Risk Of NHL Research Articles

Association of LIN28B Gene Polymorphisms (rs221634, rs221635, rs314276, rs9404590, and rs12194974) with Non-Hodgkin Lymphoma Susceptibility and Clinical/Pathological Features.

Lymphoma is a common hematopoietic cancer. It has been proposed that LIN28B gene and its variations may have function in cancer progression and metastasis. Therefore, the purpose of this investigation has been to examine the correlation among LIN28B gene polymorphisms (such as rs221634 A>T, rs221635 T> C, rs314276 C>A, rs9404590 T>G, and rs12194974 G>A) as well as the risk of NHL in an Iranian sample. In the current case-control research, 175 individuals with Non-Hodgkin Lymphoma along with 175 normal controls participated; polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology has been utilized to the genotype samples. Our data demonstrated that rs12194974 and the rs221635 variants have been correlated with higher NHL risk, while rs221634 and rs314276 variants were correlated with lower risk of NHL (P≤0.05). In addition, we detected an association between rs221634 and treatment with R-CHOP. No substantial correlation has discovered among rs9404590 polymorphism and NHL in any inheritance models (P≥0.05). This was the first investigation evaluating the correlation among LIN28B gene polymorphisms as well as the occurrence of NLH. Further studies in different ethnic populations and large-scale sample size are needed to support results.

Are interleukin 17 and interleukin 23 inhibitors associated with malignancies?-Insights from an international population-based study.

Cancer risk after long-term exposure to interleukin (IL)-23 inhibitors (IL-23i) and IL-17 inhibitors (IL-17i) remains to be delineated. To evaluate the risk of malignancies in patients with psoriasis treated with IL-23i and IL-17i relative to those prescribed tumour necrosis factor inhibitors (TNFi) during the first 5 years following drug initiation. A global population-based cohort study included two distinct analyses comparing patients with psoriasis under different therapeutic modalities; (i) new users of IL-17i(n = 15,331) versus TNFi (n = 15,331) and (ii) new users of IL-23i (n = 5832) versus TNFi (n = 5832). Patients prescribed IL-17i experienced a decreased risk of non-Hodgkin lymphoma (NHL; HR, 0.58; 95% CI, 0.40-0.82; p = 0.002), colorectal cancer (HR, 0.68; 95% CI, 0.49-0.95; p = 0.024), hepatobiliary cancer (HR, 0.68; 95% CI, 0.58-0.80; p < 0.001), ovary cancer (HR, 0.48; 95% CI, 0.29-0.81; p = 0.005), melanoma (HR, 0.52; 95% CI, 0.37-0.73; p < 0.001), and basal cell carcinoma (BCC; HR, 0.57; 95% CI, 0.48-0.67; p < 0.001). IL-23i was associated with a reduced risk of NHL (HR, 0.39; 95% CI, 0.19-0.78; p = 0.006), hepatobiliary cancer (HR, 0.44; 95% CI, 0.31-0.62; p < 0.001) and BCC (HR, 0.76; 95% CI, 0.57-0.99; p = 0.046). In a sensitivity analysis comparing patients managed by IL-17i and IL-23i with their biologic-naïve counterparts, these classes were associated with decreased risk of several malignancies. IL-17i and IL-23i are associated with decreased risk of several malignancies. These findings should be considered prior to the prescription of biologics.

Association between cumulative airborne dioxin exposure and non-Hodgkin's lymphoma risk in a nested case-control study within the French E3N cohort

BackgroundDioxins are a family of chemical molecules that are chlorinated, lipophilic, and bio-accumulative. They are thought to enhance the risk of non-lymphoma Hodgkin's due to their known carcinogenic properties (NHL). This is the first epidemiological research to investigate the relationship between repeated emissions of airborne dioxin exposure and the risk of NHL. ObjectiveA case-control study nested within the French E3N cohort of 98,995 women covered by the health insurance provider of the national education system evaluated the association between cumulative airborne dioxin exposure and NHL risk. Materials and methodsNHL incident cases (368) and controls (368) were compared. Over the duration of the study, participants' residential histories and the locations of industrial sites were gathered (1990–2008). Using a Geographic Information System (GIS)-based exposure index, the cumulative exposure to airborne dioxins for each participant was calculated at the individual address level. The odds ratios (OR) and 95 % confidence intervals (CI) were calculated using multivariable conditional logistic regression models (CI). ResultsThe log-transformed continuous cumulative dioxin exposure index was substantially correlated with the risk of NHL (OR1.2 (95 % CI 1.0,1.4) for an increase in log-TEQ/m2 of 4.4, or one standard deviation). The combined chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) subtype was significantly associated with NHL histological subtypes (OR 1.6 (95 % CI 1.1,2.3)). ConclusionThe findings of this study demonstrate a significant positive correlation between cumulative airborne dioxin exposure and the risk of NHL in women, and more specifically, a significant positive association for the CLL & SLL subtype. These results help to support the attempts to reduce the exposure to dioxins in the air.

Blood Leukocyte AHRR Methylation and Risk of Non-smoking-associated Cancer: A Case-cohort Study of Non-Hodgkin Lymphoma.

Our population-based study demonstrated that lower AHRR methylation levels in peripheral blood leukocytes were associated with an increased risk of NHL. This association was independent of tobacco smoking, sex, and lifestyle characteristics, but was highly dependent on time to diagnosis. These findings highlight the potential of AHRR methylation as a biomarker for NHL risk, effective up to 10 years after blood draw.

495 Radon and Fracking Exposures and Lymphoma Risk in a Canine Model of non-Hodgkin Lymphoma

OBJECTIVES/GOALS: The objective of this study was to determine whether residential radon and proximity to horizontal oil and drilling (fracking) are risk factors for the development of multicentric lymphoma in pet dogs, a spontaneous, immunocompetent model for non-occupational risk for NHL in humans. METHODS/STUDY POPULATION: Two case-control populations of dogs with multicentric lymphoma were utilized, with a focus on two dog breeds at high risk for lymphoma. Control dogs were matched for age, breed, and sex. Home addresses were collected for 54 Golden retrievers with lymphoma and 108 Golden retriever controls, and for 56 boxer dogs with lymphoma and 84 unaffected boxer controls. Counties of residence were matched to radon zones and percentage of home radon tests that exceeded the actionable level of 4 pCi/L, available by county through the EPA and the CDC National Environmental Public Health Tracking Network from 2008 to 2017. Locations of horizontal oil and gas wells were obtained from the Enverus Database, and distances from dog homes to the closest well, and well density by county, were calculated for each case and control. RESULTS/ANTICIPATED RESULTS: We found no significant differences in radon zones, county level radon measurements, or residential proximity to active fracking wells between dogs with lymphoma and unaffected controls in either the Golden Retriever or boxer populations. DISCUSSION/SIGNIFICANCE: Canine multicentric lymphoma resembles human NHL and is a valuable model of non-occupational environmental risk for NHL in people. Although we did not find geographic associations between radon and fracking wells, follow-up studies will measure household radon, as well as household air, water, and dog urine for potentially genotoxic chemicals.

Age-period-cohort analysis of gender differential trends in incidence and mortality of non-Hodgkin lymphoma in China, 1990-2019.

Non-Hodgkin lymphoma (NHL) is one of the dominant malignancies in the hematological system. This study estimated secular trends in NHL incidence and mortality from 1990 to 2019 and provided comprehensive evaluations of potential age, period, and cohort effects. Age-period-cohort (APC) model was used to analyze changes in NHL incidence and mortality with age, period, and birth cohort effects based on data from the Global Burden of Disease Study 2019. The age-standardized incidence rates (ASIR) of NHL rose by 144.6% and age-standardized mortality rate (ASMR) rose by 27.5% from 1990 to 2019. Local drift for incidence was greater than 0 (p< 0.05) for both genders in each age group. Local drift for mortality rates were greater than 0 (p< 0.05) for males aged 20 to 89 years and females aged 60 to 84 years and less than 0 (p< 0.05) for females aged 20 to 50 years. Period rate ratio (RR) and cohort RR of NHL incidence in China showed an increasing trend, while the trend of male and female mortality was not consistent. NHL incidence and mortality rates have been increasing in China over the past three decades. Males and older individuals were at high risk for NHL. Thus, attention to the prevention and therapy of NHL would be essential to lessen the disease burden of NHL.

Risk of non-Hodgkin lymphoma in breast cancer survivors: a nationwide cohort study

Several studies have suggested that estrogens have a protective function against lymphomagenesis. The treatment of breast cancer is driven by subtype classification, and the assessment of hormone receptor status is important for treatment selection. Thus, we evaluated the association between breast cancer and the incidence of NHL. We conducted a retrospective cohort study using a population-based nationwide registry in South Korea. We selected all women with newly diagnosed breast cancer between January 1st, 2002 and December 31st, 2016 who received curative treatment (N = 84,969) and a 1:10 sample of age-matched non-breast cancer controls (N = 1,057,674). Incident breast cancer (time-varying exposure) was the exposure and development of any type of NHL, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mature T/NK-cell lymphomas, anaplastic large cell lymphoma (ALCL), and unspecified types of NHL, was the outcome. During follow-up, 1564 incident cases of NHL occurred. The fully adjusted Hazard Ratio (HR) for NHL associated with the development of breast cancer was 1.64 (95% CI = 1.34–2.00) after adjusting for body mass index, alcohol intake, physical activity, smoking, income, and comorbidity. The adjusted HR for NHL was much higher in participants who were aged <50 years and who received hormone therapy (either tamoxifen or aromatase inhibitors) than in those ≥50 years or who did not receive hormone therapy, respectively. The development of breast cancer was associated with a significantly increased risk of NHL, particularly follicular lymphoma and mature T/NK-cell lymphoma. In particular, the risk of NHL was higher in patients receiving hormone therapy and in younger patients.

Risk of hematologic malignancies after breast ductal carcinoma in situ treatment with ionizing radiation

The increased incidence of secondary hematologic malignancies (SHM) is a well-known, potentially fatal, complication after cancer treatment. It is unknown if patients with ductal carcinoma in situ (DCIS) of the breast treated with external beam radiotherapy (RT) and who survive long-term have increased risks of secondary hematologic malignancies (SHM), especially for low/intermediate-risk subsets with limited benefits from RT. DCIS patients in Surveillance, Epidemiology, and End Results (SEER) registries (1975–2016) were identified. Relative risks (RR), hazard ratio (HR), and standardized incidence ratios (SIR) were calculated to assess the SHM risk and subsequent survival times. SHM development, defined as a nonsynchronous SHM occurring ≥1 year after DCIS diagnosis, was our primary endpoint. Of 184,363 eligible patients with DCIS, 77,927 (42.3%) in the RT group, and 106,436 (57.7%) in the non-RT group, 1289 developed SHMs a median of 6.4 years (interquartile range, 3.5 to 10.3 years) after their DCIS diagnosis. Compared with DCIS patients in the non-RT group, RT was associated with increased early risk of developing acute lymphoblastic leukemia (ALL; hazard ratio, 3.15; 95% CI, 1.21 to 8.17; P = 0.02), and a delayed risk of non-Hodgkin lymphoma (NHL; hazard ratio, 1.33; 95% CI, 1.09 to 1.62; P < 0.001). This increased risk of ALL and NHL after RT was also observed in subgroup analyses restricted to low/intermediate-risk DCIS. In summary, our data suggest that RT after breast conserving surgery for DCIS patients should be cautiously tailored, especially for low and intermediate-risk patients. Long-term SHM surveillance after DCIS diagnosis is warranted.

Drs. Wang and Shieh reply

We appreciate the opinions shown in the letter from Liang, et al1. First, in the methods, we wrote “patients with previous cancer or other specific autoimmune disease…that might influence the risk of NHL were excluded”2.

Immune System Deregulation Predicts Outcome in Diffuse Large B Cell Lymphoma (DLBCL)

Background: Treatment failure after RCHOP is associated with poor outcome in DLBCL. Despite considerable immune system variation among individual patients, the diagnostic absolute monocyte (AMC) and absolute lymphocyte (ALC) counts can reproducibly separate DLBCL patients with different outcomes. In addition, polymorphisms in immune regulating cytokines are associated with NHL risk and cytokine deregulation can predict response to RCHOP. This suggests distinct patterns of immune system deregulation in DLBCL which may serve to guide prognosis and therapy. Aim: To investigate immune cell and cytokine deregulation in DLBCL. Methods: Diagnostic AMC and ALC from 116 DLBCL patients and 111 healthy stem cell donors were assessed. 20 cytokines were measured in duplicate in serum samples from 34 DLBCL patients with known outcome and 11 health donors using the mesoscale discovery (MSD) electrochemiluminescence platform. The 10 most deregulated cytokines were measured in duplicate in 30 additional DLBCL patients. Peripheral blood mononuclear cells (PBMCs) were analysed by mass cytometry (MC) from 33 of these patients with a myeloid focused panel (29 markers) and from 27 with a T cell directed panel (28 markers). A standard control healthy donor sample was acquired with each MC batch. The OMIQ platform was used for gating and high dimensional data analysis. Results: In DLBCL median AMC was higher (p&amp;lt;0.0001) and ALC lower (p=0.0036). The AMC and ALC prognostic score separated DLBCL into 3 groups with distinct outcomes (p&amp;lt;0.0001), independent of cell of origin (COO). 8/20 cytokines were significantly elevated in DLBCL (p&amp;lt;0.05). IL-1RA (p=0.025), IL-6 (p=0.0002), IL-10 (p=0.01), MIP-1a (p=0.003) and TNF (p=0.0056) were significantly more elevated in DLBCL patients who subsequently had relapse/refractory (R/R) disease within 12 months of RCHOP (n=15) compared to those with ongoing remission &amp;gt; 24 months (CR) (n=46). After MC acquisition and normalization, PBMC populations were assessed as a percentage of CD45+ events by outcome (n=33). CD14+ monocytes were higher and CD3+ T cells lower at diagnosis in DLBCL with R/R disease (p&amp;lt;0.05). CD4+ T cells, CD8+ T cells, CD19+ B cells, NK, NKT and DC were not significantly different. Unsupervised clustering with FlowSOM followed by differential abundance analysis using edgeR was performed to dissect the PBMC populations above into subpopulations. This identified 3 classical monocyte clusters and 1 CD8+ T cell cluster associated with R/R DLBCL (-log10 FDR &amp;gt;1.3). The classical monocyte clusters all expressed the myeloid markers CD11b, CD31, CD33, SIRPa (CD172a) and CCR2 (CD192), the Fc gamma receptors CD32 and CD64 and the activation marker CD38. 2 clusters expressed HLA-DR and CD206 and were differentiated by CD13+ (cluster09) or CD40/CD86+ (cluster23). The other cluster had a suppressor phenotype with low HLA-DR and expressed CD163 and CD184 (cluster12). The differentiating T cell cluster was a CD45RA-CCR7- CD8 effector memory population (Tem) with an EM3 phenotype (CD27-, CD28-) and T-bet, cytotoxic marker (granzyme, perforin) and PD-1 expression (cluster10). To identify co-deregulated immune cell / cytokine relationships in DLBCL contributing to R/R disease we used correlation analysis across PBMC populations, differentiating clusters and cytokine levels. CD14+ correlated positively with cluster9 (classical monocyte), cluster10 (Tem), IL-1RA, IL-6, and MIP-1a (p&amp;lt;0.05). CD3+ and CD4+, but not CD8+ correlated negatively with IL-1RA, IL-6 and MIP-1a (p&amp;lt;0.05). Cluster9 and cluster10 both correlated negatively with CD3+ and CD4+, but not with each other or cytokine levels. PBMC populations, differentiating clusters, and cytokine levels were not significantly different based on cell COO, except for IL-1RA which was elevated in non-GCB type (p=0.0148). Conclusion: We find deregulated immune cell and cytokine production in DLBCL, which is associated with R/R disease and largely independent of COO. Immune profiling with MC identified 3 distinct classical monocyte clusters and 1 CD8 Tem cluster associated with subsequent relapse. These differentiating clusters likely reflect immune dysfunction and contribute to the prognostic nature of the AMC / ALC. Further ongoing work is assessing which immune are cells secreting the most deregulated cytokines, with the aim of identifying biomarkers and targetable pathways. Disclosures No relevant conflicts of interest to declare.

Occupational Pesticide Use and Risk of Non-Hodgkin Lymphoma

Background. Evidence on the human health effects of pesticides is needed to inform risk assessment.Methods. We conducted a large study of the relationship between occupational pesticide use and risk of non-Hodgkin lymphoma (NHL, including chronic lymphocytic leukemia and multiple myeloma) by pooling data from nine case-control studies participating in the InterLymph Consortium, including 7909 cases and 8644 controls from North America, the European Union, and Australia. Pesticide use was coded using a combination of self-report and expert assessment, for pesticide active ingredients (e.g., DDT, diazinon, 2,4-D, glyphosate) and chemical groups (e.g., organophosphate (OP) insecticides, phenoxy herbicides). We estimated the association between each exposure and risk of NHL using logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CI), with adjustment for age, gender, race, socioeconomic status, study location, and any pesticide use – for NHL, and separately for NHL subtypes.Results. OP insecticides were associated with increased risk of NHL. In particular, there was 43% higher risk associated with diazinon use (vs. never, 95% CI: 1.02, 2.00) and the association was stronger with longer duration (e.g., highest tertile duration vs. never, OR=2.40, 95% CI: 1.20, 4.78). We found no association between all NHL and pyrethroid insecticides or DDT. The phenoxy herbicide, 2,4-D, was associated with increased risk of NHL, and risk was most elevated for use within 20 years of diagnosis (i.e., unlagged) (e.g., ever vs. never: unlagged, OR=1.56, 95% CI: 1.06, 2.28; lagged, OR=1.23, 95% CI: 0.96, 1.56). Glyphosate use was not associated with risk of all NHL, but there were statistically significant risk increases for some NHL subtypes, specifically follicular lymphoma and NOS/unknown pathology.Conclusions. Our consortium-based pooled study produced evidence on potential carcinogenicity of certain pesticides. These findings are important because farming occupation and pesticides are among few leads for environmental causes of NHL.

The Influence of GPX1 Pro198Leu, CAT C262T and MnSOD Ala16Val Gene Polymorphisms on Susceptibility for Non-Hodgkin Lymphoma and Overall Survival Rate at Five Years from Diagnosis

Abstract Objective: The aim of the current study was to investigate possible associations between catalase C262T (CAT C262T), glutathione peroxidase 1 Pro198Leu (GPX1 Pro198Leu), manganese superoxide dismutase Ala16Val (MnSOD Ala16Val) gene polymorphisms and non-Hodgkin Lymphoma risk (NHL) in a Romanian population and the five-year overall survival rate of the NHL patients. Methods: We included in this case-control study 406 individuals, divided into two groups: the control group (n=315) and the patients group (n=91). The DNA was extracted from peripheral blood and amplified using specific techniques. Results: The variant homozygous genotype of GPX1 Pro198Leu represents a risk factor for NHL development and no associations regarding the risk for NHL were found for MnSOD Ala16Val and CAT C262T gene polymorphisms. Two of the studied polymorphisms were associated with the overall survival rate thus: negative association regarding MnSOD Ala16Val, associated with higher overall survival rate and a positive one regarding CAT C262T, associated with lower overall survival rate. Conclusions: According to our results, the mentioned polymorphisms may be considered as susceptible markers of the five-year overall survival rate for NHL patients. Future studies with a larger number of patients are needed to confirm our results.

Alcohol consumption and risk of hematological malignancies: A meta-analysis of prospective studies.

Current convincing evidence suggests that alcohol intake increases the risk of several carcinomas, which might subsequently lead to a recommendation toward limiting alcohol consumption. However, there are accumulating data worth meta-analyzing that show a different effect on the risk of hematological malignancies. Eligible cohort studies were sought in PubMed database up to August 31, 2016. Separate analyses were performed by subtype of hematological malignancy (non-Hodgkin lymphoma [NHL] and subtypes, Hodgkin lymphoma [HL], leukemia and subtypes), time status (ever, current, former), level of consumption (light, moderate, heavy), alcoholic beverage (total alcohol, beer, liquor, wine) and gender. Moderate and heavy alcohol consumption were significantly associated with reduced risk of NHL (relative risk [RR] = 0.85, 95% confidence interval [CI]: 0.80-0.90 and RR = 0.73, 95%CI: 0.60-0.89, respectively); a protective trend was also shown for light alcohol intake (RR = 0.93, 95%CI: 0.87-1.00). Specifically, beer consumption was associated with reduced NHL risk (RR = 0.88, 95%CI: 0.81-0.95). However, the association regarding other alcoholic beverages seemed null. The beneficial effects of alcohol mainly pertained to Diffuse Large B-Cell Lymphoma (DLBCL) (RR = 0.83, 95%CI: 0.77-0.89) and Follicular Lymphoma (FL) (RR = 0.85, 95%CI: 0.78-0.93). There was also no association between alcohol consumption and risk of HL or leukemias. In contrast to most solid malignancies, alcohol seems to confer a protective effect on NHL risk, especially on DLBCL and FL subtypes, with beer being notably beneficial.

Differences in Virological and Immunological Risk Factors for Non-Hodgkin and Hodgkin Lymphoma.

Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) are increased in populations with immune dysfunction, including people living with HIV; however, there is little evidence for to what degree immunological and virological factors differently affect NHL and HL risk. Data from the Data Collection on Adverse events of Anti-HIV Drugs Study cohort were analyzed to identify independent risk factors for NHL and HL using hazard ratios (HRs), focusing on current and cumulative area under the curve (AUC) measures of immunological and virological status. Variables with different associations with NHL and HL were identified using marginal Cox models. All statistical tests were two-sided. Among 41 420 people followed for 337 020 person-years, 392 developed NHL (incidence rate = 1.17/1000 person-years of follow-up [PYFU], 95% confidence interval [CI] = 1.06 to 1.30) and 149 developed HL (incidence rate = 0.44/1000 PYFU, 95% CI = 0.38 to 0.52). Higher risk of both NHL and HL was associated with lower current CD4 cell count (adjusted HR [aHR] of NHL for CD4 <100 vs > 599 cells/mm3 = 8.08, 95% CI = 5.63 to 11.61; HL = 4.58, 95% CI = 2.22 to 9.45), whereas higher current HIV viral load (aHR of NHL for HIV-VL >1000 vs < 50 copies/mL = 1.97, 95% CI = 1.50 to 2.59) and higher AUC of HIV-VL (aHR of NHL for highest vs lowest quintile = 2.91, 95% CI = 1.92 to 4.41) were associated with NHL only. Both current and AUC of HIV-VL were factors that had different associations with NHL and HL, where the hazard ratio for NHL was progressively higher than for HL with increasing HIV-VL category. Lower current CD4 cell count had a strong but similar association with both NHL and HL. CD4 depletion increased risk of both types of lymphomas while current and accumulated HIV-VL was associated with NHL only. This suggests that NHL development is related to both CD4 cell depletion and added immune dysfunction derived from ongoing HIV replication. This latter factor was not associated with HL risk.

Occupational ultraviolet exposure and risk of non-Hodgkin’s lymphomas: a meta-analysis

Non-Hodgkin lymphoma is a heterogeneous group of lympho-proliferative disorders. We performed a meta-analysis to summarize the available evidence from case-control studies and cohort study on the inconsistent association between occupational sun exposure and the risk of non-Hodgkin lymphoma. We searched PubMed, ISI web of science, the Cochrane Library, EMBASE and reference lists for relevant articles. Study specific odds ratios or relative risk and 95% confidence intervals were pooled by using fixed-effects or random-effects models. Ten case-control studies and one cohort study were included in the meta-analysis. Overall, the pooled odds ratios for occupational ultraviolet exposure and non-Hodgkin lymphoma risk was 1.15(95% confidence intervals: 0.99, 1.32; I2 = 44.4%). Occupational sun exposure was positively associated with the risk of NHL 1.14 (95% confidence intervals: 1.05, 1.23; I2=25.4% p for heterogeneity =0.202) in Caucasian population. Common subtypes of non-Hodgkin lymphoma and ultraviolet exposure had the negative results. The pooled odds ratios was 1.16, (95%confidence intervals: 0.90, 1.50) for T-cell non-Hodgkin lymphoma; 0.79, (95%confidence intervals: 0.61, 1.02) for B-cell non-Hodgkin lymphoma; 1.13, (95%confidence intervals: 0.96, 1.34) for chronic lymphocytic leukemia; 1.25, (95%confidence intervals: 0.95, 1.64) for males; 1.49, (95%confidence intervals: 0.99, 2.25) for females. Data suggested that occupational ultraviolet exposure was a risk factor for non-Hodgkin lymphoma in Caucasian population. While, there had no relationship between occupational ultraviolet exposure and risk of non-Hodgkin lymphoma in general population as well as non-Hodgkin lymphoma common subtypes. Besides, gender specific occupational sun exposure also indicated no association on risk of non-Hodgkin lymphoma.

Consecutive stimulation of HBsAg promotes the viability of the human B lymphoblastoid cell line IM-9 through regulating the SIRT1-NF-κB pathway.

Patients with chronic HBV infection have been reported to suffer a significantly increased risk of NHL, but the underlying mechanisms remain to be clearly explained. The aim of the present study was to clarify the relationship between chronic HBV infection and NHL development. Fluorescence-activated cell sorting, Annexin V/7-aminoactinomycin D staining and MTS assay were used to analyze the rate of apoptosis and cell viability. In addition, western blotting was used to detect protein expression. The effects of the activator of SIRT1, SRT1720, and the inhibitor of SIRT1, nicotinamide, were also analyzed. The expression levels cytokines and chemokines were determined by multiplex assay. Hepatitis B surface antigen (HBsAg) was demonstrated to increase the viability of the human peripheral B lymphoblastoid cell line, IM-9, in a dose- and time-dependent manner. HBsAg also decreased histone H3 acetylation and p21 expression at the molecular level. HBsAg upregulated the expression of anti-apoptotic B-cell lymphoma-extra-large and B-cell lymphoma 2 proteins, and inactivated the intrinsic apoptosis pathway by reducing BCL2 associated X, apoptosis regulator expression and increasing the expression of sirtuin 1 (SIRT1) and nuclear factor-κB (NF-κB). HBsAg also altered the levels of certain chemokines and cytokines, including interleukin (IL)-4, -10 and -12, C-X-C motif chemokine 10 and C-C motif chemokine ligand 5. Inhibition of SIRT1 suppressed the effects induced by HBsAg. The anti-apoptotic effect of HBsAg in IM-9 cell lines occurred via the promotion of cell viability, inhibition of apoptosis, regulation of chemokines and cytokines, acetylation of histone H3 and alteration of SIRT1 and NF-κB expression. In conclusion, chronic stimulation with HBsAg promoted the viability of the human B lymphoblastoid cell line, IM-9, through regulation of the SIRT1-NF-κB pathway. This may be an underlying mechanism of HBV-associated NHL.

Annals for Educators - 3 January 2017

Annals for Educators - 3 January 2017

Systematic review and meta-analysis of glyphosate exposure and risk of lymphohematopoietic cancers

ABSTRACTThis systematic review and meta-analysis rigorously examines the relationship between glyphosate exposure and risk of lymphohematopoietic cancer (LHC) including NHL, Hodgkin lymphoma (HL), multiple myeloma (MM), and leukemia. Meta-relative risks (meta-RRs) were positive and marginally statistically significant for the association between any versus no use of glyphosate and risk of NHL (meta-RR = 1.3, 95% confidence interval (CI) = 1.0–1.6, based on six studies) and MM (meta-RR = 1.4, 95% CI = 1.0–1.9; four studies). Associations were statistically null for HL (meta-RR = 1.1, 95% CI = 0.7–1.6; two studies), leukemia (meta-RR = 1.0, 95% CI = 0.6–1.5; three studies), and NHL subtypes except B-cell lymphoma (two studies each). Bias and confounding may account for observed associations. Meta-analysis is constrained by few studies and a crude exposure metric, while the overall body of literature is methodologically limited and findings are not strong or consistent. Thus, a causal relationship has not been established between glyphosate exposure and risk of any type of LHC.

Primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is a relatively common autoimmune systemic rheumatic disease. In addition to sicca syndrome and swollen salivary glands, systemic features manifest in the majority of patients, and are severe in 15%, particularly affecting the joints, skin, lungs, and peripheral nervous system. A recent meta-analysis estimated a pooled relative risk of 13.76 for the development of non-Hodgkin lymphoma, particularly in pSS patients who have parotid enlargement, vasculitis, cryoglobulinemia, and antibodies to Ro and La. pSS is the underlying diagnosis in one-third of mothers of neonates affected by congenital heart block. The diagnosis of pSS is complex and requires a stepwise approach to evaluate symptoms of ocular and oral dryness, objective measures of lacrimal and salivary gland dysfunction, and evidence of autoimmunity with Ro/La autoantibodies and labial salivary gland biopsy. It is essential to eliminate other autoimmune diseases, as well as non-autoimmune causes of sicca syndrome, such as menopause, endocrine diseases, anticholinergic effects of drugs, and fibromyalgia, to delineate pSS patients who are at risk of systemic complications. Recent major advances in the diagnosis of pSS have been the development of classification criteria, which serve as a template for clinical diagnosis, and outcome measures for use in clinical trials and prospective patient cohorts. Clinical data and biological samples from longitudinal cohorts, embedded into clinical practice, will be essential to further improve the diagnosis and management of pSS, increase knowledge about the natural history of the disease, gain insights into its pathogenesis, and stratify patients according to their risk of systemic disease and NHL. At present, there is a gap in evidence regarding the role of structured protocols in the management of pSS. Recent recommendations for the management of sicca symptoms and clinical trials of disease-modifying therapy are discussed.

Burkitt’s lymphoma Associated with HIV Infection

Non-Hodgkin lymphoma of the B-cell type is the second most common neoplasm in patients with human immunodeficiency virus infection after Kaposi's sarcoma. The majority of the cases of non-Hodgkin lymphoma associated with the acquired immunodeficiency syndrome involve extranodal sites, specially the digestive tract, including the oral cavity and the central nervous system. The estimated relative risk of NHL associated HIV infection is 100 times greater than in general population and this risk increases with the progressive immunosuppression related to the retrovirus Burkitt's lymphoma has frequently been reported as a neoplasm in HIV infected patients. These lymphomas are now better designed as AIDS-related BL.