Risk Of non-Hodgkin Lymphoma Research Articles

Risk of lymphohematologic malignancies in patients with chronic plaque psoriasis: A systematic review with meta-analysis

The association between chronic plaque psoriasis and lymphohematologic malignancies (LHMs) remains controversial. To investigate the risk of LHMs in patients with psoriasis according to the best evidence. A systematic review and meta-analysis of observational cohort studies was undertaken to assess the association of psoriasis with different LHMs. A literature search for relevant studies was performed on February 28, 2021. The random-effects model in conducting meta-analyses was applied. To evaluate the risk of bias, the Newcastle-Ottawa Scale was employed. A total of 25 observational studies were selected, comprising collectively 2,501,652 subjects. A significantly increased risk for LHM (hazard ratio [HR], 1.55; 1.24-2.94) and lymphoma (HR, 1.27; 1.08-1.50) in patients with moderate-to-severe plaque psoriasis compared to the general population was found. In detail, increased risks for Hodgkin lymphoma (HR, 1.71; 1.27-2.30), non-Hodgkin lymphoma (HR, 1.27; 1.08-1.50), multiple myeloma (HR, 1.32; 1.03-1.69), and leukemia (HR, 1.28; 1.00-1.65) were found. The risk of cutaneous T-cell lymphoma was markedly augmented in patients with psoriasis (HR, 6.22; 3.39-11.42). Possible ascertainment bias related to the diagnosis of LHMs. The increased risk of LHMs, particularly cutaneous T-cell lymphoma, in patients with psoriasis could be related to exposure to systemic immunosuppressive therapies, comorbidities, and sustained immune activation, particularly in the skin.

Occupational insecticide exposure and risk of non-Hodgkin lymphoma: A pooled case-control study from the InterLymph Consortium.

Evidence for the human health effects of pesticides is needed to inform risk assessment. We studied the relationship between occupational insecticide use and risk of non-Hodgkin lymphoma (NHL) 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. Insecticide use was coded using self-report or expert assessment, for insecticide groups (eg, organophosphates, pyrethroids) and active ingredients (eg, malathion, permethrin). Associations with insecticides were estimated using logistic regression to produce odds ratios (ORs) and 95% confidence intervals (CI) for all NHL and NHL subtypes, with adjustment for study site, demographic factors and use of other pesticides. Occupational insecticide use, overall, was not associated with risk of NHL. Use of organophosphate insecticides was associated with increased risk of all NHL and the subtype follicular lymphoma, and an association was found with diazinon, in particular (ever use: OR=2.05, 95%CI: 1.24-3.37). The carbamate insecticide, carbaryl, was associated with risk of all NHL, and the strongest associations were found with T-cell NHL for ever-use (OR=2.44, 95%CI: 1.13-5.28) and longer duration (>8 years vs never: OR=2.90, 95%CI: 1.02-8.25). There was no association of NHL with other broad groups of insecticides, including organochlorines and pyrethroids, and some inverse associations were estimated in relation to historical DDT use. Our findings contribute to the totality of evidence available to help inform risk decisions by public health and regulatory agencies of importance given continued, widespread use of organophosphate and carbamate insecticides.

Epidemiology of Amyloidosis and Genetic Pathways to Diagnosis and Typing

We reviewed our studies on epidemiology and germline genetics of amyloidosis. In epidemiology, we considered both hereditary and non-hereditary amyloidosis. As the source of data, we used the nationwide Swedish hospital discharge register. We estimated the incidence of hereditary ATTR amyloidosis, for which Sweden is a global endemic area, at 2/million. Surprisingly, the disease was also endemic within Sweden; the incidence in the province with the highest incidence was 100 times higher than in the rest of Sweden. Risk of non-Hodgkin lymphoma increased five-fold in the affected individuals. Among non-hereditary amyloidosis, the incidence for AL amyloidosis (abbreviated as AL) was estimated at 3.2/million, with a median survival time of 3 years. Secondary systemic amyloidosis (most likely AA amyloidosis) showed an incidence of 1.15/million for combined sexes. The female rate was two times higher than the male rate, probably relating to the higher female prevalence of rheumatoid arthritis. The median survival time was 4 years. We also identified patients who likely had familial autoinflammatory disease, characterized by early onset and immigrant background from the Eastern Mediterranean area. Young Syrian descendants had the highest incidence rate, which was over 500 times higher than that in individuals with Swedish parents. Germline genetics focused on AL on which we carried out a genome-wide association study (GWAS) in three AL cohorts (N = 1129) from Germany, UK, and Italy. Single nucleotide polymorphisms (SNPs) at 10 loci showed evidence of an association at p < 10−5; some of these were previously documented to influence multiple myeloma (MM) risk, including the SNP at the IRF4 binding site. In AL, SNP rs9344 at the splice site of cyclin D1, influencing translocation (11;14), reached the highest significance, p = 7.80 × 10−11; the SNP was only marginally significant in MM. The locus close to gene SMARCD3, involved in chromatin remodeling, was also significant. These data provide evidence for common genetic susceptibility to AL and MM. We continued by analyzing genetic associations in nine clinical profiles, characterized by organ involvement or Ig profiles. The light chain only (LCO) profile associated with the SNP at the splice site of cyclin D1 with p = 1.99 × 10−12. Even for the other profiles, distinct genetic associations were found. It was concluded that the strong association of rs9344 with LCO and t(11;14) amyloidosis offer attractive mechanistic clues to AL causation. Mendelian randomization analysis identified associations of AL with increased blood monocyte counts and the tumor necrosis factor receptor superfamily member 17 (TNFRSF17 alias BCMA) protein. Two other associations with the TNFRSF members were found. We discuss the corollaries of the findings with the recent success of treating t(11;14) AL with a novel drug venetoclax, and the application of BCMA as the common target of plasma cell immunotherapies.

Coinfection with HCV or HBV Increases the Risk of Lymphoma in HIV-Positive Patients: A Combined Analysis of the Lymphovir-ANRS-CO16 and Fhdh-ANRS-CO4 Cohorts

BACKGROUNDHuman immunodeficiency virus (HIV) infection has been linked to an increased risk of non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). In the HIV-uninfected population, hepatitis C virus (HCV) and hepatitis B virus (HBV) infections are both associated with an increased risk of NHL. Scarce data suggest an increased risk of HL in patients chronically infected with HBV. HCV and HBV coinfections are frequent among persons living with HIV (PLWHIV). The impact of HCV and HBV infections on HIV-associated lymphoma in the era of combined antiretroviral therapy (cART) deserves evaluation. METHODSWe compared the prevalence of HBV and HCV coinfections between PLWHIV with lymphoma who were enrolled in the Lymphovir French National Agency for Research on AIDS and Viral Hepatitis (ANRS)-CO16 cohort and PLWHIV enrolled in the French Hospital Database on HIV (FHDH-ANRS-CO4) with at least one follow-up visit in 2011 (n = 48 186). This cohort has been shown to be representative of PLWHIV under care in France.Lymphovir-ANRS-CO16 cohort enrolled consecutive HIV-infected individuals with lymphoma (NHL or HL) in 32 centers. The histological diagnosis was established using the 2008 WHO classification and was confirmed within the French hematopathology network (LYMPHOPATH). Finally, we analyzed the characteristics and outcomes of lymphomas in coinfected patients. RESULTSBetween 2008 and 2015, 179 patients with HIV-related lymphomas were enrolled, of whom 110 had NHL (61%) and 69 had HL (39%), The HCV serology, available for all the patients, was positive in 38 cases (29 with NHL and 9 with HL). Among 26 HCV+ patients with available data, 15 had detectable HCV RNA load at lymphoma diagnosis, five had Child-Pugh A cirrhosis, two had liver fibrosis, and one had an extrahepatic manifestation (type III cryoglobulinemia). Overall, the HCV seroprevalence was 26% among patients with NHL, a proportion significantly higher than that in the FHDH-ANRS-CO4 cohort (14%) (odds ratio (OR): 2.15, 95% confidence interval [1.35-3.32])(Table). There was no association between HCV and HL (prevalence 13%, OR: 0.90 [0.39-1.82]).The distribution of NHL subtypes among the 29 patients with HCV infection was as follows: DLBCL (n=17), MZL (n=3), plasmablastic lymphomas (n=3), primary effusion lymphoma (PEL) (n=3), BL (n=2), and T-cell lymphoma (n=1). HCV was significantly associated with DLBCL (prevalence 33%, OR: 2.91 [1.53-5.34]). Among the patients with DLBCL, 13/17 HCV+ patients had at least one site of extranodal involvement, compared to 16/34 HCV- patients (p=0.05). Four DLBCL patients received anti-HCV therapy after treatment of their lymphoma, consisting of IFN/ribavirin, either alone (n=1) or direct antiviral agents (n=3). A sustained virological reponse and a durable remission of their lymphoma were obtained in each case. Remarkably, a man with splenic MZL received anti-HCV therapy with interferon and ribavirin with no other lymphoma treatment, leading to long-lasting both virological and hematological complete responses. During follow-up, 10 deaths occurred among HCV+ patients with NHL due to progression of lymphoma (n=8) or solid tumours (n=2). With a median follow-up of 43 months, the 2-year OS among NHL patients tended to be lower in HCV+ patients (Figure).HBV status was available for 177 of the 179 lymphoma patients, of whom 15 had chronic HBV infection based on HBs Ag positivity (n=13) or HBV DNA positivity (n=2). Five patients had NHL (DLBCL (n=2) and BL (n=3)) and 10 had HL. Overall, chronic HBV infection was present in 5% of patients with NHL, which did not differ from the value of the FHDH-ANRS-CO4 cohort (7%) (OR: 0.60 [0.19-1.45]). In contrast, the prevalence of chronic HBV infection was higher among patients with HL than in the FHDH-ANRS-CO4 (14%; OR: 2.16 [0.98-4.27]). CONCLUSIONAs compared with the general cohort of HIV-infected patients, HCV coinfection was associated with an increased risk of NHL, especially DLBCL, and tended to be associated with poorer outcome. While no increase in the risk of NHL was observed among HBV coinfected patients, chronic HBV infection was associated with an increased risk of HL. Our findings suggest that chronic antigenic stimulation induced by HCV or HBV contribute to lymphomagenesis in HIV-infected patients. It paves the way for evaluation of novel therapeutic strategies based on the newest direct antiviral agents for HCV coinfected patients. [Display omitted] DisclosuresCoiffier:Celltrion, Inc: Consultancy, Honoraria. Coppo:Alexion: Consultancy, Research Funding; Ablynx: Consultancy, Research Funding; Octapharma: Consultancy.

Human Pegivirus (HPgV) Infection and Lymphoma Risk and Prognosis: A Study from North America

Background. HPgV (previously called GBV-C) is a single-stranded RNA virus belonging to the Flaviviridae, and is the most closely related human virus to the Hepatitis C virus. HPgV is transmitted through parenteral, sexual and perinatal routes and replicates in vitro in T and B-lymphocytes. Active infection lasts months to years and viremia can be detected in plasma by real time (RT)-PCR methods. HPgV viremia has been linked to risk of non-Hodgkin lymphoma in some previous studies, but these have had a limited number of cases. In the largest study conducted to date, we evaluated the association of HPgV viremia and viremic load (VL) with risk of developing lymphoma, overall and by major subtypes, in the Mayo Clinic Case-Control Study of Lymphoma. Because the virus has also been associated with better prognosis in the setting of co-infection with HIV in many studies, we further assessed the association of HPgV with prognosis. Finally, to better understand the association of HPgV with lymphoma risk we correlated the HPgV status with circulating levels of selected cytokines in a subset of our controls.Methods. To assess the role of HPgV in lymphoma risk (etiology), we used risk factor data and banked plasma samples (stored at -80°C) from 2094 lymphoma cases newly diagnosed from 2002-2009 and 1572 frequency matched controls. Plasma samples (blind to case/control status) were tested for HPgV RNA by RT-PCR, and those with RNA concentrations < 5,000 genome equivalents/ml were confirmed using nested RT-PCR methods. We used unconditional logistic regression model to estimate odds ratio (ORs) and 95% confidence intervals (CI) for the association of HPgV status (negative/positive) and VL (tertiles among positive controls) with lymphoma risk, adjusted for age and sex. To assess the role of HPgV in lymphoma outcome (prognosis), we used 2948 cases from the Iowa/Mayo Molecular Epidemiology Resource, a prospective cohort study of newly diagnosed lymphoma patients (included all cases from the case-control study). We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% CI for the association of HPgV viremia status and VL with event-free (EFS) and overall (OS) survival, adjusted for clinical and treatment variables. Circulating serum cytokines in 379 controls with HPgV data were analyzed using the Luminex-100 system Version 1.7. Data were acquired using STar Station software and analysis was performed using the MasterPlex QT 1.0 system.Results. The mean age of cases was 61 years, and 58.2% were male, while the mean age of controls was 63 years, and 51.1% were male; 78 (5.0%) controls and 211 (10.1%) cases were HPgV positive. There was a positive association of HPgV viremia with risk of lymphoma overall (OR = 2.14; 95% CI 1.63-2.80; p <0.0001), and for all major subtypes except HL and CLL/SLL (Table). Further adjustment for history of hepatitis, transfusion, autoimmune disease, atopy, family history of lymphoma, farming, obesity, smoking, alcohol use, or sun exposure did not confound these results, and results were consistent when excluding plasma samples (38%) collected after initiation of treatment. There was no dose-response association of VL with overall lymphoma risk: compared to HPgV negative, OR = 1.8 for lowest tertile (95% CI 0.58-5.97), OR = 4.3 for middle tertile (95% CI 0.97-19.6), and OR = 2.5 for highest tertile (95% CI 0.95-6.97). In the control group, median levels of serum sIL2-R (p=0.04), MIP1α (p=0.03) and MIG (p=0.02) were significantly higher in HPgV viremia positive compared to HPgV negative controls. In contrast to the analysis for risk, there was no association of HPgV viremia with EFS (HR = 1.00; 95% CI 0.85-1.18) or OS (HR = 0.97; 95% CI 0.79-1.20) for lymphoma overall, nor for any of the subtypes (Table). Likewise, there was no association of EFS or OS with viremic load.Conclusion. HPgV infection was associated with the overall risk of lymphoma, as well as most of the major NHL subtypes except CLL/SLL and HL, and this was not confounded by other lymphoma risk factors. However, there was no association of HPgV status with prognosis. Among controls, HPgV viremia was associated with higher levels of IL-2R, MIP1α and MIG, which were previously associated with risk of DLBCL and FL in a case-control analysis, and suggests potential mechanistic pathways for further exploration. These data support the hypothesis for a role for this virus in the etiology of multiple lymphoma subtypes. [Display omitted] DisclosuresNowakowski:Nanostring: Research Funding; Bayer: Consultancy, Research Funding; Abbvie: Consultancy; Genetech: Consultancy, Research Funding; Morphosys: Consultancy, Research Funding; celgene: Consultancy, Research Funding; pharmacyclics: Consultancy. Ansell:Affimed: Research Funding; Seattle Genetics: Research Funding; Bristol-Myers Squibb: Research Funding; Merck: Research Funding; Celldex: Research Funding. Cerhan:Janssen: Other: Scientific Advisory Board (REMICADELYM4001); Janssen: Other: Multiple Myeloma Registry Steering .

Risk of Non-Hodgkin's Lymphoma in HCV Patients in the United States Between 2013 and 2020: A Population-Based Study

Hepatitis C virus (HCV) is a significant healthcare problem affecting ~1% of the United States population. Meta-analyses of epidemiological studies reported a strong association between non-Hodgkin's lymphoma (NHL) and HCV. Direct oncogenic properties of HCV proteins and chronic antigenic stimulation are possible etiologies. We explored if NHL's prevalence has changed since older HCV therapy based on interferon that shared antiviral and anti-lymphoma properties was replaced with interferon-free direct-acting antivirals (DAA). We reviewed data from a nationwide database (Explorys, IBM) that aggregates records from 26 health-care-systems. We identified patients with chronic hepatitis C infection between June 2013 and June 2020. The control group was gender, race, and age-matched HCV-negative population. Statistical analysis used the odds ratio (OR) with P value <.001 for significance. There were 940 cases of NHL of 129,970 patients in the HCV group versus 107,480 cases of NHL of 37,961,970 in the control cohort [OR 2.6, 95% confidence interval (CI) 2.4-2.7]. A positive association was present for chronic lymphocytic leukemia, follicular lymphoma, marginal zone lymphoma, lymphoplasmacytic lymphoma, diffuse large B-cell lymphoma, Burkitt's lymphoma, non-Hodgkin T-cell lymphoma, and primary cutaneous T-cell lymphoma. There were no differences in Mantle cell lymphoma. The increased risk of HCV-associated lymphoma was persistent across genders, Caucasians and African-Americans, and age groups. While the risk of NHL in the HCV-negative population was higher in Caucasians than African-Americans (OR 1.8, 95% CI 1.7-1.8), the risk of HCV-associated NHL was not different. Further prospective studies examining the risk of HCV-associated lymphoma following DAA are warranted.

Association between the IL-1A, IL-1B and IL-1R polymorphisms and lymphoma

We investigate the impact of IL-1A, IL-1B and IL-1R1 polymorphism on lymphoma. This study consisted of 155 Non-Hodgkin’s lymphoma (NHL) patients 55 Hodgkin’s lymphoma (HL) patients and 150 healthy individuals. PCR-RFLP method and ARMS PCR were used for genotyping of IL-1A rs3783553, IL-1B rs3917356, rs16944, IL-1R1 rs10490571 and IL-1A rs3783550 polymorphism. The results showed that the CC genotype of rs3783550 as well Ins/del of rs3783553 increased the risk of NHL. In contrast the AG genotype of rs3917356 and AG also AG + AA genotype of rs10490571 decreased the risk of NHL. The result revealed that the CC genotype of rs3783550 and AG genotype of rs3917356 increased risk of HL.

Intravascular Lymphoma in Patient With Celiac Disease With Multi Glandular Involvement

Case Presentation: The patient is a 60 year old male with a past medical history of celiac disease, paroxysmal Afib, iron deficiency, and CAD who presented with lightheadedness, dizziness, and fatigue. Notable workup revealed that the patient had Afib with RVR, a TSH of 0.189, Free t4 0.51an LDH of 2726, hemoglobin of 8.7, AST of 155, ALT of 19, WBC of 4.5, and serum iron of 20. The patient’s cardizem dose was adjusted and repeat transthoracic echocardiogram was unremarkable compared to history. The patient presented again with complaints of abdominal distension, postural dizziness, occasional night sweats, and fevers. Repeat workups revealed pancytopenia, proteinuria, hypotension, and anasarca most pronounced in the lower extremity and scrotum. Ultimately, a kidney biopsy revealed an intravascular B cell non-Hodgkin lymphoma (IVBCL). Notable repeat labs include a CRP of 44 and a failed ACTH stimulation test. A brain MRI revealed a 6mm pituitary microadenoma. The patient placed on an R-CHOP regiment and is scheduled for repeat MRI to rule out pituitary involvement. Discussion: IVBCL’s are a rare form of diffuse B cell lymphoma and remain a diagnostic challenge due to the variety of involved systems including skin, CNS, and endocrine. IVBCL is also known to not produce a mass or lymphadenopathy. Celiac disease is a known risk factor for non-Hodgkin’s lymphoma. A literature search reveals a few case reports with common themes of increased LDH and inflammatory markers, anemia, and hepatic and renal dysfunction. Postural hypotension can also be a presenting symptom due to IVBCL’s ability to infiltrate neurovascular tissue to cause autonomic neuropathy. However, in this case, the patient’s history of primary adrenal insufficiency makes this unlikely. Hypothyroidism secondary to pituitary and thyroid involvement was suspected due to TSH level suppressed enough for central hypothyroidism. Repeated MRI showed resolution of Pituitary Microadenoma post Chemo therapy.Sylvain Raoul Simeni Njonnou, Bruno Couturier, Yannick Gombeir, Sylvain Verbanck, France Devuyst, Georges El Hachem, Ivan Theate, Anne-Laure Trepant, Virginie De Wilde, Frédéric-Alain Vandergheynst, “Pituitary Gland and Neurological Involvement in a Case of Hemophagocytic Syndrome Revealing an Intravascular Large B-Cell Lymphoma”, Case Reports in Hematology, vol. 2019, 6 pages, 2019. https://doi.org/10.1155/2019/9625075Catassi C, Fabiani E, Corrao G, et al. Risk of Non-Hodgkin Lymphoma in Celiac Disease. JAMA. 2002;287(11):1413Khan MS, McCubbin M, Nand S. Intravascular Large B-Cell Lymphoma: A Difficult Diagnostic Challenge. J Investig Med High Impact Case Rep. 2014 Mar 6;2(1):2324709614526702.Pearce C, Hope S, Butchart J. Intravascular lymphoma presenting with postural hypotension. BMJ Case Rep.Published 2018 Jan 29.

Diffuse large B-cell lymphoma in the liver accompanied by primary biliary cholangitis: A rare and difficult-to-diagnose tumor with portal venous thrombosis.

Introduction and importanceThe most common liver malignancies are hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and metastatic tumors. Hepatocellular carcinoma and intrahepatic cholangiocarcinoma may invade the portal vein (PV). An association between diffuse large B-cell lymphoma (DLBCL) and primary biliary cholangitis (PBC) remains unclear. We herein report a thought-provoking case of a difficult-to-diagnose liver tumor with PV thrombosis in a PBC patient.Presentation of caseA 66-year-old woman had PBC, systemic sclerosis, diabetes, and osteoporosis. A solitary liver tumor accompanied by macrovascular thrombosis in the PV was detected incidentally. Based on dynamic imaging findings, we considered the tumor to be intrahepatic cholangiocarcinoma, and right lobectomy with lymphadenectomy was performed. Unexpectedly, pathological assessment made a definitive diagnosis of DLBCL that did not invade the vessels and bile duct. In fluorine-18-fluorodeoxyglucose positron emission tomography, abnormal accumulations were clearly observed in the breast tissue and peritracheal, parasternal, mediastinal, and pericardial lymph nodes. The patient achieved complete remission after systemic chemotherapy, and there has been no recurrence 3 years after surgery.Clinical discussionPrimary lymphoma in the liver is rare, and we did not consider our patient's tumor as primary liver lymphoma. Our case actually showed no tumor thrombosis in the PV. Although autoimmune disorders may increase the risk of non-Hodgkin's lymphoma, an association between DLBCL and PBC is still unclear, and we must remember that DLBCL may develop rarely in a PBC patient.ConclusionOur case report provides a timely reminder for clinicians and surgeons in the fields of hepatology and hematology.

A Review and Update with Perspective of Evidence that the Herbicide Glyphosate (Roundup) is a Cause of Non-Hodgkin Lymphoma

Glyphosate-based formulations (GBFs), such as Roundup, are the most heavily used herbicides in the world. In 2015, the International Agency for Research on Cancer (IARC) concluded that glyphosate and GBFs are probably carcinogenic to humans (group 2A), mainly for non-Hodgkin lymphoma (NHL). However, this finding has been controversial, and most pesticide regulatory agencies have not followed their lead. The purpose of this review was to examine the scientific literature linking exposure to glyphosate and GBFs to the development of NHL, with emphasis on new findings since publication of the IARC report. The epidemiologic studies provide ample evidence for an association between exposure to GBFs and an increased risk of NHL. Animal studies have shown that glyphosate is carcinogenic in rodents and causes NHL in mice. Mechanistic studies have demonstrated that glyphosate and GBFs are genotoxic to human lymphocytes, the normal cell of origin of NHL, both in vitro and in vivo. Genotoxic and other biological effects have also been shown in various animal and cell models with these agents even at low doses. A novel mechanism underlying the specificity of glyphosate for NHL, that is upregulation of the B-cell genome mutator enzyme activation-induced cytidine deaminase, has recently been demonstrated. These findings were evaluated holistically using the guidelines for evaluation of general causation set forth by Bradford Hill. This evaluation provides coherent and compelling evidence that glyphosate and GBFs are a cause of NHL in humans exposed to these agents. These findings should prompt new reviews by pesticide regulatory agencies around the world.

Fibroblast Growth Factor Receptor 4 Gly388Arg Gene Polymorphism and Non-Hodgkin Lymphoma Susceptibility and Prognosis in Egyptian population: Case–control Study

BACKGROUND: Angiogenesis is a multistep process having an essential role in the growth and progression of various tumors including hematolymphoid malignancies. Basic fibroblast growth factor (bFGF) is one of angiogenic growth factors which level is considered as prognostic factor in lymphoma and leukemia. It mediates its action by binding to high affinity cell surface receptors-fibroblast growth factor receptor 1–4 (FGFR4) with receptor kinase activity. Therefore, upregulation of BFGF-FGFR system may cause increased risk of non-Hodgkin lymphomas (NHLs). AIM: Our study aimed to determine the association between the FGFR4 Gly388Arg (rs351855G/A) polymorphism and NHL disease susceptibility and prognosis. MATERIALS AND METHODS: The present study included 75 NHL patients and 100 healthy controls. Genotyping of FGFR4 was done by Polymerase Chain Reaction-Restriction Fragment Length polymorphism (PCR-RFLP). As after the amplification of the target gene, the PCR products were digested with BstNI restriction endonuclease enzyme. RESULTS: Analysis of FGFR4 Gly388Arg polymorphism revealed that the frequency of heterozygous (GA) mutation as well as the mutant allele (A) was significantly higher in cases compared to control subjects with p &lt; 0.001 and 0.002, respectively. The mutant genotypes were more prevalent at older age, aggressive clinical stage, bone marrow involvement, anemia, and thrombocytopenia at presentation. The mean of overall survival and the event free survival of our NHL patients were shorter in the mutant genotypes with p = 0.049 and 0.017, respectively. CONCLUSION: This study provides evidence that FGFR4 Gly388Arg polymorphism confers a genetic susceptibility to NHL among Egyptians and has a poor prognostic impact.

Residential Proximity to Dioxin-emitting Facilities and Risk of Non-Hodgkin Lymphoma in the NIH-AARP Diet and Health Study

Abstract Purpose: Few studies have investigated the relationship between risk of non-Hodgkin lymphoma (NHL) and residential proximity to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) emitted from industrial combustion and manufacturing sources. Methods: We evaluated this relationship among participants of the NIH-AARP Diet and Health Study, a prospective cohort (N = 548,845) in 6 states and 2 cities in the U.S. We linked geocoded enrollment addresses (1995–1996) with a U.S. Environmental Protection Agency database of 4,478 historical PCDD/F sources, which contained toxic equivalency quotient (TEQ) emissions estimates from 1995. Exposure metrics indicated presence/absence of any facility within 3 and 5km of participant homes, overall and by type of facility (e.g., coal-fired power plants, waste incinerators), which vary in emissions levels and constituency. We also calculated exposure as a distance- and toxicity-weighted average emissions index (AEI [g TEQ]). We used Cox regression to estimate associations (hazard ratios; HR and 95% confidence intervals; CI) with NHL and major subtypes, adjusting for and by strata of sociodemographic and lifestyle characteristics. Results: With 6,747 incident cases through 2011, we found no association between living near any or specific types of PCDD/F-emitting facilities and NHL risk. However, participants with an AEI &amp;gt;95th percentile within 5km had increased risk of NHL compared to unexposed (HR = 1.28; CI = 1.05–1.55; p-trend = 0.01). Specifically, we observed increased risk for lymphoplasmacytic lymphoma (HR = 2.98, CI = 1.16–7.63; p-trend = 0.03) and diffuse large B-cell lymphoma (HR = 1.65, CI = 1.11–2.46; p-trend = 0.01). Non-Hispanic blacks were nearly three times as likely as whites to live &amp;lt;5 km of a facility, although we had limited power to evaluate heterogeneity in associations by race/ethnicity. Associations did not vary by age, smoking status, body mass index, or urbanicity of residence. Conclusions: Using an exposure metric accounting for distance and the toxicity of emissions, we found significant positive associations between residential exposure to high PCDD/F emissions and risk of NHL and two subtypes. Our results underscore the hazard for populations living near sources of these persistent organic pollutants.

Association between the Interleukin-1 Receptor Antagonist (IL1RN) Variable Number of Tandem Repeats (VNTR) Polymorphism and Lymphoma.

Introduction: Lymphoma is a common hematopoietic cancer. Immunosuppression is one of the main risk factors for the development of lymphoma. The interleukin (IL)-1 receptor antagonist IL1RN, which binds to the IL-1 receptor, moderates a variety of immune responses related to IL-1. We aimed to assess the impact of IL1RN variable number of tandem repeats (VNTR) polymorphism on lymphoma risk in an Iranian population sample. Materials and Methods: DNA was extracted from peripheral blood of 120 subjects with non-Hodgkin Lymphoma (NHL), 50 subjects with Hodgkin’s lymphoma (HL), and 186 unrelated healthy individuals. IL1RN VNTR polymorphism was detected using polymerase chain reaction. Results: Our findings revealed that the IL1RN VNTR polymorphism was associated with protection against NHL (P≤0.001, OR: 0.30, 95% CI: 0.18-0.53). The IL1RN 2 allele significantly decreased the risk of NHL (p = 0.023, OR = 0.66, 95%CI = 0.46–0.93). In addition, we found that IL1RN 1/2 was associated with a lower risk of HL (p ≤0.001, OR = 0.24, 95%CI = 0.12–0.50). Conclusion: Our results suggest that the presence of IL1RN VNTR polymorphism is associated with a decreased risk of lymphoma in an Iranian subpopulation in southeast Iran.

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

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

Aspirin and other nonsteroidal anti-inflammatory drugs, statins and risk of non-Hodgkin lymphoma.

Non-steroidal anti-inflammatory drugs (NSAIDs) and statin drugs may protect against the development of non-Hodgkin lymphoma (NHL), but data are limited, particularly for NHL subtypes. Furthermore, some in vitro, animal and epidemiologic data suggest there may be a synergistic effect of these two agents, but there has been no test of this hypothesis in NHL. We evaluated the self-reported use of NSAIDs and statins in a clinic-based study of 1703 NHL patients and 2199 frequency-matched controls. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for potential confounding variables. We observed an inverse association of regular use of low-dose aspirin with risk of NHL (OR = 0.82; 95% CI 0.70-0.96) that was stronger with longer duration of use (P < .01). There were no associations for use of regular or extra-strength aspirin, ibuprofen, other NSAIDs, statins or other cholesterol-lowering drugs with NHL risk, while an inverse association with COX-2 inhibitors was equivocal. There was also no interaction of low-dose aspirin and statins on NHL risk. Inverse associations of similar magnitude to all NHL were observed for regular use of low-dose aspirin with diffuse large B-cell, follicular, marginal zone and all other lymphomas, although not all associations were statistically significant. In conclusion, low-dose aspirin but not regular/extra strength aspirin, other NSAIDs or statin use was associated with lower risk of NHL. Beyond the potential for the primary prevention of NHL, these data also point to a role of anti-platelet or other effects of low-dose aspirin in lymphomagenesis that warrant follow-up.

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.

Cancer incidence and factors associated with malignancies in coeliac disease during long‐term follow‐up

Background The increased risk of malignancies in coeliac disease is well recognised, but data on incidence and predisposing factors are scarce. Our aim was to determine cancer incidence and its prognostic factors in coeliac disease during a long-term follow-up. Methods The study cohort comprised all (n = 1460) coeliac patients diagnosed in Tampere University Hospital catchment area during the period 1960-2000. Demographic data (age, gender, decade of diagnosis) and coeliac disease characteristics (presenting symptoms, signs of malabsorption, severity of villous atrophy) were obtained from medical records, and patients were stratified into subgroups accordingly. Standardised incidence ratios (SIRs) compared to general population of the same area were calculated for malignancies altogether and according to stratifications. Results The overall risk of malignancy was not increased (SIR 0.97; 95% confidence interval (CI) 0.84-1.11). The risk of non-Hodgkin lymphoma was elevated (SIR 3.0; 1.88-4.54) but less so after ≥15 years of follow-up (SIR 1.75; 0.70-3.60). Screen-detected coeliac disease or malabsorption at diagnosis was not associated with increased risk of non-Hodgkin lymphoma. The increased risk of gastrointestinal malignancies (SIR 1.42; 95% CI 1.07-1.85), particularly that of stomach and liver cancers, was associated with females, coeliac disease diagnosis before year 1981 and dermatitis herpetiformis. Conclusions The overall risk of malignancy was not increased in any coeliac disease phenotype. The risk of non-Hodgkin lymphoma was increased but not in screen-detected coeliac disease.

Sunlight exposure in association with risk of lymphoid malignancy: a meta-analysis of observational studies

Several observational studies have shown contradictory results regarding the association between sunlight exposure and the risk of malignant lymphoma. Thus, we aimed to systematically determine the association between sunlight exposure and lymphoid malignancy risk through a meta-analysis. A thorough search of four electronic databases (PubMed, Embase, Web of Science, and Scopus) was performed to identify eligible studies until 13 August 2020. A random-effects model was used to calculate risk estimates of sunlight exposure. The main outcome measure was the risk of lymphoid malignancy subtypes with odds ratios (ORs) and 95% confidence intervals (CIs) according to various forms of solar ultraviolet radiation. In total, 17 case-control studies and 9 cohort studies including 216,285 non-Hodgkin lymphoma (NHL) and 23,017 Hodgkin's lymphoma (HL) patients were included in the final analysis. Personal sunlight exposure was significantly associated with a decreased risk of HL (OR 0.77; 95% CI 0.68-0.87) and NHL (OR 0.81; 95% CI 0.71-0.92), including all subtypes except T-cell lymphoma. Ambient sunlight exposure at residence was associated with a reduced risk of HL (OR 0.88; 95% CI 0.81-0.95) and all NHL subtypes (OR 0.84; 95% CI 0.73-0.96), except for chronic lymphocytic leukemia/small lymphocytic lymphoma. As the number of sunburns and sunbaths increased, the risk of NHL tended to decrease. While there was an observed protective effect both from case-control and prospective studies, substantial heterogeneity was found in the current study. Thus, more evidence is required to confirm that promoting sunlight exposure can prevent the development of lymphoid neoplasia.

Increased cancer risk in patients with cutaneous lupus erythematosus and systemic lupus erythematosus compared with the general population: A Danish nationwide cohort study.

To investigate if patients with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) have an increased risk of cancer compared with the general population, and furthermore to identify specific cancer types associated with increased risk. This is an observational cohort study of 5310 patients with CLE or SLE identified in the Danish National Patient Register from 1 January 1995 to 31 December 2014. The cohort was followed up for cancer by linkage to the Danish Cancer Registry. Based on the age, sex, and calendar specific cancer rates of the general population of Denmark, standardised incidence ratios (SIRs) were calculated. The patients with CLE or SLE were followed for 40.724 person-years, each group's average duration of follow-up being 6.9 and 8.1 years. The SIR for overall cancer (except non-melanoma skin cancer (NMSC)) was increased in patients with CLE 1.35 (95%CI 1.15 to 1.58) and patients with SLE 1.45 (95%CI 1.30 to 1.62). Both groups had high risks of hematological - including a 3-4-fold increased risk of non-Hodgkin lymphoma -, pancreatic, and lung cancers. Several cancers associated with oncogenic viruses as liver and tongue/mouth/pharynx were increased in the SLE group, while the risk of ovarian cancer was increased 2-4-fold only in the CLE group. The overall risk of cancer was significantly increased in both patients with CLE and SLE. SIRs for hematological, pancreatic and lung cancers were elevated in both groups. Extra awareness of cancer in patients with SLE and patients with CLE should be considered.

On recent meta-analyses of exposure to glyphosate and risk of non-Hodgkin's lymphoma in humans.

A recent meta-analysis of five case-control studies and one cohort study reported that exposure to glyphosate was associated with increased risk of non-Hodgkin's lymphoma (NHL). The meta-analysis was based on estimates of risk from the included studies at the highest reported exposure level obtained from analyses with the longest lag period. The extent to which the summary estimate depends upon the exposure definitions and assumed latency period is uncertain. We carried out sensitivity analyses to determine how the definition of exposure and the choice of latency period affect the summary estimate from meta-analyses of the 6 studies included in the recent meta-analysis. We also conducted a meta-analysis of ever-exposure to glyphosate incorporating the most updated results from the case-control studies. The summary estimates of risk varied considerably depending on both the assumptions about exposure level and latency. Using the highest reported exposure levels, evidence of an association between glyphosate and NHL was strongest when estimates from analyses in the cohort study with a 20-year lag [RR = 1.41 (95% CI 1.13-1.76)] and a 15-year lag [RR = 1.25 (95% CI 1.01-1.25)] were included. In our meta-analysis of ever-exposure with no lag period, the summary relative risk with updated estimates was 1.05 (95% CI 0.87-1.28). The results of meta-analyses of glyphosate exposure and NHL risk depend on assumptions made about both exposure level and latency period. Our results for ever-exposure are consistent with those of two recent meta-analyses conducted using somewhat different study inclusion criteria.