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IntroductionOral health-related quality of life is a reflection of general health and wellbeing; related problems stand as major public health issues.

Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P< 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P= 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P< 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.

ObjectivesGiven 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.MethodsWe 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.ResultsWe 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.ConclusionsMost 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.

BackgroundNight shift work can disrupt circadian rhythm and cause chronic sleep deprivation, which might increase the risk of lymphoma through immunosuppression and oxidative stress.Material and methodsWe investigated the association between night shift work and risk of lymphoma subtypes in 867 incident cases and 774 controls, who participated in a multicentre Italian study between 2011 and 2017. Based on questionnaire information, occupational experts assessed the lifetime probability of night shift work, the total number of night shifts and years of night shift work among study participants. OR and 95% CI for lymphoma and its major subtypes associated with night shift work was calculated with logistic regression, adjusting by age, gender, education, study area, marital status and family history of haemolymphatic cancer.ResultsEver working night shifts was associated with an increase in the risk of chronic lymphocytic leukaemia (CLL) (OR 1.9, 95% CI 1.14 to 3.32), which was highest after a 15–34 years latency. However, there was not a linear increase in risk by probability of exposure, years of night shift work, nor lifetime number of night shifts whether under rotating or permanent work schedules. Risk of lymphoma overall, B cell lymphoma (BCL), its major subtypes other than CLL, and other less prevalent BCL subtypes combined did not show an association.ConclusionsWe found conflicting evidence of an association between night shift work and the risk of CLL. We did not observe an association with other lymphoma subtypes.

. The authors conducted a proportional mortality study of 1 043 deaths that occurred between 1956 and 1992 among men who used mainly dichloro-diphenyl-trichloroethane (DDT) in anti-malarial campaign in Sardinia, Italy, during the late 1940s. For each cause of interest, investigators compared observed deaths with expected deaths. The estimated DDT exposure ranged from 170 to 600 mg/[m.sup.3] in indoor operations and from 24 to 86 mg/[m.sup.3] in outdoor operations. Workers directly exposed to DDT had a significant increase in risk for liver and biliary tract cancers (PMR = 228; 95% confidence interval = 143, 345) and multiple myeloma (PMR = 341; 95% confidence interval = 110, 795). However, the PMR. for liver and biliary tract cancers was also elevated among workers who did not have direct occupational contact with DDT, and the authors observed no increase in either PMR, by number of days in exposed jobs. Perhaps DDT did not increase the risk or perhaps occupational exposure, although quite high, did not further increase the risk compared with the heavy baseline exposure of the entire Sardinian population, (ie., mainly through diet and drinking water). Expansion of the cohort to include all exposed workers, and collection of information to improve exposure assessment are needed to clarify these findings., IMMEDIATELY following World War II, the Rockefeller Foundation promoted and supported a campaign to eradicate malaria in Sardinia, Italy, where mortality from this disease was 5-6 times higher than in [...]

A case-control investigation of childhood acute lymphoblastic leukemia was conducted in the town of Carbonia (Sardinia, Italy). Parents of 9 cases diagnosed between 1980 and 1989 and 36 controls were interviewed at their respective residences. None of the risk factors analyzed was associated significantly with childhood acute lymphoblastic leukemia. The following were associated with an increased risk for childhood acute lymphoblastic leukemia: parents born outside of Carbonia, family history of cancer, alcohol consumption by fathers that exceeded 60 g/d, exposure of fathers to solvents at their workplaces, maternal smoking, use of antinausea medications during pregnancy, and presence of a well in the backyard. Chance and recall bias likely played a role in generating positive associations. The increases in childhood leukemia risk associated with the presence of a well and with use of antinausea medications during pregnancy are consistent with previous reports and require further investigation., SEVEN CASES of childhood acute lymphoblastic leukemia (cALL) occurred between 1983 and 1985 among children who lived in Carbonia, a town populated by 32 000 residents and located in southwestern [...]

Background: Some dietary factors have been associated with the risk of type 1 diabetes in childhood. Objective: We investigated relations between dietary energy from major food groups and incidence of childhood type 1 diabetes by using an ecologic study design. Design: We conducted univariate and multivariate regression analysis with incidence rates of type 1 diabetes in the late 1980s and early 1990s among children aged [is less than] 15 y in 40 countries as the dependent variable and average per capita daily intake of major food items and other socioeconomic, demographic, and geographic risk factors as the independent variables. Results: In the univariate regression model, per capita total energy intake was nonsignificantly associated with type 1 diabetes incidence (r = 0.31, NS), whereas energy from animal sources was associated (r = 0.61, P [is less than] 0.01) and energy from vegetal sources was inversely associated (r = -0.35, P [is less than] 0.05) with diabetes incidence. Among dietary items of animal origin, meat (r = 0.55, P [is less than] 0.001) and dairy products (r = 0.80, P [is less than] 0.0001) were predictors of elevated incidence rates, whereas among dietary items of vegetal origin, cereals (r = -0.64, P [is less than] 0.001) were inverse predictors. In the multivariate analysis, the inverse relation of diabetes incidence with energy from vegetables and the direct correlation with energy from animal sources explained the positive associations of type 1 diabetes incidence with geographic and socioeconomic covariates. Conclusion: The incidence of type 1 diabetes varied worldwide according to dietary patterns. In-depth exploration of dietary risk factors during pregnancy and early neonatal life is warranted to confirm whether and to what extent diet cooperates with genetic susceptibility in the early onset of type 1 diabetes. Am J Clin Nutr 2000;71:1525-9. KEY WORDS Cereals, energy intake, type 1 diabetes, meat, milk, nutrition, children

AbstractPurpose:To assess the predictive power of the comet assay in the context of occupational exposure to pesticides.Materials and methods:The recruited subjects completed a structured questionnaire and gave a blood sample. Exposure to pesticides was measured by means of an algorithm based on Dosemeci’s work (Agricultural Health Study). Approximately 50 images were analyzed for each sample via fluorescence microscopy. The extent of DNA damage was estimated by tail moment (TM) and is the product of tail DNA (%) and tail Length.Results:Crude significant risks (odds ratios, ORs) for values higher than the 75th percentile of TM were observed among the exposed subjects (score > 1). The frequency of some confounding factors (sex, age and smoking) was significantly higher among the exposed workers. A significant dose–effect relationship was observed between TM and exposure score. Significant high-risk estimates (ORs), adjusted by the studied confounding factors, among exposure to pesticides and TM, % tail DNA and tail length were confirmed using unconditional logistic regression models.Conclusions:The adjusted associations (ORs) between the comet parameters and exposure to pesticides were significant. The sensitivity of the comet test was low (41%), the specificity (89%) and the predictive positive value (0.77) were found acceptable.

ObjectivesTo investigate the association between occupational exposure to aromatic hydrocarbon solvents and risk of multiple myeloma (MM) in a large, consortium-based study.MethodsWe 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.ResultsBenzene, 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.ConclusionsOur 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.

•Fluctuations in fear of future violence are linked to both emotional exhaustion and cynicism at the within-person level.•Job control moderated the within-person relationship of fear of future violence with emotional exhaustion.•The relationship of future violence with emotional exhaustion was stronger for workers low in job control.•Employees with a greater sense of job control were less likely to translate fear of future violence into emotional exhaustion.

Background The epidemiology of myeloid hematologic malignancies in Italy has been poorly investigated.Methods We used a validated database of 1974-2003 incident cases of hematologic malignancies among the resident population (all ages) of Sardinia, Italy, to describe the incidence of myeloid malignancies overall (N = 4389 cases) and by subtype. We investigated the time trend of acute myeloid leukemia (N = 1227 cases), chronic myeloid leukemia (N = 613 cases), and myelodysplastic syndrome (N = 1296 cases), and used Bayesian methods to explore their geographic spread, and Poisson regression analysis to estimate their association with environmental and socio-economic factors.Results The annual standardized (world population) incidence rate (IR) of myeloid malignancies over the study period was 6.5 per 100,000 (95% CI 6.2-6.7). Myelodysplastic syndromes were the most prevalent subgroup (IR = 1.7, 95% CI 1.5-1.8). Incidence of all myeloid malignancies combined increased sharply during the study period with an annual percent change (APC) of 10.06% (95% CI 9.51-10.61), 19.77% for myelodysplastic syndromes (95% CI 19.63-19.91), and 3.18% (95% CI 2.99-3.37) for acute myeloid leukemia. Chronic myeloid leukemia did not show an upward trend. Apart from sporadic excesses in small rural communities and the major urban area, there was no evidence of spatial clustering. The risk of myeloid malignancies increased with increasing prevalence of sheep breeding.Conclusions Our results might prompt further research on the local genetic and environmental determinants of myeloid hematologic malignancies.

AbstractObjectives:1H NMR-metabolomic approach was used to investigate QTc interval correlation with plasma metabolic profiles in shiftworkers.Methods:Socio-demographic data, electrocardiographic QTc interval and plasma metabolic profiles from 32 male shiftworkers, were correlated by multivariate regression analysis.Results:We found a positive correlation between QTc interval values, body mass index, glycemia and lactate level and a negative correlation between QTc interval and both pyroglutamate and 3-hydroxybutyrate plasma level.Conclusions:Our analysis provides evidence of the association between clinical, metabolic profiles and QTc interval values. This could be used to identify markers of early effects and/or susceptibility in shiftworkers.

IntroductionThe association between ionising radiation and risk of solid tumours and leukaemia is well established; however, the role of low dose radiation exposure in the aetiology of lymphoma is still uncertain. We investigated the role of occupational exposure to internal and external ionising radiation in the aetiology of lymphoma and its major subtypes.MethodsBetween 1998 and 2004, 2348 cases and 2465 controls from six different European countries participated in the multicentre EpiLymph case-control study. A detailed occupational history was collected by questionnaire in all participants a coded using the ISCO68 occupational and NACE industrial coding systems. Based on the same coding systems, we developed a Job Exposure Matrix (JEM) to assess probability and intensity of exposure to internal and external ionising radiation. We used unconditional logistic regression to calculate Odds Ratios and their 95% Confidence Intervals for lymphoma and its major subtypes associated with the ionising radiation exposure metrics, adjusting by age, gender, education and country.ResultsRisk of lymphoma overall did not show an association with exposure to radiation either internal or external. Risk of Diffuse Large B-Cell Lymphoma (DLBCL) was elevated and did show an upward trend with intensity of exposure to external radiation (Low Intensity OR=2.1, 95%CI=0.97–4.46 and High Intensity OR=2.5, 95%CI=1.21–5.08). We did not observe any risk increase associated with internal exposure to ionising radiation.ConclusionsOur results provide limited support to the relation between external sources of ionising radiation and risk of DLBCL. We cannot exclude the possibility of bias due to the multiple comparisons we made.

Ultraviolet radiation (UVR) exposure has been inversely associated with Hodgkin lymphoma (HL) risk, but only inconsistently, only in a few studies, and without attention to HL heterogeneity. We conducted a pooled analysis of HL risk focusing on type and timing of UVR exposure and on disease subtypes by age, histology, and tumor-cell Epstein-Barr virus (EBV) status. Four case-control studies contributed 1320 HL cases and 6381 controls. We estimated lifetime, adulthood, and childhood UVR exposure and history of sunburn and sunlamp use. We used 2-stage estimation with mixed-effects models and weighted pooled effect estimates by inverse marginal variances. We observed statistically significant inverse associations with HL risk for UVR exposures during childhood and adulthood, sunburn history, and sunlamp use, but we found no significant dose-response relationships. Risks were significant only for EBV-positive HL (pooled odds ratio, 0.56; 95% confidence interval, 0.35 to 0.91 for the highest overall UVR exposure category), with a significant linear trend for overall exposure (P = .03). Pooled relative risk estimates were not heterogeneous across studies. Increased UVR exposure may protect against HL, particularly EBV-positive HL. Plausible mechanisms involving UVR induction of regulatory T cells or the cellular DNA damage response suggest opportunities for new prevention targets.

Many common genetic variants have been associated with non-Hodgkin lymphoma (NHL), but individual study results are often conflicting. To confirm the role of putative risk alleles in B-cell NHL etiology, we performed a validation genotyping study of 67 candidate single nucleotide polymorphisms within InterLymph, a large international consortium of NHL case-control studies. A meta-analysis was performed on data from 5633 B-cell NHL cases and 7034 controls from 8 InterLymph studies. rs3789068 in the proapoptotic BCL2L11 gene was associated with an increased risk for B-cell NHL (odds ratio = 1.21, P random = 2.21 × 10−11), with similar risk estimates for common B-cell subtypes. PRRC2A rs3132453 in the HLA complex class III region conferred a reduced risk of B-cell NHL (odds ratio = 0.68, P random = 1.07 × 10−9) and was likewise evident for common B-cell subtypes. These results are consistent with the known biology of NHL and provide insights into shared pathogenic components, including apoptosis and immune regulation, for the major B-cell lymphoma subtypes.

Many common genetic variants have been associated with non-Hodgkin lymphoma (NHL), but individual study results are often conflicting. To confirm the role of putative risk alleles in B-cell NHL etiology, we performed a validation genotyping study of 67 candidate single nucleotide polymorphisms within InterLymph, a large international consortium of NHL case-control studies. A meta-analysis was performed on data from 5633 B-cell NHL cases and 7034 controls from 8 InterLymph studies. rs3789068 in the proapoptotic BCL2L11gene was associated with an increased risk for B-cell NHL (odds ratio = 1.21, Prandom = 2.21 × 10−11), with similar risk estimates for common B-cell subtypes. PRRC2Ars3132453 in the HLA complex class III region conferred a reduced risk of B-cell NHL (odds ratio = 0.68, Prandom = 1.07 × 10−9) and was likewise evident for common B-cell subtypes. These results are consistent with the known biology of NHL and provide insights into shared pathogenic components, including apoptosis and immune regulation, for the major B-cell lymphoma subtypes.

Ethylene oxide, a high-volume commodity, is an established human carcinogen, although the relevant epidemiologic evidence is limited.

Some autoimmune disorders are increasingly recognized as risk factors for non-Hodgkin lymphoma (NHL) overall, but large-scale systematic assessments of risk of NHL subtypes are lacking. We performed a pooled analysis of self-reported autoimmune conditions and risk of NHL and subtypes, including 29 423 participants in 12 case-control studies. We computed pooled odds ratios (OR) and 95% confidence intervals (CI) in a joint fixed-effects model. Sjögren syndrome was associated with a 6.5-fold increased risk of NHL, a 1000-fold increased risk of parotid gland marginal zone lymphoma (OR = 996; 95% CI, 216-4596), and with diffuse large B-cell and follicular lymphomas. Systemic lupus erythematosus was associated with a 2.7-fold increased risk of NHL and with diffuse large B-cell and marginal zone lymphomas. Hemolytic anemia was associated with diffuse large B-cell NHL. T-cell NHL risk was increased for patients with celiac disease and psoriasis. Results for rheumatoid arthritis were heterogeneous between studies. Inflammatory bowel disorders, type 1 diabetes, sarcoidosis, pernicious anemia, and multiple sclerosis were not associated with risk of NHL or subtypes. Thus, specific autoimmune disorders are associated with NHL risk beyond the development of rare NHL subtypes in affected organs. The pattern of associations with NHL subtypes may harbor clues to lymphomagenesis.

Aims of our study were to explore whether and to what extent exposure to other lung carcinogens, or staging and clinical features of silicosis modify or confound the association between silica and lung cancer. We used data from a nested case-control study, conducted in the late 1980s in 29 Chinese mines and potteries (10 tungsten mines, 6 copper and iron mines, 4 tin mines, 8 pottery factories, and 1 clay mine), that included 316 lung cancer cases and 1,356 controls, matched by decade of birth and facility type. The previous analysis of these data presented results by type of mine or factory. In our study, pooling all 29 Chinese work sites, lung cancer risk showed a modest association with silica exposure. Risk did not vary after excluding subjects with silicosis or adjusting the risk estimates by radiological staging of silicosis. Strong correlation among exposures prevented a detailed evaluation of the role of individual exposures. However, lung cancer risk was for the most part absent when concomitant exposure to other workplace lung carcinogens, such as polycyclic aromatic hydrocarbons (PAHs), nickel or radon-daughters, was considered. The cross classification of lung cancer risk by categories of exposure to respirable silica and total respirable dust did not show an independent effect of total respirable dust. Silicosis showed a modest association with lung cancer, which did not vary by severity of radiological staging, or by radiological evidence of disease progression, or by level of silica exposure. However, among silicotic subjects, lung cancer risk was significantly elevated only when exposure to cadmium and PAH had occurred. Our results suggest that, among silica-exposed Chinese workers, numerous occupational and non-occupational risk factors interact in a complex fashion to modify lung cancer risk. Future epidemiological studies on silica and lung cancer should incorporate detailed information on exposure to other workplace lung carcinogens, total respirable dust, and on surface size and age of silica particles to understand whether and to what extent they affect the carcinogenic potential of silica. Am. J. Ind. Med. 40:674–682, 2001. © 2001 Wiley-Liss, Inc

Organic solvents have been associated with renal cell cancer; however, the risk by gender and type of solvents is unclear. We evaluated the risk of renal cell carcinoma among men and women exposed to all organic solvents-combined, all chlorinated aliphatic hydrocarbons (CAHC)-combined, and nine individual CAHC using a priori job exposure matrices developed by NCI in a population-based case-control study in Minnesota, U.S. We interviewed 438 renal cell cancer cases (273 men and 165 women) and 687 controls (462 men and 225 women). Overall, 34% of male cases and 21% of female cases were exposed to organic solvents in general. The risk of renal cell carcinoma was significantly elevated among women exposed to all organic solvents combined (OR = 2.3; 95% CI = 1.3–4.2), to CAHC combined (OR = 2.1; 95% CI = 1.1–3.9), and to trichloroethylene (TCE) (OR = 2.0; 95% CI = 1.0–4.0). Among men, no significant excess risk was observed among men exposed to any of these nine individual CAHCs, all CAHCs-combined, or all organic solvents-combined. These observed gender differences in risk of renal cell carcinoma in relation to exposure to organic solvents may be explained by chance based on small numbers, or by the differences in body fat content, metabolic activity, the rate of elimination of xenobiotics from the body, or by differences in the level of exposure between men and women, even though they have the same job title. Am. J. Ind. Med. 36:54–59, 1999. Published 1999 Wiley-Liss, Inc.

In a recent report, we found an elevated risk of cancer of the central nervous system (CNS) in several occupations and industries, and a modest association with exposure to solvents and to contact with the public. To further explore the occupational risk of CNS cancer among women, we extended the analysis of the previous death certificate-based case-control study, including 12,980 female cases (ICD-9 codes 191 and 192) in 24 US states in 1984–1992 and 51,920 female controls who died from diseases other than malignancies and neurological disorders. We applied newly designed job-exposure matrices for 11 occupational hazards, previously reported as brain cancer risk factors, to the occupation and industry codes in the death certificates. We also conducted a separate analysis of 161 meningioma cases (ICD-9 codes 192.1 and 192.3), a tumor more frequent among women, particularly in the postmenopausal age group. Overall, CNS cancer risk showed a 20–30% increase among women exposed to electromagnetic fields (EMF), methylene chloride, insecticides and fungicides, and contact with the public. Risk for meningioma was elevated among women exposed to lead (OR = 1.9; 95% CI 1.0, 3.9). CNS cancer did not show a clear pattern of risk increase by probability and intensity of exposure to any of the explored risk factors. Cross-classification by probability and intensity of exposure did not reveal any significant trend. Cases were too few to explore trends of meningioma by probability and intensity of exposure to lead. We did not find evidence of a strong contribution of 11 occupational hazards to the etiology of CNS cancer. However, limitations of the occupational information might have reduced our ability to detect clear patterns of risk. Am. J. Ind. Med. 36:70–74, 1999. © 1999 Wiley-Liss, Inc.

Because of the rarity of peritoneal mesothelioma, occupational risks associated with it have seldom been studied, particularly among women. In this respect, death certificates databases may provide numbers large enough for analysis, although the International Classification of Diseases, 9th revision (ICD-9) does not single out mesothelioma from the rest of peritoneal cancers. The aim of this paper is twofold: to explore occupational risks of peritoneal cancer among men and women, and to test the performance of a job-exposure matrix in detecting its association with asbestos exposure using the occupation and industry reported in the death certificate. From a large database containing information on the 1984–1992 death certificates of 24 U.S. states, we identified 657 deaths from peritoneal cancer and 6,570 controls who died from non-malignant diseases, 1:10 matched by region, gender, race, and 5-year age group. Occupations at risk included insulators among men, and machine operators among women. Among men, we found a significant increase in risk associated with employment in manufacturing industries, such as industrial and miscellaneous chemicals; miscellaneous non-metallic mineral and stone products; construction and material handling machines; and electrical machinery, equipment, and supplies; as well as in services to dwellings and other buildings. Industries at increased risk among women included elementary and secondary schools; miscellaneous retail stores; and publishing and printing. Our job-exposure matrix classified 17 male cases and 3 controls in the high probability category of exposure to asbestos (OR = 61.6). Among men, risk of peritoneal cancer increased significantly by probability and intensity of exposure to asbestos. No such pattern was observed among women. The job-exposure matrix did not classify any female subjects in the high probability or intensity of asbestos exposure. This study provides evidence that death certificate data and job-exposure matrices are useful tools to observe well-established associations, such as the one existing between peritoneal cancer and asbestos exposure among men, in spite of crude information, disease misclassification, and occupational misclassification. These factors are more likely to preclude meaningful results among women. Am. J. Ind. Med. 35:9–14, 1999. Published 1999 Wiley-Liss, Inc.

The objective of this study was to test the hypothesis of a lower mortality from cancer and cardiovascular diseases among men expressing glucose-6-phosphate dehydrogenase (G6PD) deficiency. We designed a mortality study based on death certificates from January 1, 1982 through December 31, 1992 in a cohort of G6PD-deficient men. Cohort members were 1,756 men, identified as expressing the G6PD-deficient phenotype during a 1981 population screening of the G6PD polymorphism. The setting was the island of Sardinia, Italy. Outcome measures were cause-specific standardized mortality ratios (SMRs), which were computed as 100 times the observed/expected ratio, with the general Sardinian male population as the reference. Deaths from all causes were significantly less than expected due to decreased SMRs for ischemic heart disease (SMR, 28; 95% confidence interval [CI], 10 to 62), cerebrovascular disease (SMR, 22; 95% CI, 6 to 55), and liver cirrhosis (SMR, 12; 95% CI, 0 to 66), which explained 95.6% of the deficit in total mortality. All cancer mortality was close to the expectation, with a significant increase in the SMR for non-Hodgkin's lymphoma (SMR, 545; 95% CI, 147 to 1,395). A decrease in mortality from cardiovascular diseases was one of the study hypotheses, based on an earlier human report and experimental evidence. However, selection bias is also a likely explanation. Further analytic studies are warranted to confirm whether subjects expressing the G6PD-deficient phenotype are protected against ischemic heart disease and cerebrovascular disease. This cohort study is consistent with more recent case-control studies in rejecting the hypothesis of a decreased cancer risk among G6PD-deficient subjects. The observed increase in mortality from non-Hodgkin's lymphoma and decrease in mortality from liver cirrhosis were not previously reported.

Objectives: The etiology of male breast cancer is obscure, although an excess risk has been associated with Klinefelter syndrome, testicular disorders, benign breast disease including gynecomastia, use of exogenous estrogens, radiation, and a family history of male or female breast cancer. We conducted a case-control study to investigate risk factors further for breast cancer in men. Methods: Based on data from the 1986 National (United States) Mortality Followback Survey (NMFS) of almost 20,000 deceased adults (age 25 years or over), we compared information obtained from next-of-kin interviews of 178 men who died of breast cancer with that of 512 male controls who died of other causes. Information was obtained on selected demographic and other factors, including diet, exercise, occupation, height and weight, and use of tobacco and alcohol. Results: Increased risks were found for men who were described by their next-of-kin as very overweight (odds ratio [OR] = 2.3, 95 percent confidence interval [CI] = 1.1-5.0). The risks associated with the three upper quartiles of body mass index (BMI) (wt/ht2) were 1.3, 1.6, and 2.3, respectively, with a significant dose-response relationship (P < 0.01). An excess risk was also associated with limited exercise (OR = 1.3, CI = 0.8-2.0). Consumption of red meat was associated with an increased risk, and consumption of fruits and vegetables with a decreased risk, although the trends were not significant. No association was found for tobacco or alcohol use, but an excess risk was associated with higher levels of socioeconomic status (SES) (OR = 1.8, CI = 1.1-3.0). Conclusions: Our study suggests that obesity increases the risk of male breast cancer, possibly through hormonal mechanisms, while dietary factors, physical activity, and SES indicators also deserve further investigation. Cancer Causes andd Control 1998, 269-275

We tested the impact of three features of a job-exposure matrix on risk estimates in a case-control study that evaluated the association of methylene chloride and astrocytic brain cancer. These features were probability of use of the agent; the consideration of decade of predominant use of methylene chloride within each occupation; and the use of a more specific industrial-occupational coding system. We compared the risk estimates obtained with and without these features. The introduction of each feature had a striking effect on the estimate of relative risk. The odds ratio ranged from 1.47 with none of these features, to 2.47 with high probability of exposure within industry and occupation, to 4.15 with high probability of exposure and specific industrial-occupational coding, to 6.08 with the three features together. These results indicate that the degree of exposure misclassification can be reduced by the introduction of these features into the job-exposure matrix.

The risk of cancer of the central nervous system (CNS) by industry and occupation was investigated with a case-control analysis of the death certificates of 28,416 cases and 113,664 controls, selected from over 4.5 million deaths in 24 U.S. states between 1984 and 1992. Industries showing consistent increases in risk by gender and race included textile mills, paper mills, printing and publishing industries, petroleum refining, motor vehicles manufacturing, telephone and electric utilities, department stores, health care services, elementary and secondary schools, and colleges and universities. CNS cancer risk was increased for administrators in education and related fields, secondary school teachers, and other education- and health-related occupations. The application of job-exposure matrices to the industry/occupation combinations revealed a modest increase in risk for potential contact with the public at work and exposure to solvents. Occupational exposure to electromagnetic fields (EMF) was not associated with CNS cancer, although an association was observed with a few EMF-related occupations and industries. Agricultural exposures were associated with significant risk increases among white women and white men. Further work is required to investigate in more detail specific occupational exposures or possible confounders responsible for the observed associations. Am. J. Ind. Med. 33:247–255, 1998. © 1998 Wiley-Liss, Inc.

A hospital based case-control study was conducted to test the hypothesis of a lower lung cancer risk in G6PD-deficient subjects. Cases were 156 male patients with lung cancer, admitted to « Binaghi » Hospital, Local Health Unit (USL) 20, Cagliari (Italy), between January 1984 and November 1986. Controls were 235 male patients, admitted to the same hospital In the same time period, for diseases other than cancer (all types) and hemolytic anemia. No decrease of the lung cancer risk was found in G6PD-deficient subjects. This result, in line with recent reports in the literature, suggests that the genetic condition of G6PD deficiency does not provide significant protection against the development of lung cancer in humans.

The authors examine the problems of planning and conducting a multicentric case-control study on diet and gastric cancer in Italy. The solutions chosen for the study design, cases and controls identification, dietary interview, production of a common protocol for the field work are discussed. Results on the evaluation of the quality and comparability of collected data are presented. Further, compliance of cases and controls to the interview and to the blood and urine sampling with reasons of non-response are shown. Finally, the phases of the study and the methods for improving and controlling omogeneity among Centers are summarized.

Occupational associations with gastric cancer were investigated in a multicenter case-control study in Italy involving interviews with 640 histologically confirmed male cases and 959 controls, randomly selected from the resident populations of the study areas. From information on the three jobs each person held the longest, risks were evaluated according to employment in 35 occupations (ever or 21+ years) and to estimated exposure (ever or 21+ years) to six chemicals using a job-exposure matrix. All risk estimates were adjusted by personal, demographic, and dietary variables identified as gastric-cancer risk factors in previous analyses. The only significantly increased risk was observed for sailors, seamen, and allied groups (ever employed: odds ratio [OR]=2.9; 95 percent confidence interval [CI]=1.1–8.0; 21+ years: OR=3.1, CI=0.8–13). Nonsignificant increases after 21+ years of employment were observed for forestry workers, miners, and janitors and cleaners. Crude ORs were elevated significantly among farmers, but adjusting for demographic and lifestyle factors largely eliminated the association: a nonsignificant 30 percent excess risk remained for farm laborers, but there was no rise in risk among long-term farm laborers and no excess among farm owners. Application of the job-exposure matrix revealed excess risks of borderline significance associated with potential exposure to mineral dusts and nitrogen oxides. For subjects with 21+ years of potential exposure, nonsignificantly increased risks were related to mineral dusts, asbestos, fertilizers, and nitrosamines. Although possibly incomplete occupational histories and use of broad occupational codes likely resulted in some exposure misclassification, the results of this study indicate that occupation in general is not a strong risk factor for gastric cancer. The findings, however, are consistent with previous reports suggesting that certain occupational exposures may influence gastric cancer risk.

Aims and Background Evidence linking the glucose-6-phosphate dehydrogenase (G6PD) polymorphism and risk of non-Hodgkin's lymphoma is conflicting. Risk of non-Hodgkin's lymphoma was increased in subjects expressing the G6PD deficient phenotype, whereas subjects under medication with statins, a lipid-lowering class of drugs partially mimicking G6PD deficiency, seemed to enjoy a protective effect.Methods We conducted a case-control study on lymphoma risk associated with the self-reported G6PD deficient phenotype in 122 lymphoma male cases and 116 male controls in Sardinia, Italy. The association with the GdMed+ genotype, the most frequent variant expressing a deficient enzyme activity, was also tested in 49 male lymphoma cases and 31 controls. The WHO classification was used to identify lymphoma subentities.Results Neither self-reported G6PD deficient phenotype nor the GdMed+ genotype showed an association with lymphoma risk or its subentities.Conclusions Our results do not confirm an association either positive or negative between the G6PD polymorphism and lymphoma risk.

We tested the hypothesis of an association between childhood type 1 diabetes (T1D) risk and nitrate concentration in drinking water in Sardinia, Italy, using Poisson regression analysis. Childhood T1D risk showed an inverse trend with increasing quartile of nitrate level in the total population and among men. A nitrate concentration in drinking water below 10 mg/l is unlikely to account for the spatial variation in childhood T1D incidence.We tested the hypothesis of an association between childhood type 1 diabetes (T1D) risk and nitrate concentration in drinking water in Sardinia, Italy, using Poisson regression analysis. Childhood T1D risk showed an inverse trend with increasing quartile of nitrate level in the total population and among men. A nitrate concentration in drinking water below 10 mg/l is unlikely to account for the spatial variation in childhood T1D incidence.

Abstract: Objective: To discuss regulatory guidelines excluding subjects with erythrocyte glucose-6-phosphate dehydrogenase (G6PD) deficiency from lead-exposed jobs in the light of epidemiology findings on the mortality of these subjects. Methods: Two mortality follow-up studies were conducted. The first comprised 1979 male subjects newly identified as G6PD-deficient during a 1981 screening of the G6PD polymorphism among the general population in Sardinia, Italy. The second comprised 1080 male workers employed in maintenance and production departments of a lead smelting plant, who were divided into two subcohorts by erythrocyte G6PD phenotype. Results: As compared with the general male population, G6PD-deficient subjects had significantly fewer deaths than expected from ischemic heart disease (standardized mortality ratio (SMR)=28; 95% CI 10–62), cerebrovascular diseases (SMR=22; 95% CI 6–55), and liver cirrhosis (SMR = 12; 95% CI 0–66). Among lead smelters the standardized mortality rates from cardiovascular diseases and all cancers observed among the G6PD-deficient subcohort were lower than those seen among subjects with the wild-type G6PD. No death from disease of the blood and hematopoietic system was observed among G6PD-deficient subjects in these two follow-up studies. Conclusions: These studies did not provide evidence of hypersensitivity to lead hematotoxicity among G6PD-deficient individuals at exposure levels within the current standards. Provided that workplace exposure complies with current standards, the hypothetical benefit of excluding G6PD-deficient individuals from lead-exposed jobs should be weighted against the loss of personal abilities and the economic damage in a social environment with diffuse unemployment.

Checking the resident 1,868 males found to be G6PD deficient out of 15,964 examined, we observed the percentage of G6PD deficiency in male population largely varying among the various Sardinian towns ranging from 1 to over 50%. As preliminary analysis, in 24 towns out of 39 in which the sample was sufficiently suggestive of their whole resident male population, we calculated Standardized Mortality Rates (SMR) for all cancers and linear regression between SMRs and frequency of G6PD deficiency in the same towns. Previous observations suggested the hypothesis of a negative correlation between frequency of G6PD deficiency and incidence of cancer, as we found in the preliminary analysis of this study. The results are not sufficient either to accept or to refuse this hypothesis.

BackgroundDetecting new disease-exposure associations is an important public health issue. We created a pilot network (MAREL - MAlattie e Rischi Emergenti sul Lavoro) of occupational disease consultation centres of Italian university hospitals to which patients are referred for potentially work-related diseases.MethodsThe MAREL network currently includes five occupational disease consultation centres of university hospitals located in central-northern Italy. Patients are referred to these consultation centres by their general practitioners, occupational physicians or other specialists for the investigation of the putative occupational origin of the disease. Each centre collects cases of putative occupational origin through a structured and standardised data collection form. We collect data on: diagnosis; personal habits; occupational history; exposure assessment for potentially associated risk factors; physician’s opinion on the possible causal relationship between disease and occupation. Data are coded according to national and international classifications.ResultsThe data collection started in 2016. We collected 1516 cases of putative occupational diseases. Intervertebral lumbar disc degeneration was the most represented condition (n=170, 11.2%). Apart from musculoskeletal disorders, cases of asthma were the most frequently reported (n=59, 3.9%). About 11% of patients were construction workers. The most frequently reported exposures were: manual material handling (29.5%, out of 1811), hand-arm vibrations (13.9%), and repetitive movements of the upper limb (10.9%).DiscussionThe MAREL network will be expanded to other occupational disease consultation centres in 2017 with the aim to contribute to already existing surveillance systems (i.e. MALPROF) by the detection of new and emerging occupational diseases and risks.

Aim and background Public concern on an increased incidence of childhood leukemia in SW Sardinia prompted the authors to an epidemiological investigation.Methods Incident childhood neoplasms observed in the Cagliari province (Sardinia - Italy) in 1974-1989 were registered. Expected cases of the most frequent childhood cancers were calculated for each town, based on the sex-and age-specific incidence rates in the province.Results An excess risk of childhood acute lymphoblastic leukemia (ALL) was observed in Carbonia, a town located in the SW part of the province. The risk was highest in 1983-85, when 7 cases occurred versus 0.8 expected (RR = 8.7; 95 % C.I. = 4.6, 16.3). No spatial clustering of ALL cases was observed within the town.Conclusions A significantly higher than expected incidence of childhood ALL was observed in the town of Carbonia in 1983-85. In alternative to chance, possible exposure to environmental pollutants from a near industrial settlement is discussed as the cause of the observed excess, but it is far to be proven. Other hypotheses, including a viral infection in a population with increased susceptibility, as suggested for new urban settlements, cannot be discarded.

Background Non-Hodgkin lymphoma (NHL), the most common hematologic malignancy, consists of numerous subtypes. The etiology of NHL is incompletely understood, and increasing evidence suggests that risk factors may vary by NHL subtype. However, small numbers of cases have made investigation of subtype-specific risks challenging. The International Lymphoma Epidemiology Consortium therefore undertook the NHL Subtypes Project, an international collaborative effort to investigate the etiologies of NHL subtypes. This article describes in detail the project rationale and design. Methods We pooled individual-level data from 20 case-control studies (17471 NHL cases, 23096 controls) from North America, Europe, and Australia. Centralized data harmonization and analysis ensured standardized definitions and approaches, with rigorous quality control. Results The pooled study population included 11 specified NHL subtypes with more than 100 cases: diffuse large B-cell lymphoma (N = 4667), follicular lymphoma (N = 3530), chronic lymphocytic leukemia/small lymphocytic lymphoma (N = 2440), marginal zone lymphoma (N = 1052), peripheral T-cell lymphoma (N = 584), mantle cell lymphoma (N = 557), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (N = 374), mycosis fungoides/Sézary syndrome (N = 324), Burkitt/Burkitt-like lymphoma/leukemia (N = 295), hairy cell leukemia (N = 154), and acute lymphoblastic leukemia/lymphoma (N = 152). Associations with medical history, family history, lifestyle factors, and occupation for each of these 11 subtypes are presented in separate articles in this issue, with a final article quantitatively comparing risk factor patterns among subtypes. Conclusions The International Lymphoma Epidemiology Consortium NHL Subtypes Project provides the largest and most comprehensive investigation of potential risk factors for a broad range of common and rare NHL subtypes to date. The analyses contribute to our understanding of the multifactorial nature of NHL subtype etiologies, motivate hypothesis-driven prospective investigations, provide clues for prevention, and exemplify the benefits of international consortial collaboration in cancer epidemiology.

Background Marginal zone lymphoma (MZL), comprised of nodal, extranodal, and splenic subtypes, accounts for 5%–10% of non-Hodgkin lymphoma cases. A detailed evaluation of the independent effects of risk factors for MZL and its subtypes has not been conducted. Methods Data were pooled from 1052 MZL cases (extranodal [EMZL] = 633, nodal [NMZL] = 157, splenic [SMZL] = 140) and 13766 controls from 12 case–control studies. Adjusted unconditional logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs). Results Novel findings for MZL subtypes include increased risk for B-cell activating autoimmune conditions (EMZL OR = 6.40, 95% CI = 4.24 to 9.68; NMZL OR = 7.80, 95% CI = 3.32 to 18.33; SMZL OR = 4.25, 95% CI = 1.49 to 12.14), hepatitis C virus seropositivity (EMZL OR = 5.29, 95% CI = 2.48 to 11.28), self-reported peptic ulcers (EMZL OR = 1.83, 95% CI = 1.35 to 2.49), asthma without other atopy (SMZL OR = 2.28, 95% CI = 1.23 to 4.23), family history of hematologic cancer (EMZL OR = 1.90, 95% CI = 1.37 to 2.62) and of non-Hodgkin lymphoma (NMZL OR = 2.82, 95% CI = 1.33 to 5.98), permanent hairdye use (SMZL OR = 6.59, 95% CI = 1.54 to 28.17), and occupation as a metalworker (NMZL OR = 3.56, 95% CI = 1.67 to 7.58). Reduced risks were observed with consumption of any alcohol (EMZL fourth quartile OR = 0.48, 95% CI = 0.28 to 0.82) and lower consumption of wine (NMZL first to third quartile ORs < 0.45) compared with nondrinkers, and occupation as a teacher (EMZL OR = 0.58, 95% CI = 0.37 to 0.88). Conclusion Our results provide new data suggesting etiologic heterogeneity across MZL subtypes although a common risk of MZL associated with B-cell activating autoimmune conditions was found.

Background Mycosis fungoides and Sézary syndrome (MF/SS) are rare cutaneous T-cell lymphomas. Their etiology is poorly understood. Methods A pooled analysis of 324 MF/SS cases and 17217 controls from 14 case–control studies from Europe, North America, and Australia, as part of the International Lymphoma Epidemiology Consortium (InterLymph) Non-Hodgkin Lymphoma (NHL) Subtypes Project, was carried out to investigate associations with lifestyle, medical history, family history, and occupational risk factors. Multivariate logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI). Results We found an increased risk of MF/SS associated with body mass index equal to or larger than 30kg/m2 (OR = 1.57, 95% CI = 1.03 to 2.40), cigarette smoking for 40 years or more (OR = 1.55, 95% CI = 1.04 to 2.31), eczema (OR = 2.38, 95% CI = 1.73 to 3.29), family history of multiple myeloma (OR = 8.49, 95% CI = 3.31 to 21.80), and occupation as crop and vegetable farmers (OR = 2.37, 95% CI = 1.14 to 4.92), painters (OR = 3.71, 95% CI = 1.94 to 7.07), woodworkers (OR = 2.20, 95% CI = 1.18 to 4.08), and general carpenters (OR = 4.07, 95% CI = 1.54 to 10.75). We also found a reduced risk of MF/SS associated with moderate leisure time physical activity (OR = 0.46, 95% CI = 0.22 to 0.97). Conclusions Our study provided the first detailed analysis of risk factors for MF/SS and further investigation is needed to confirm these findings in prospective data and in other populations.

Background Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are two subtypes of non-Hodgkin lymphoma. A number of studies have evaluated associations between risk factors and CLL/SLL risk. However, these associations remain inconsistent or lacked confirmation. This may be due, in part, to the inadequate sample size of CLL/SLL cases. Methods We performed a pooled analysis of 2440 CLL/SLL cases and 15186 controls from 13 case-control studies from Europe, North America, and Australia. We evaluated associations of medical history, family history, lifestyle, and occupational risk factors with CLL/SLL risk. Multivariate logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results We confirmed prior inverse associations with any atopic condition and recreational sun exposure. We also confirmed prior elevated associations with usual adult height, hepatitis C virus seropositivity, living or working on a farm, and family history of any hematological malignancy. Novel associations were identified with hairdresser occupation (OR = 1.77, 95% CI = 1.05 to 2.98) and blood transfusion history (OR = 0.79, 95% CI = 0.66 to 0.94). We also found smoking to have modest protective effect (OR = 0.9, 95% CI = 0.81 to 0.99). All exposures showed evidence of independent effects. Conclusions We have identified or confirmed several independent risk factors for CLL/SLL supporting a role for genetics (through family history), immune function (through allergy and sun), infection (through hepatitis C virus), and height, and other pathways of immune response. Given that CLL/SLL has more than 30 susceptibility loci identified to date, studies evaluating the interaction among genetic and nongenetic factors are warranted.

Background Non-Hodgkin lymphoma (NHL) comprises biologically and clinically heterogeneous subtypes. Previously, study size has limited the ability to compare and contrast the risk factor profiles among these heterogeneous subtypes. Methods We pooled individual-level data from 17 471 NHL cases and 23 096 controls in 20 case–control studies from the International Lymphoma Epidemiology Consortium (InterLymph). We estimated the associations, measured as odds ratios, between each of 11 NHL subtypes and self-reported medical history, family history of hematologic malignancy, lifestyle factors, and occupation. We then assessed the heterogeneity of associations by evaluating the variability (Q value) of the estimated odds ratios for a given exposure among subtypes. Finally, we organized the subtypes into a hierarchical tree to identify groups that had similar risk factor profiles. Statistical significance of tree partitions was estimated by permutation-based P values (P NODE). Results Risks differed statistically significantly among NHL subtypes for medical history factors (autoimmune diseases, hepatitis C virus seropositivity, eczema, and blood transfusion), family history of leukemia and multiple myeloma, alcohol consumption, cigarette smoking, and certain occupations, whereas generally homogeneous risks among subtypes were observed for family history of NHL, recreational sun exposure, hay fever, allergy, and socioeconomic status. Overall, the greatest difference in risk factors occurred between T-cell and B-cell lymphomas (P NODE < 1.0×10−4), with increased risks generally restricted to T-cell lymphomas for eczema, T-cell-activating autoimmune diseases, family history of multiple myeloma, and occupation as a painter. We further observed substantial heterogeneity among B-cell lymphomas (P NODE < 1.0×10−4). Increased risks for B-cell-activating autoimmune disease and hepatitis C virus seropositivity and decreased risks for alcohol consumption and occupation as a teacher generally were restricted to marginal zone lymphoma, Burkitt/Burkitt-like lymphoma/leukemia, diffuse large B-cell lymphoma, and/or lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. Conclusions Using a novel approach to investigate etiologic heterogeneity among NHL subtypes, we identified risk factors that were common among subtypes as well as risk factors that appeared to be distinct among individual or a few subtypes, suggesting both subtype-specific and shared underlying mechanisms. Further research is needed to test putative mechanisms, investigate other risk factors (eg, other infections, environmental exposures, and diet), and evaluate potential joint effects with genetic susceptibility.

Background Follicular lymphoma (FL) has been linked with cigarette smoking and, inconsistently, with other risk factors. Methods We assessed associations of medical, hormonal, family history, lifestyle, and occupational factors with FL risk in 3530 cases and 22639 controls from 19 case–control studies in the InterLymph consortium. Age-, race/ethnicity-, sex- and study-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression. Results Most risk factors that were evaluated showed no association, except for a few modest or sex-specific relationships. FL risk was increased in persons: with a first-degree relative with non-Hodgkin lymphoma (OR = 1.99; 95% CI = 1.55 to 2.54); with greater body mass index as a young adult (OR = 1.15; 95% CI = 1.04 to 1.27 per 5kg/m2 increase); who worked as spray painters (OR = 2.66; 95% CI = 1.36 to 5.24); and among women with Sjögren syndrome (OR = 3.37; 95% CI = 1.23 to 9.19). Lower FL risks were observed in persons: with asthma, hay fever, and food allergy (ORs = 0.79–0.85); blood transfusions (OR = 0.78; 95% CI = 0.68 to 0.89); high recreational sun exposure (OR = 0.74; 95% CI = 0.65 to 0.86, fourth vs first quartile); who worked as bakers or millers (OR = 0.51; 95% CI = 0.28 to 0.93) or university/higher education teachers (OR = 0.58; 95% CI = 0.41 to 0.83). Elevated risks specific to women included current and longer duration of cigarette use, whereas reduced risks included current alcohol use, hay fever, and food allergies. Other factors, including other autoimmune diseases, eczema, hepatitis C virus seropositivity, hormonal drugs, hair dye use, sun exposure, and farming, were not associated with FL risk. Conclusions The few relationships observed provide clues suggesting a multifactorial etiology of FL but are limited in the extent to which they explain FL occurrence.

Thalassemia is an inherited blood disease characterized by low levels or absence of normal globin chains. Severe forms of thalassemia, thalassemia major (TM), require regular blood transfusions, the main cause of secondary hemosyderosis. However, iron overload is a potential complication, even in patients (pts) with thalassemia intermedia (TI), who do not require transfusions. Among them, iron overload is mainly the result of an excessive absorption of dietary iron, caused by a down-regulation of hepcidin, an hepatic hormone that acts as a major regulator of systemic iron homeostasis. Very low mRNA levels of hepcidin have been reported in urine as well as in liver biopsies from patients with TI. It has been also reported that, interleukin-1 alpha (IL-1α) stimulates hepcidin transcription, raising the question as to whether a down-regulation of this cytokine may be responsible, at least partially, for the excessive iron absorption occurring in patients with TI. Here, we assessed whether IL-1α was involved in hepcidin regulation in β-thalassemia. Peripheral blood mononuclear cells (PBMCs) were isolated from 6 TM pts, 8 TI pts and 6 controls. mRNA was obtained from PBMCs by RT-PCR. Hepcidin mRNA levels were reduced in both TM and TI pts when compared to the age matched normal controls. Neverthless, hepcidin mRNA levels were significantly lower in TI pts, as compared to TM pts receiving regular blood transfusions. Among TI pts lower hepcidin mRNA level was associated with lower level of IL-α. Tumor necrosis factor alpha (TNF-α) does not seem to be involved in the regulation of hepcidin transcription. Interestingly, the levels of mRNA expression of acyl-CoA-cholesterol acyltransferase (ACAT), the enzyme responsible for intracellular cholesterol ester accumulation, and thus, for atherosclerotic plaque formation were strongly induced in PBMCs in TI pts. These results suggest that PBMCs hepcidin and IL-1-α measurements could possibly be used in the future as simple, ease and sensible diagnostic tools for the detection of iron overload in patients with thalassemia. ACAT expression may even be used as therapeutic target in preventing atherosclerotic complications such as pulmonary thromboembolism, cerebral thrombosis, and leg ulcers. frequently occurring in such patients.