), plasma cell neoplasms (PCN, OR = 0.76, 95% CI 0.63-0.91) and other B-cell NHL (0.75, 0.59-0.95). Analysis by statin type suggested that the association was limited to high potency statin and lipophilic statin users. No clear duration or dose-response relationships were observed. Our findings provide evidence that statin use can reduce the risk of DLBCL and plasma cell lymphomas, but not other NHL types. Further studies are warranted to verify these associations and to examine the biological mechanisms.

Case-control investigation of occupational exposure to chlorinated solvents and non-Hodgkin's lymphoma.

OBJECTIVES: Although many studies have investigated the association between trichloroethylene (TCE) exposure and non-Hodgkin's lymphoma (NHL), less is known about other chlorinated solvents. We extended our previous analysis of occupational TCE exposure in a multicentre population-based case-control study of NHL to investigate associations with five additional chlorinated solvents: 1,1,1,-trichloroethane, carbon tetrachloride, chloroform, methylene chloride and perchloroethylene. METHODS: Cases (n=1189) and controls (n=982) provided detailed information on their occupational histories and workplace exposure to chlorinated solvents for selected occupations using job-specific interview modules. An industrial hygienist used this information and a review of the literature to assess occupational exposure to chlorinated solvents. We computed ORs and 95% CIs for different exposure metrics, with the unexposed group as the referent. We also computed ORs by NHL subtype. RESULTS: High cumulative hours exposed to carbon tetrachloride was associated with NHL (>520 hours: OR 1.9; 95% CI 1.0 to 3.6; Ptrend=0.04). This association remained after restricting to jobs with high-intensity exposure (OR 2.0; 95% CI 1.1 to 3.8; P=0.03) and ≥90% exposure probability (OR 2.1; 95% CI 1.0 to 4.3; P=0.03), adjusting for TCE (OR 2.1; 95% CI 1.0- to 4.1; P=0.04) and incorporating a 15-year lag (OR 1.9; 95% CI 1.0 to 3.6; P=0.06). The other evaluated chlorinated solvents were not associated with NHL. CONCLUSIONS: This is the first study using high-quality quantitative exposure assessment methods to identify a statistically significant elevated association between occupational exposure to carbon tetrachloride and NHL. Our findings, although limited by a small number of exposed cases, offer evidence that carbon tetrachloride may be a lymphomagen.

[Excess deaths for haematological tumours in Falconara Marittima (Marche Region, Central Italy): short story from the epidemiological survey up to now]. / EPICHANGE/3. Eccesso di morti per tumori ematologici a Falconara Marittima: breve storia dall'indagine epidemiologica a oggi.

API is a company refining petroleum products located in Falconara Marittima (Ancona Province, Marche Region, Central Italy). Thanks to the pressure made by citizens' committees, which considered the plant as a risk source for the population residing in the surroundings municipalities, Marche Region as institution asked for an epidemiological survey. This survey found a significative excess in deaths for haematological tumours in women and in a sub-group of retired and elderly. The results were published in one report and two scientific journals, and were also presented during a public meeting. It was urgent to made public health intervention, which were called for, but up to now nothing has been done. Here, the reconstruction of this affair, from the start of the epidemiological survey up to the more recent development in terms of public health.

[The opponent you do not just imagine. The case of Falconara Marittima (Marche Region, Central Italy)]. / EPICHANGE/2. L'avversario che non ti aspetti. Il caso di Falconara Marittima.

Falconara Marittima (Marche Region, Central Italy) is declared to be an area at high risk of environmental crisis, due to the presence of a refinery plant. In 2004, Marche Region funded an epidemiological survey to assess atmospheric risks linked to the refinery. This survey was conducted by the Italian National Cancer Institute of Milan, and citizens actively contributed. An excess for leukaemias and an increase in non-Hodgkin lymphomas were showed. These results were confirmed also by the Regional Environmental Protection Agency and the Regional Health Authority. But Marche Region and the Municipalities chose to not report the situation: the same Institutions, which at the beginning sided the citizens, became an opponent for health protection.

Comparison of hematological alterations and markers of B-cell activation in workers exposed to benzene, formaldehyde and trichloroethylene.

Benzene, formaldehyde (FA) and trichloroethylene (TCE) are ubiquitous chemicals in workplaces and the general environment. Benzene is an established myeloid leukemogen and probable lymphomagen. FA is classified as a myeloid leukemogen but has not been associated with non-Hodgkin lymphoma (NHL), whereas TCE has been associated with NHL but not myeloid leukemia. Epidemiologic associations between FA and myeloid leukemia, and between benzene, TCE and NHL are, however, still debated. Previously, we showed that these chemicals are associated with hematotoxicity in cross-sectional studies of factory workers in China, which included extensive personal monitoring and biological sample collection. Here, we compare and contrast patterns of hematotoxicity, monosomy 7 in myeloid progenitor cells (MPCs), and B-cell activation biomarkers across these studies to further evaluate possible mechanisms of action and consistency of effects with observed hematologic cancer risks. Workers exposed to benzene or FA, but not TCE, showed declines in cell types derived from MPCs, including granulocytes and platelets. Alterations in lymphoid cell types, including B cells and CD4+ T cells, and B-cell activation markers were apparent in workers exposed to benzene or TCE. Given that alterations in myeloid and lymphoid cell types are associated with hematological malignancies, our data provide biologic insight into the epidemiological evidence linking benzene and FA exposure with myeloid leukemia risk, and TCE and benzene exposure with NHL risk.

Iatrogenic immunosuppression and risk of non-Hodgkin lymphoma in solid organ transplantation: A population-based cohort study in Australia.

Iatrogenic immunosuppression is a strong risk factor for non-Hodgkin lymphoma (NHL) but the dose-related association between individual immunosuppressive agents and NHL risk is unknown. We conducted a population-based cohort study of 4131 adult Australian liver, heart and lung transplant recipients (1984-2006). We ascertained NHL incidence by probabilistic record linkage between transplant registries and the Australian Cancer Database, and abstracted risk factor data at transplantation and at regular intervals thereafter from medical records. We estimated adjusted hazard ratios (HR) for early (<1 year after transplantation; n = 29) and late (≥1 year; n = 61) NHL using the Fine and Gray proportional subdistribution hazards model that accounted for death as a competing risk. After adjustment for immunosuppression, the risk of both early and late NHL did not significantly differ by organ type. In final models, higher mean daily doses of azathioprine were associated with increased risk of both early [HR 2·20, 95% confidence interval (CI): 1·21-4·01] and late NHL (HR 1·78, 95% CI: 1·12-2·84). There was no association between any other maintenance immunosuppressive agent and NHL risk. This study provides evidence that differences in immunosuppression may explain variation in NHL incidence by organ type, and high doses of azathioprine may independently predict NHL risk.