Occupational exposure to gasoline and the risk of non-Hodgkin lymphoma: A review and meta-analysis of the literature

AimsGasoline comprises over 500 chemicals, including the known or suspected carcinogens benzene, 1,3-butadiene, ethylbenzene and methyl tert-butyl ether (MTBE). To assess whether work in the production, distribution and use of gasoline is associated with non-Hodgkin lymphoma (NHL), we reviewed the published literature on this topic. Method: English-language peer-reviewed articles were identified by keyword searches of bibliographic databases. Twenty-two cohorts and thirteen case–control studies examined the risk of NHL among persons employed in the downstream petroleum industry. Result: No positive associations were found with the exception of one study. The pooled risk estimate from a random-effects meta-analysis was 1.02 (95% confidence interval (CI) 0.94–1.12). Although there were no estimates available, exposure is likely to have varied by occupation, location and time period; there was no evidence however that risk estimates varied by any of these factors. NHL is a heterogeneous disease, yet no data were reported for NHL subtypes. Conclusion: In summary, there is no suggestion across an extensive literature that exposure to gasoline at the levels workers’ experience in an occupational setting increases the risk of NHL.     

Exposure to Fluoride in Drinking Water and Hip Fracture Risk: A Meta-Analysis of Observational Studies

BackgroundMany observational studies have shown that exposure to fluoride in drinking water is associated with hip fracture risk. However, the findings are varied or even contradictory. In this work, we performed a meta-analysis to assess the relationship between fluoride exposure and hip fracture risk.MethodsPubMed and EMBASE databases were searched to identify relevant observational studies from the time of inception until March 2014 without restrictions. Data from the included studies were extracted and analyzed by two authors. Summary relative risks (RRs) with corresponding 95% confidence intervals (CIs) were pooled using random- or fixed-effects models as appropriate. Sensitivity analyses and meta-regression were conducted to explore possible explanations for heterogeneity. Finally, publication bias was assessed.ResultsFourteen observational studies involving thirteen cohort studies and one case-control study were included in the meta-analysis. Exposure to fluoride in drinking water does not significantly increase the incidence of hip fracture (RRs, 1.05; 95% CIs, 0.96–1.15). Sensitivity analyses based on adjustment for covariates, effect measure, country, sex, sample size, quality of Newcastle–Ottawa Scale scores, and follow-up period validated the strength of the results. Meta-regression showed that country, gender, quality of Newcastle–Ottawa Scale scores, adjustment for covariates and sample size were not sources of heterogeneity. Little evidence of publication bias was observed.ConclusionThe present meta-analysis suggests that chronic fluoride exposure from drinking water does not significantly increase the risk of hip fracture. Given the potential confounding factors and exposure misclassification, further large-scale, high-quality studies are needed to evaluate the association between exposure to fluoride in drinking water and hip fracture risk.     

Maternal Benzene Exposure during Pregnancy and Risk of Childhood Acute Lymphoblastic Leukemia: A Meta-Analysis of Epidemiologic Studies

Background

The prevalence of childhood leukemia is increasing rapidly all over the world. However, studies on maternal benzene exposure during pregnancy and childhood acute lymphoblastic leukemia (ALL) have not been systematically assessed. Therefore, we performed a meta-analysis to investigate the association between maternal solvent, paint, petroleum exposure, and smoking during pregnancy and risk of childhood ALL.

Methods

Relevant studies up to September 1^st, 2013 were identified by searching the PubMed, EMBASE, Cochrane library and the Web of Science databases. The effects were pooled using either fixed or random effect models based on the heterogeneity of the studies.

Results

Twenty-eight case-control studies and one cohort study were included for analysis, with a total of 16,695 cases and 1,472,786 controls involved. Pooled odds ratio (OR) with 95% confidence interval (CI) for ALL was 1.25 (1.09, 1.45) for solvent, 1.23 (1.02, 1.47) for paint, 1.42 (1.10, 1.84) for petroleum exposure, and 0.99 (0.93, 1.06) for maternal smoking during pregnancy. No publication bias was found in this meta-analysis and consistent results were observed for subgroup and sensitivity analyses.

Conclusions

Childhood ALL was associated with maternal solvent, paint, and petroleum exposure during pregnancy. No association was found between ALL and maternal smoking during pregnancy. Avoidance of maternal occupational and environmental benzene exposure during pregnancy could contribute to a decrease in the risk of childhood ALL.     

Photodynamic therapy and tumor imaging of hypericin-treated squamous cell carcinoma

Background

The use of cellular and cordless telephones has increased dramatically during the last decade. There is concern of health problems such as malignant diseases due to microwave exposure during the use of these devices. The brain is the main target organ.

Methods

Since the second part of the 1990's we have performed six case-control studies on this topic encompassing use of both cellular and cordless phones as well as other exposures. Three of the studies concerned brain tumours, one salivary gland tumours, one non-Hodgkin lymphoma (NHL) and one testicular cancer. Exposure was assessed by self-administered questionnaires.

Results

Regarding acoustic neuroma analogue cellular phones yielded odds ratio (OR) = 2.9, 95 % confidence interval (CI) = 2.0–4.3, digital cellular phones OR = 1.5, 95 % CI = 1.1–2.1 and cordless phones OR = 1.5, 95 % CI = 1.04–2.0. The corresponding results were for astrocytoma grade III-IV OR = 1.7, 95 % CI = 1.3–2.3; OR = 1.5, 95 % CI = 1.2–1.9 and OR = 1.5, 95 % CI = 1.1–1.9, respectively. The ORs increased with latency period with highest estimates using > 10 years time period from first use of these phone types. Lower ORs were calculated for astrocytoma grade I-II. No association was found with salivary gland tumours, NHL or testicular cancer although an association with NHL of T-cell type could not be ruled out.

Conclusion

We found for all studied phone types an increased risk for brain tumours, mainly acoustic neuroma and malignant brain tumours. OR increased with latency period, especially for astrocytoma grade III-IV. No consistent pattern of an increased risk was found for salivary gland tumours, NHL, or testicular cancer.     

Common genetic variants (rs4779584 and rs10318) at 15q13.3 contributes to colorectal adenoma and colorectal cancer susceptibility: evidence based on 22 studies

Several genome-wide association studies on colorectal cancer (CRC) have reported similar findings of a new susceptibility locus, 15q13.3. After that, a number of studies have reported that the rs4779584 and rs10318 polymorphisms at chromosome 15q13.3 have been implicated in CRC and colorectal adenoma (CRA) risk; however, these studies have yielded inconsistent results. To investigate this inconsistency, we performed a meta-analysis of 22 studies involving a total of 48,468 CRC cases, 4,189 CRA cases, and 85,105 controls for the two polymorphisms to evaluate its effect on genetic susceptibility for CRC/CRA. Potential sources of heterogeneity and publication bias were also systematically explored. Overall, the summary odds ratio (OR) of rs4779584-T variant for CRC was 1.13 (95 % CI 1.09–1.16, P < 10^?5) and 1.15 (95 % CI 1.04–1.28, P = 0.006) for CRA. After stratified by ethnicity, significantly increased CRC risks were found for rs4779584 polymorphism among East Asians and Caucasians, while no significant associations were detected among African American and other ethnic populations. A meta-analysis of studies on the rs10318 polymorphism also showed significant overall association with CRC, yielding a per-allele OR of 1.13 (95 % CI 1.02–1.24, P = 0.02). In the subgroup analysis by ethnicity, significantly increased CRC risks were found in Caucasians; whereas no significant associations were found among East Asians and African Americans. This meta-analysis demonstrated that the rs4779584 and rs10318 polymorphism at 15q13.3 is a risk factor associated with increased CRC/CRA susceptibility, but these associations vary in different ethnic populations.     

Persistent infection by HCV and EBV in peripheral blood mononuclear cells and risk of non-Hodgkin's lymphoma

Hepatitis C virus (HCV) and Epstein–Barr virus (EBV) have been repeatedly associated with risk of non-Hodgkin's lymphoma (NHL) in studies focusing on serological evidence of infection. We investigated NHL risk in association with detection of HCV-RNA or EBV-DNA in the peripheral blood mononuclear cells (PBMC). The study involved 91 NHL cases and 182 controls nested in the Italian branch of the EPIC (European Prospective Investigation of Cancer and nutrition) cohort, which obtained blood samples from 47,749 healthy volunteers between 1993 and 1998 in 5 Italian cities. NHL cases were identified until June 2005 through linkage with records of the Cancer, Mortality, and Hospital Discharge Registries. For all study subjects, we performed viral genome analyses on DNA and RNA extracted from buffy-coats and analysed EBV and HCV antibodies. The odds ratios (ORs) of NHL were 1.2 (95% confidence intervals: 0.4–3.8; 5 exposed cases) for PBMC HCV infection and 1.2 (0.7–2.3; 24 exposed cases) for PBMC EBV infection. Similar OR estimates were found for detection of EBV and HCV antibodies. These null results, although based on a relatively small sample size, suggest that persistent EBV and HCV infection in the PBMC is not a stronger predictor of NHL risk than serological evidence of infection.     

miR-499 rs3746444 polymorphism is associated with cancer development among Asians and related to breast cancer susceptibility

To derive a more precise estimation of the relationship between miR-499 rs3746444 polymorphism (A>G) and cancer risk, a meta-analysis was performed. A total of 9 studies including 6,077 cases and 7,199 controls were involved in this meta-analysis. Overall, no significantly elevated cancer risk was associated with miR-499 G allele when all studies were pooled into the meta-analysis (AG vs. AA: OR?=?1.14, 95?% CI?=?0.98–1.32; GG vs. AA: OR?=?1.12, 95?% CI?=?0.95–1.33; dominant model: OR?=?1.13, 95?% CI?=?0.99–1.29; recessive model: OR?=?1.05, 95?% CI?=?0.83–1.33). In the subgroup analysis by ethnicity, significantly increased risk was only found for Asians (dominant model: OR?=?1.22, 95?% CI?=?1.02–1.46). When stratified by study design, no statistically significantly elevated risks were found in hospital-based studies or population-based studies. In the subgroup analysis by cancer type, significant cancer risk change was only found for breast cancer when miR-499 G allele was included (dominant model: OR?=?1.13, 95?% CI?=?1.01–1.26). In conclusion, this meta-analysis suggests that the miR-499 rs3746444 polymorphism (A>G) is a low-penetrant risk factor for cancer development among Asians and may contribute to breast cancer susceptibility.     

Potential Importance of Inhalation Exposures for Wildlife Using Screening-Level Ecological Risk Assessment

Ecological risk assessments (ERAs) have largely ignored exposure to wildlife via inhalation on the assumption that it is negligible compared to the ingestion route of exposure. The assessment of inhalation risk also has been limited due to a paucity of relevant ecotoxicity data. This article presents toxicity reference values (TRVs) for small mammals based on chronic or subchronic exposure studies for a range of organic and trace metal contaminants and ecologically relevant inhalation endpoints. Potential risk to small mammals due to ingestion and inhalation exposure were compared in two hypothetical air emission scenarios for a point source (incinerator) and non-point source emissions (vehicular emissions). Using two screening-level ERAs, we conclude that it may now be time to reconsider inhalation risk to wildlife in the case of atmospheric emissions of some metals and volatile organic compounds (VOCs). In the case of birds, the toxicological database remains too small to assess risks via this pathway. However, for mammals, we suggest that inhalation exposures to contaminants such as cadmium, benzene, and other VOCs could be important.     

Effects of environmental benzene: micronucleus frequencies and haematological values in traffic police working in an urban area

Among the toxic chemicals present in the ambient air of urban centres, benzene raises particular concern due to its haematoxicity and leukaemogenic hazards, probably related to clastogenic factors. However, little is known about the health risks associated with environmental--rather than industrial--exposure to benzene. We analysed micronucleus (MN) frequencies in peripheral lymphocytes by use of the cytokinesis-block technique, and haematological parameters among 49 traffic police and 36 indoor workers (controls) in the city of Bologna. The analysis of urban air provided by a municipal air-quality monitoring station indicated that the levels of environmental benzene were often above the recommended threshold level (10 microg/m3) whereas other pollutants--nitrogen oxides, polycyclic aromatic hydrocarbon compounds, total suspended particulate matter, carbon monoxide, sulfur dioxide--did not exceed the maximum atmospheric concentration established for air-quality standards. Mean levels of individual airborne benzene exposure--as measured by personal devices worn during 4-h morning work-shifts--were six-fold higher in the traffic police than in controls (P=0.001). While no significant difference in haematological parameters was found between the two groups, MN frequency was significantly higher among the traffic police than in indoor workers (P=0.001). Among the study population, MN frequency was found to increase with age, but no influence was observed for gender or smoking. Although it cannot be excluded that the increase of MN frequency observed in traffic police could also depend, apart from benzene, on the complex mixture of pollutants encountered in urban air, our data indicate that elevated personal benzene exposure could represent a genetic risk. The analysis of biomarkers of genetic damage in subjects particularly exposed to environmental benzene deserves careful study.     

Lack of association between miR-149 C>T polymorphism and cancer susceptibility: a meta-analysis based on 4,677 cases and 4,830 controls

To derive a more precise estimation of the relationship between miR-149 C>T polymorphism and cancer risk, a meta-analysis was performed. A total of 8 studies including 4,677 cases and 4,830 controls were involved in this meta-analysis. Overall, no significantly elevated cancer risk was associated with miR-149 T allele when all studies were pooled into the meta-analysis (CT vs. CC: OR = 0.977, 95 % CI = 0.882-1.082; TT vs. CC: OR = 0.985, 95 % CI = 0.857-1.132; dominant model: OR = 0.984, 95 % CI = 0.893-1.084; recessive model: OR = 1.026, 95 % CI = 0.931-1.132). In the subgroup analysis by ethnicity or study design, no significantly increased risks were found under all models. When stratified by cancer type, there were no significant cancer risk changes for lung cancer, breast cancer or colorectal cancer when miR-149 T allele was included. In conclusion, this meta-analysis suggests that the miR-149 C>T polymorphism may not contribute to cancer susceptibility.     

Mortality from solid cancers other than lung,liver, and bone in relation to external dose among plutonium and non-plutonium workers in the Mayak Worker Cohort

Exposure to ionizing radiation has well-documented long-term effects on cancer rates and other health outcomes in humans. While in vitro experimental studies had demonstrated that the nature of some radiation effects depend on both total dose of the radiation and the dose rate (i.e., the pattern of dose distribution over time), the question of whether or not the carcinogenic effect of radiation exposure depends on the dose rate remains unanswered. Another issue of interest concerns whether or not concomitant exposure to external gamma rays and inhaled plutonium aerosols has any effect on the external exposure effects. The analyses of the present paper focus on the risk of solid cancers at sites other than lung, liver, and bone in Mayak workers. Recent findings are reviewed indicating that there is no evidence of plutonium dose response for these cancers in the Mayak worker cohort. Then the evidence for differences in the external dose effects among workers with and without the potential for exposure to alpha particles from inhaled plutonium is examined. It is found that there is no evidence that exposure to plutonium aerosols significantly affects the risk associated with external exposure. While the Mayak external dose risk estimate of an excess relative risk of 0.16 per Gy is somewhat lower than an appropriately normalized risk estimate from the Life Span Study of Japanese atomic bomb survivors, the uncertainties in these estimates preclude concluding that the external dose excess relative risks of this group of solid cancers differ in the two cohorts.     

Exposure to Second-Hand Smoke and the Risk of Tuberculosis in Children and Adults: A Systematic Review and Meta-Analysis of 18 Observational Studies

Background

According to WHO Global Health Estimates, tuberculosis (TB) is among the top ten causes of global mortality and ranks second after cardiovascular disease in most high-burden regions. In this systematic review and meta-analysis, we investigated the role of second-hand smoke (SHS) exposure as a risk factor for TB among children and adults.

Methods and Findings

We performed a systematic literature search of PubMed, Embase, Scopus, Web of Science, and Google Scholar up to August 31, 2014. Our a priori inclusion criteria encompassed only original studies where latent TB infection (LTBI) and active TB disease were diagnosed microbiologically, clinically, histologically, or radiologically. Effect estimates were pooled using fixed- and random-effects models. We identified 18 eligible studies, with 30,757 children and 44,432 adult non-smokers, containing SHS exposure and TB outcome data for inclusion in the meta-analysis. Twelve studies assessed children and eight studies assessed adult non-smokers; two studies assessed both populations. Summary relative risk (RR) of LTBI associated with SHS exposure in children was similar to the overall effect size, with high heterogeneity (pooled RR 1.64, 95% CI 1.00–2.83). Children showed a more than 3-fold increased risk of SHS-associated active TB (pooled RR 3.41, 95% CI 1.81–6.45), which was higher than the risk in adults exposed to SHS (summary RR 1.32, 95% CI 1.04–1.68). Positive and significant exposure–response relationships were observed among children under 5 y (RR 5.88, 95% CI 2.09–16.54), children exposed to SHS through any parent (RR 4.20, 95% CI 1.92–9.20), and children living under the most crowded household conditions (RR 5.53, 95% CI 2.36–12.98). Associations for LTBI and active TB disease remained significant after adjustment for age, biomass fuel (BMF) use, and presence of a TB patient in the household, although the meta-analysis was limited to a subset of studies that adjusted for these variables. There was a loss of association with increased risk of LTBI (but not active TB) after adjustment for socioeconomic status (SES) and study quality. The major limitation of this analysis is the high heterogeneity in outcomes among studies of pediatric cases of LTBI and TB disease.

Conclusions

We found that SHS exposure is associated with an increase in the relative risk of LTBI and active TB after controlling for age, BMF use, and contact with a TB patient, and there was no significant association of SHS exposure with LTBI after adjustment for SES and study quality. Given the high heterogeneity among the primary studies, our analysis may not show sufficient evidence to confirm an association. In addition, considering that the TB burden is highest in countries with increasing SHS exposure, it is important to confirm these results with higher quality studies. Research in this area may have important implications for TB and tobacco control programs, especially for children in settings with high SHS exposure and TB burden.     

Safety of Hormonal Replacement Therapy and Oral Contraceptives in Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis

Background

There is conflicting data regarding exogenous sex hormones [oral contraceptives (OC) and hormonal replacement therapy (HRT)] exposure and different outcomes on Systemic Lupus Erythematosus (SLE). The aim of this work is to determine, through a systematic review and meta-analysis the risks associated with estrogen use for women with SLE as well as the association of estrogen with developing SLE.

Methods and Findings

MEDLINE, EMBASE, SciElo, BIREME and the Cochrane library (1982 to July 2012), were databases from which were selected and reviewed (PRISMA guidelines) randomized controlled trials, cross-sectional, case-control and prospective or retrospective nonrandomized, comparative studies without language restrictions. Those were evaluated by two investigators who extracted information on study characteristics, outcomes of interest, risk of bias and summarized strength of evidence. A total of 6,879 articles were identified; 20 full-text articles were included. Thirty-two meta-analyses were developed. A significant association between HRT exposure (Random model) and an increased risk of developing SLE was found (Rate Ratio: 1.96; 95%-CI: 1.51–2.56; P-value<0.001). One of eleven meta-analyses evaluating the risk for SLE associated with OC exposure had a marginally significant result. There were no associations between HRT or OC exposure and specific outcomes of SLE. It was not always possible to Meta-analyze all the available data. There was a wide heterogeneity of SLE outcome measurements and estrogen therapy administration.

Conclusion

An association between HRT exposure and SLE causality was observed. No association was found when analyzing the risk for SLE among OC users, however since women with high disease activity/Thromboses or antiphospholipid-antibodies were excluded from most of the studies, caution should be exercised in interpreting the present results. To identify risk factors that predispose healthy individuals to the development of SLE who are planning to start HRT or OC is suggested.     

Space-Time Clustering of Non-Hodgkin Lymphoma Using Residential Histories in a Danish Case-Control Study

Non-Hodgkin lymphoma (NHL) is a frequent cancer and incidence rates have increased markedly during the second half of the 20^th century; however, the few established risk factors cannot explain this rise and still little is known about the aetiology of NHL. Spatial analyses have been applied in an attempt to identify environmental risk factors, but most studies do not take human mobility into account. The aim of this study was to identify clustering of NHL in space and time in Denmark, using 33 years of residential addresses. We utilised the nation-wide Danish registers and unique personal identification number that all Danish citizens have to conduct a register-based case-control study of 3210 NHL cases and two independent control groups of 3210 each. Cases were identified in the Danish Cancer Registry and controls were matched by age and sex and randomly selected from the Civil Registration System. Residential addresses of cases and controls from 1971 to 2003 were collected from the Civil Registration System and geocoded. Data on pervious hospital diagnoses and operations were obtained from the National Patient Register. We applied the methods of the newly developed Q-statistics to identify space-time clustering of NHL. All analyses were conducted with each of the two control groups, and we adjusted for previous history of autoimmune disease, HIV/AIDS or organ transplantation. Some areas with statistically significant clustering were identified; however, results were not consistent across the two control groups; thus we interpret the results as chance findings. We found no evidence for clustering of NHL in space and time using 33 years of residential histories, suggesting that if the rise in incidence of NHL is a result of risk factors that vary across space and time, the spatio-temporal variation of such factors in Denmark is too small to be detected with the applied method.     

Statin Use and Risk of Lung Cancer: a Meta-Analysis of Observational Studies and Randomized Controlled Trials

Clinical studies have shown that statin use may alter the risk of lung cancer. However, these studies yielded different results. To quantify the association between statin use and risk of lung cancer, we performed a detailed meta-analysis. A literature search was carried out using MEDLINE, EMBASE and COCHRANE database between January 1966 and November 2012. Before meta-analysis, between-study heterogeneity and publication bias were assessed using adequate statistical tests. Fixed-effect and random-effect models were used to calculate the pooled relative risks (RR) and corresponding 95% confidence intervals (CIs). Subgroup analyses, sensitivity analysis and cumulative meta-analysis were also performed. A total of 20 (five randomized controlled trials, eight cohorts, and seven case–control) studies contributed to the analysis. Pooled results indicated a non-significant decrease of total lung cancer risk among all statin users (RR = 0.89, 95% CI [0.78, 1.02]). Further, long-term statin use did not significantly decrease the risk of total lung cancer (RR = 0.80, 95% CI [0.39 , 1.64]). In our subgroup analyses, the results were not substantially affected by study design, participant ethnicity, or confounder adjustment. Furthermore, sensitivity analysis confirmed the stability of results. The findings of this meta-analysis suggested that there was no significant association between statin use and risk of lung cancer. More studies, especially randomized controlled trials and high quality cohort studies are warranted to confirm this association.     

Multiple myeloma and occupation: A pooled analysis by the International Multiple Myeloma Consortium

Objective: We investigated occupational risk of multiple myeloma (MM) in a pooled analysis of five international case–control studies. Methods: We calculated the odds ratio and its 95% confidence interval for selected occupations with unconditional regression analysis in 1959 MM cases and 6192 controls, by pooling study-specific risks using random-effects meta-analysis. Exposure to organic solvents was assessed with a job-exposure matrix (JEM). Results: Gardeners and nursery workers combined, most likely exposed to pesticides, showed a 50% increase in risk (OR = 1.50, 95% CI 0.9–2.3), while other farming jobs did not. Metal processors (OR = 1.55, 95% CI 0.9–2.3), female cleaners (OR = 1.32, 95% CI 1.0–1.8), and high level exposure to organic solvents (OR = 1.38, 95% CI 0.96–1.8) also showed moderately increased risks. Conclusions: Additional case–control studies of MM aetiology are warranted to further investigate the nature of the repeatedly reported increase in MM risk in several occupational groups.     

Variation in effects of non-Hodgkin lymphoma risk factors according to the human leukocyte antigen (HLA)-DRB1*01:01 allele and ancestral haplotype 8.1

Genetic variations in human leukocyte antigens (HLA) are critical in host responses to infections, transplantation, and immunological diseases. We previously identified associations with non-Hodgkin lymphoma (NHL) and the HLA-DRB1*01:01 allele and extended ancestral haplotype (AH) 8.1 (HLA-A*01-B*08-DR*03-TNF-308A). To illuminate how HLA alleles and haplotypes may influence NHL etiology, we examined potential interactions between HLA-DRB1*01:01 and AH 8.1, and a wide range of NHL risk factors among 685 NHL cases and 646 controls from a United States population-based case-control study. We calculated odds ratios and 95% confidence intervals by HLA allele or haplotype status, adjusted for sex, age, race and study center for NHL and two major subtypes using polychotomous unconditional logistic regression models. The previously reported elevation in NHL risk associated with exposures to termite treatment and polychlorinated biphenyls were restricted to individuals who did not possess HLA-DRB1*01:01. Previous associations for NHL and DLBCL with decreased sun exposure, higher BMI, and autoimmune conditions were statistically significant only among those with AH 8.1, and null among those without AH 8.1. Our results suggest that NHL risk factors vary in their association based on HLA-DRB1*01:01 and AH 8.1 status. Our results further suggest that certain NHL risk factors may act through a common mechanism to alter NHL risk. Finally, control participants with either HLA-DRB1*01:01 or AH 8.1 reported having a family history of NHL twice as likely as those who did not have either allele or haplotype, providing the first empirical evidence that HLA associations may explain some of the well-established relationship between family history and NHL risk.     

Toxoplasma gondii infection/exposure and the risk of brain tumors: A systematic review and meta-analysis

BackgroundBrain tumors are among the most fatal cancers with substantial morbidity and mortality worldwide. Epidemiologic evidence suggests that infectious agents, especially, protozoan parasite Toxoplasma gondii could be a possible risk factor or contributor. Here, we performed a systematic review and meta-analysis to evaluate the possible association between T. gondii infection/exposure and risk of brain tumors.MethodsWe searched the PubMed, Embase, Scopus, and Web of Science collection databases from inception through 1st of December 2021. Pooled estimates of odds ratios (ORs) and 95% confidence intervals (CIs) were generated using random effects models. We did the subgroup analysis according to tumor types. Statistical tests for heterogeneity and sensitivity analyses were applied.ResultsA total of seven eligible studies comprising 2323 patients diagnosed with brain tumors and 5131 healthy controls were included in the meta-analysis. T. gondii infection/exposure prevalence was 24.2% (95%CI, 12.7%–41.2) in cases and 12.9% (95%CI, 7.0–22.6%) in control subjects. Pooled analysis showed an overall OR of 1.96 (95%CI, 1.37–2.80), indicating a significant increased risk of brain tumors associated with T. gondii infection/exposure. In subgroup analysis T. gondii infection/exposure was significantly associated with gliomas (OR: 1.64, 95%CI, 1.15–2.33), meningioma (OR: 2.30, 95%CI, 1.0–5.27) and other types of brain tumors (OR: 2.19, 95%CI, 1.02–4.71).ConclusionThis study provides suggestive evidence for an association between T. gondii infection/exposure and brain tumors. Our findings should be further confirmed by well-designed cohort studies with strict control of confounders. Moreover, we suggest that future studies also focus on the effect of T. gondii infection/exposure to the types of brain tumors.     

Setting Risk-Based Occupational Exposure Limits for No-Threshold Carcinogens

Several regulators have recently issued so-called risk-based occupational exposure limits for carcinogenic substances, and also reported estimates of the risk of fatality that exposure to the limit value would give rise to. This practice provides an opportunity to study how differences in the exposure limits set by different regulators are influenced by differences in the scientific judgment (what is the risk at different levels?) and in the policy judgment (how should large risks be accepted?). Based on a broad search, a list was compiled of exposure limits for carcinogens that the respective regulator associates with a numerical risk estimate. For benzene, such data was available from six regulators. The differences in estimates of the risk/exposure relationship and in risk tolerance were about equal in size for benzene, while the range for acceptability was somewhat wider. A similar pattern was observed, although less clearly, for substances with data from only two or three regulators. It is concluded that the science factor and the policy factor both contribute to differences in exposure limits for carcinogens. It was not possible to judge which of these two factors has the larger influence.     

A Meta-Analysis of Parental Smoking and the Risk of Childhood Brain Tumors

Objective

Previous studies regarding the association between parental smoking and the risk of childhood brain tumors (CBT) have reported inconsistent results. We performed a meta-analysis to summarize evidence on this association and to quantify the potential dose-response relationship.

Methods

A systematic literature search was conducted in the Medline and Embase databases. The summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated. Dose–response meta-analysis was also performed for studies that reported categorical risk estimates for a series of smoking exposure levels.

Results

A total of 17 studies fulfilled the inclusion criteria. In the meta-analyses, the summary RRs (95% CIs) of CBT for maternal smoking during pregnancy, paternal smoking during pregnancy, maternal smoking before pregnancy, and paternal smoking before pregnancy were 0.96 (0.86–1.07), 1.09 (0.97–1.22), 0.93 (0.85–1.00), and 1.09 (1.00–1.20), respectively. Dose-response meta-analysis also showed no significant association between parental smoking and the risk of CBT.

Conclusions

Findings from our meta-analysis indicate that parental smoking may not be associated with a risk of CBT.