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.     

CXCR5 polymorphisms in non-Hodgkin lymphoma risk and prognosis

CXCR5 [chemokine (C-X-C motif) receptor 5; also known as Burkitt lymphoma receptor 1 (BCR1)] is expressed on mature B-cells, subsets of CD4⁺ and CD8⁺ T-cells, and skin-derived migratory dendritic cells. Together with its ligand, CXCL13, CXCR5 is involved in guiding B-cells into the B-cell zones of secondary lymphoid organs as well as T-cell migration. This study evaluated the role of common germline genetic variation in CXCR5 in the risk and prognosis of non-Hodgkin lymphoma (NHL) using a clinic-based study of 1,521 controls and 2,694 NHL cases including 710 chronic lymphocytic leukemia/small lymphocytic lymphoma, 586 diffuse large B-cell lymphoma (DLBCL), 588 follicular lymphoma (FL), 137 mantle cell lymphoma (MCL), 230 marginal zone lymphoma (MZL), and 158 peripheral T-cell lymphoma (PTCL). Of the ten CXCR5 tag SNPs in our study, five were associated with risk of NHL, with rs1790192 having the strongest association (OR 1.19, 95 % CI 1.08–1.30; p = 0.0003). This SNP was most strongly associated with the risk of FL (OR 1.44, 95 % CI 1.25–1.66; p = 3.1 × 10^?7), with a lower degree of association with DLBCL (OR 1.16, 95 % CI 1.01–1.33; p = 0.04) and PTCL (OR 1.29, 95 % CI 1.02–1.64; p = 0.04) but no association with the risk of MCL or MZL. For FL patients that were observed as initial disease management, the number of minor alleles of rs1790192 was associated with better event-free survival (HR 0.64; 95 % CI 0.47–0.87; p = 0.004). These results provide additional evidence for a role of host genetic variation in CXCR5 in lymphomagenesis, particularly for FL.     

A systematic review and meta-analysis of immune checkpoint therapy in relapsed or refractory non-Hodgkin lymphoma; a friend or foe?

Over the last decades, a revolution has occurred in oncology with the development of immune checkpoint inhibitors (ICIs). Following tremendous successes in solid tumors, interest has risen to explore these inhibitors in hematologic malignancies; while Hodgkin's lymphoma (HL) has shown overwhelming achievements, available data on different types of non-Hodgkin's lymphoma (NHL) vary considerably. To the best of our knowledge, no meta-analysis has assessed the efficacy and safety of ICI therapy in relapsed or refractory NHL patients. Meta-analysis of the included studies (n = 29) indicated PD-1 may probably be the more attractive ICI target rather than PD-L1 and CTLA-4 in NHL patients. Also, there is a plausible correlation between NHL subtypes and response to ICI therapy. While MF, ENKTL, RT, and PMBCL showed promising responses to ICI monotherapy, neither FL nor DLBCL had satisfactory responses; further necessitating novel strategies such as the application of ICIs in combination with other treatment strategies. Notably, among different combinations, BTK inhibitors showed an obvious improvement as compared to ICI monotherapy in both FL and DLBCL, however, the best results were obtained when ICI was combined with anti-CD20 monoclonal antibodies. Finally, while most NHL patients who received ICI treatment have experienced mild AEs, larger trials with long-term follow-up are required to confirm the safety, as well as the efficacy, of ICI therapy in NHL patients.     

Cyclin D1 splice variant and risk for non-Hodgkin lymphoma

To investigate the role of cell cycle gene variations in lymphomagenesis, we evaluated associations (odds ratios [OR] and 95% confidence intervals [CI]) in polymorphisms from seven candidate genes in 1,172 non-Hodgkin lymphoma (NHL) cases and 982 population-based controls. The cyclin D1 (CCND1) splice variant G870A (rs603965) increased NHL risk (OR_AA = 1.4, 95% CI = 1.1–1.8, P-trend = 0.021), which was consistent for four B-cell subtypes. As CCND1 expression indicates poor NHL prognosis, our results, if true, would support its potentially dual importance in NHL etiology and survival.Electronic Supplementary Material Supplementary material is available to authorised users in the online version of this article at .     

Genetic variation in cell death genes and risk of non-Hodgkin lymphoma

Background

Non-Hodgkin lymphomas are a heterogeneous group of solid tumours that constitute the 5^th highest cause of cancer mortality in the United States and Canada. Poor control of cell death in lymphocytes can lead to autoimmune disease or cancer, making genes involved in programmed cell death of lymphocytes logical candidate genes for lymphoma susceptibility.

Materials and Methods

We tested for genetic association with NHL and NHL subtypes, of SNPs in lymphocyte cell death genes using an established population-based study. 17 candidate genes were chosen based on biological function, with 123 SNPs tested. These included tagSNPs from HapMap and novel SNPs discovered by re-sequencing 47 cases in genes for which SNP representation was judged to be low. The main analysis, which estimated odds ratios by fitting data to an additive logistic regression model, used European ancestry samples that passed quality control measures (569 cases and 547 controls). A two-tiered approach for multiple testing correction was used: correction for number of tests within each gene by permutation-based methodology, followed by correction for the number of genes tested using the false discovery rate.

Results

Variant rs928883, near miR-155, showed an association (OR per A-allele: 2.80 [95% CI: 1.63–4.82]; p_F = 0.027) with marginal zone lymphoma that is significant after correction for multiple testing.

Conclusions

This is the first reported association between a germline polymorphism at a miRNA locus and lymphoma.     

One-carbon metabolism gene polymorphisms and risk of non-Hodgkin lymphoma in Australia

Dysregulation of the one-carbon metabolic pathway, which controls nucleotide synthesis and DNA methylation, may promote lymphomagenesis. We evaluated the association between polymorphisms in one-carbon metabolism genes and risk of non-Hodgkin lymphoma (NHL) in a population-based case-control study in Australia. Cases (n = 561) and controls (n = 506) were genotyped for 14 selected single-nucleotide polymorphisms in 10 genes (CBS, FPGS, FTHFD, MTHFR, MTHFS, MTR, SHMT1, SLC19A1, TCN1, and TYMS). We also conducted a meta-analysis of all studies of Caucasian populations investigating the association between MTHFR Ex5+79C > T (a.k.a., 677C>T) and NHL risk. A global test of 13 genotypes was statistically significant for diffuse large B-cell lymphoma (DLBCL; P = 0.008), but not for follicular lymphoma (FL; P = 0.27) or all NHL (P = 0.17). The T allele at MTHFR Ex5+79 was marginally significantly associated with all NHL (OR = 1.25, 95% CI = 0.98–1.59) and DLBCL (1.36, 0.96–1.93). The T allele at TYMS Ex8+157 was associated with a reduced risk of FL (0.64, 0.46–0.91). An elevated risk of NHL was also observed among carriers of the G allele at FTHFD Ex21+31 (all NHL, 1.31, 1.02–1.69; DLBCL, 1.50, 1.05–2.14). A meta-analysis of 11 studies conducted in Caucasian populations of European origin (4,121 cases and 5,358 controls) supported an association between the MTHFR Ex5+79 T allele and increased NHL risk (additive model, P = 0.01). In conclusion, the results of this study suggest that genetic polymorphisms of one-carbon metabolism genes such as MTHFR and TYMS may influence susceptibility to NHL. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Circulating visfatin levels and cancers risk: A systematic review and meta-analysis

Visfatin levels have been reported to be abnormal in many types of cancers. However, epidemiological studies yielded inconsistent results. Therefore, a meta-analysis was performed to assess the association between circulating visfatin levels and cancer risk. A systematic search was conducted for relevant studies in health-related electronic databases up to March 2018. Data related to standard mean difference (SMD) and overall odds ratio (ORS) were collected and analyzed. Summary SMD and pooled OR with 95% CIs were calculated using a random-effect model. Funnel plot and Egger's linear regression test were conducted to examine the risk of publication bias. A total of 27 studies with 2,693 cases and 3,040 healthy controls were included in meta-analysis for pooling SMD analysis. The results of the meta-analysis showed a significant higher visfatin levels in patients with various cancers than in controls, with a pooled SMD of 0.88, 95% CI = 0.56–1.20, p = 0.000. In subgroup, metaregression, Galbraith plot, and sensitivity analysis showed no substantial difference among all the analyzed factors. Data from 14 studies were also used for pooling ORs analysis. Metaresults revealed that high visfatin levels were associated with cancer risk (OR = 1.24, 95% CI: 1.14–1.34, p = 0.000). No evidence of publication bias was observed for pooling ORs and SMD analysis. This meta-analysis indicated a significant association between high circulating visfatin levels and increased risk of various cancers. Visfatin may represent a potential biomarker for early detection of cancers who may benefit from preventive treatment.Note.     

Sexually transmitted infections and prostate cancer risk: A systematic review and meta-analysis

Prostate cancer (PC) is the second most incident cancer and the sixth cause of death by cancer in men worldwide. Despite extensive research efforts, no modifiable risk factors have been consistently identified for PC risk. A number of studies have focused on possible relationships between sexually transmitted infections (STIs) and PC. We performed a meta-analysis to explore the association between infection caused by Neisseria gonorrheae, Treponema pallidum, Chlamydia trachomatis, Trichomonas vaginalis, Ureaplasma urealyticum, Mycoplasma hominis, Herpes Simplex Virus types 1 and 2, Human Herpes Virus 8 and Cytomegalovirus, and PC. We conducted a comprehensive, systematic bibliographic search of medical literature to identify relevant studies. We calculated summary relative risk (SRR) and 95% confidence intervals (CI) for the association between each STI and PC through random effect models. Subgroup, meta-regression and sensitivity analyses were carried out to detect between-study heterogeneity and bias. We included 47 studies published between 1971 and 2011. Men who reported having ever had any STI in lifetime had an increased PC (SRR 1.49, 95% CI 1.19–1.92). We found a significantly increased PC risk in men having had gonorrhoea (SRR 1.20, 95% CI 1.05–1.37). No other single STI was significantly associated with PC. Due to high incidence of both STIs and PC worldwide, prevention of STIs may help preventing a considerable number of PC cases.     

原发肾上腺淋巴瘤1例并文献复习

目的:探讨原发肾上腺淋巴瘤(PAL)的临床特点,提高对该病的认识.方法:对1例原发肾上腺淋巴瘤患者的资料进行分析,并结合国内外相关文献进行总结.结果:原发肾上腺淋巴瘤好发于老年男性,可表现为局部症状如腹痛,腰痛,也可表现为乏力,发热,体重减低等全身症状,50%病人可出现肾上腺功能不全的症状.一些病人是在行影像学检查时因偶然发现肾上腺的肿物,经病理检查而确诊的.该病多累及双侧肾上腺,最常见的病理类型是弥漫大B细胞型.原发肾上腺淋巴瘤的治疗包括手术、化疗、放疗以及它们的不同组合.该病恶性程度高,进展迅速,预后差.结论:原发肾上腺淋巴瘤虽然少见,但在肾上腺肿瘤,尤其是快速增长的肾上腺肿瘤的鉴别诊断中应考虑到它的可能,及时进行病理检查可尽早确诊.     

CNS lymphoma masquerading as stroke: Cases report and literature review

Central nervous system (CNS) involvement in Hodgkins lymphoma (HL) is extremely rare. There are only two reported case series of intracranial involvement of HL. CNS HL can be presented at any point in the course of HL, most mimicking with a prominent neurological symptom. This challenges the diagnosis of CNS involvement and stroke. Here, we report four cases of patients having refractory HL with CNS involvement to garner attention among neurologists for this rare disease presents with stroke symptoms and reviews its disease characteristics, prognosis, and treatment.     

Genetic predisposition and environmental risk factors to pancreatic cancer: A review of the literature

Some cases of pancreatic cancer (PC) are described to cluster within families. With the exception of PALLD gene mutations, which explain only a very modest fraction of familial cases, the genetic basis of familial PC is still obscure. Here the literature was reviewed in order to list the known genes, environmental factors, and health conditions associated with PC or involved in the carcinogenesis of the pancreas. Most of the genes listed are responsible for various well-defined cancer syndromes, such as CDKN2A (familial atypical mole-multiple melanoma, FAMMM), the mismatch repair genes (Lynch Syndrome), TP53 (Li-Fraumeni syndrome), APC (familial adenomatous polyposis), and BRCA2 (breast–ovarian familial cancer), where PC is part of the cancer spectrum of the disease. In addition, in this review I ranked known/possible risk factors extending the analysis to the hereditary pancreatitis (HP), diabetes, or to specific environmental exposures such as smoking. It appears that these factors contribute strongly to only a small proportion of PC cases. Recent work has revealed new genes somatically mutated in PC, including alterations within the pathways of Wnt/Notch and DNA mismatch repair. These new insights will help to reveal new candidate genes for the susceptibility to this disease and to better ascertain the actual contribution of the familial forms.     

Polymorphisms in DNA repair genes and risk of non-Hodgkin lymphoma among women in Connecticut

Several hereditary syndromes characterized by defective DNA repair are associated with high risk of non-Hodgkin lymphoma (NHL). To explore whether common polymorphisms in DNA repair genes affect risk of NHL in the general population, we evaluated the association between single nucleotide polymorphisms (SNPs) in DNA repair genes and risk of NHL in a population-based case–control study among women in Connecticut. A total of 518 NHL cases and 597 controls recruited into the study provided a biologic sample. Thirty-two SNPs in 18 genes involved in several DNA repair pathways were genotyped. Genotype data were analyzed by unconditional logistic regression adjusting for age and race. SNPs in four genes (ERCC5, ERCC2, WRN, and BRCA1) were associated with altered risk of NHL and diffuse large B-cell lymphoma (DLBCL), the major B cell subtype. In particular, ERCC5 Asp1104His was associated with increased risk of NHL overall (OR: 1.46; 95% CI: 1.13–1.88; P = 0.004), DLBCL (OR: 1.44; 95% CI: 0.99–2.09; P = 0.058), and also T cell lymphoma. WRN Cys1367Arg was associated with decreased risk of NHL overall (OR: 0.71; 95% CI: 0.56–0.91; P = 0.007) and DLBCL (OR: 0.66; 95% CI: 0.45–0.95; P = 0.024), as well as follicular and marginal zone lymphomas. Genetic polymorphisms in DNA repair genes, particularly ERCC5 and WRN, may play a role in the pathogenesis of NHL, especially for DLBCL. Further work is needed to extend these findings by carrying out extended haplotype analyses of these and related genes and to replicate the observations in other studies.     

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.     

Fear in animals: a meta-analysis and review of risk assessment

The amount of risk animals perceive in a given circumstance (i.e. their degree of 'fear') is a difficult motivational state to study. While many studies have used flight initiation distance as a proxy for fearfulness and examined the factors influencing the decision to flee, there is no general understanding of the relative importance of these factors. By identifying factors with large effect sizes, we can determine whether anti-predator strategies reduce fear, and we gain a unique perspective on the coevolution of predator and anti-predator behaviour. Based on an extensive review and formal meta-analysis, we found that predator traits that were associated with greater risk (speed, size, directness of approach), increased prey distance to refuge and experience with predators consistently amplified the perception of risk (in terms of flight initiation distance). While fish tolerated closer approach when in larger schools, other taxa had greater flight initiation distances when in larger groups. The presence of armoured and cryptic morphologies decreased perception of risk, but body temperature in lizards had no robust effect on flight initiation distance. We find that selection generally acts on prey to be sensitive to predator behaviour, as well as on prey to modify their behaviour and morphology.     

Polymorphisms in the nucleotide excision repair gene ERCC2/XPD and risk of non-Hodgkin lymphoma

Non-Hodgkin lymphoma (NHL) represents a complex group of B- and T-cell malignancies characterised by chromosomal translocations. Since defects in DNA repair result in an increased frequency of chromosomal aberrations it has been hypothesised that genetic variation in DNA repair may be associated with risk of NHL. To investigate the relationship between DNA repair and NHL we analysed polymorphisms in XPD (R156R, D312N, K751Q) using DNA collected in a UK population-based case-control study of lymphoma. We observed no association between genetic variation in XPD and risk of NHL. However, the XPD 751 Gln allele was associated with a two-fold decreased risk of diffuse large B-cell lymphoma (OR 0.56, 95% CI 0.34–0.92, p = 0.02), the major subtype of NHL. Overall, our study identifies that XPD polymorphisms may be important in the aetiology of NHL although analysis of additional polymorphisms and extended haplotype studies are required to clarify their role.     

Parental risk factors and anorectal malformations: systematic review and meta-analysis

Background

Anderson's disease (AD) or chylomicron retention disease (CMRD) is a very rare hereditary lipid malabsorption syndrome. In order to discover novel mutations in the SAR1B gene and to evaluate the expression, as compared to healthy subjects, of the Sar1 gene and protein paralogues in the intestine, we investigated three previously undescribed individuals with the disease.

Methods

The SAR1B, SAR1A and PCSK9 genes were sequenced. The expression of the SAR1B and SAR1A genes in intestinal biopsies of both normal individuals and patients was measured by RTqPCR. Immunohistochemistry using antibodies to recombinant Sar1 protein was used to evaluate the expression and localization of the Sar1 paralogues in the duodenal biopsies.

Results

Two patients had a novel SAR1B mutation (p.Asp48ThrfsX17). The third patient, who had a previously described SAR1B mutation (p.Leu28ArgfsX7), also had a p.Leu21dup variant of the PCSK9 gene. The expression of the SAR1B gene in duodenal biopsies from an AD/CMRD patient was significantly decreased whereas the expression of the SAR1A gene was significantly increased, as compared to healthy individuals. The Sar1 proteins were present in decreased amounts in enterocytes in duodenal biopsies from the patients as compared to those from healthy subjects.

Conclusions

Although the proteins encoded by the SAR1A and SAR1B genes are 90% identical, the increased expression of the SAR1A gene in AD/CMRD does not appear to compensate for the lack of the SAR1B protein. The PCSK9 variant, although reported to be associated with low levels of cholesterol, does not appear to exert any additional effect in this patient. The results provide further insight into the tissue-specific nature of AD/CMRD.     

Gastric Burkitt's lymphoma. Case report and review of the literature

A case of gastric Burkitt's lymphoma with pancreatic infiltration in a 15-year-old boy is reported. Local lymph nodes were not involved. Review of the literature disclosed that the reported cases of Burkitt's lymphoma were localized in the intestine. The origin, evolution and prognosis of gastrointestinal lymphoma are briefly discussed.     

Zinc supplementation and cardiovascular disease risk factors: A GRADE-assessed systematic review and dose-response meta-analysis

Background and objectiveA deficit in zinc has been related to a higher probability of developing cardiovascular diseases (CVDs). The anti-inflammatory and anti-oxidative capabilities of zinc may have a wide range of therapeutic impacts on CVDs. We conducted a comprehensive systematic review and meta-analysis of the possible impacts that zinc supplementation may have on the risk factors associated with CVDs.MethodsTo identify eligible randomized clinical trials (RCTs) evaluating the effects of zinc supplementation on CVDs risk factors, electronic databases including PubMed, Web of Science, and Scopus were systematically searched up to January 2023. The heterogeneity of trials was checked using the I² statistic. According to the heterogeneity tests, random effects models were estimated and pooled data were defined as the weighted mean difference (WMD) with a 95% confidence interval (CI).ResultsOf 23165 initial records, 75 studies that met inclusion criteria were analyzed in this meta-analysis. The pooled findings indicated the significant lowering effects of zinc supplementation on triglycerides (TG), total cholesterol (TC), fasting blood glucose (FBG), Hemoglobin A1C (HbA1C), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), C-reactive protein (CRP), interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α), nitric oxide (NO), malondialdehyde (MDA), total antioxidant capacity (TAC), and glutathione (GSH), with no noticeable effects on low-density lipoprotein (LDL), high-density lipoprotein (HDL), insulin, systolic blood pressure (SBP), diastolic blood pressure (DBP), aspartate transaminase (AST), and Alanine aminotransferase (ALT).ConclusionOverall, zinc supplementation may boost recognized coronary risk factors that contribute to the development of CVDs. Future research should be conducted to bolster our results.