Genetic Variation in B-Cell–Activating Factor Is Associated with an Increased Risk of Developing B-Cell Non–Hodgkin Lymphoma

Abstract We conducted a population-based, case-control study in Connecticut women to test the hypothesis that genetic variations in Th1 and Th2 cytokine genes modify the relationship between body mass index (BMI) and risk of non-Hodgkin lymphoma (NHL). Compared with those with BMI less than 25 kg/m2, women with BMI more than or equal to 25 kg/m2 had 50% to 90% increased risk of NHL among women who carried IFNGR2 (rs9808753) AA, IL5 (rs2069812) CT/TT, IL7R (rs1494555) AA, and TNF (rs1799724) CC genotypes, but no increased risk among women with IFNGR2 AG/GG, IL5 CC, IL7R AG/GG, and TNF CT/TT genotypes. A significant interaction with BMI was only observed for IFNGR2 (rs9808753 Pforinteraction = .034) and IL7R (rs1494555 Pforinteraction = .016) for NHL overall; IL7R (rs1494555 Pforinteraction = .016) and TNF (1799724 Pforinteraction = .031) for B-cell lymphoma; and IL5 (rs2069812 Pforinteraction = .034) for T-cell lymphoma. After stratification by common B-cell lymphoma subtypes, a significant interaction was observed for IFNGR2 (rs9808753 Pforinteraction = .006), IL13 (rs20541 Pforinteraction = .019), and IL7R (rs1494555 Pforinteraction = .012) for marginal zone B-cell lymphoma; IL7R (rs1494555 Pforinteraction = .017) for small lymphocytic lymphoma/chronic lymphocytic leukemia; and IL12A (rs568408 Pforinteraction = .013) and TNF (1799724 Pforinteraction = .04) for follicular lymphoma. The results suggest that common genetic variation in Th1/Th2 pathway genes may modify the association between BMI and NHL risk.

Download Full-text

Late Health Outcomes After Contemporary Lymphome Malin de Burkitt Therapy for Mature B-Cell Non-Hodgkin Lymphoma: A Report From the Childhood Cancer Survivor Study

Journal of Clinical Oncology ◽

10.1200/jco.19.00525 ◽

2019 ◽

Vol 37 (28) ◽

pp. 2556-2570 ◽

Cited By ~ 2

Author(s):

Matthew J. Ehrhardt ◽

Yan Chen ◽

John T. Sandlund ◽

Elizabeth C. Bluhm ◽

Robert J. Hayashi ◽

...

Keyword(s):

Health Status ◽

Health Outcomes ◽

B Cell ◽

Hodgkin Lymphoma ◽

Chronic Health Conditions ◽

Health Conditions ◽

Socioeconomic Outcomes ◽

Non Hodgkin Lymphoma ◽

Increased Risk ◽

Childhood Cancer Survivor Study

PURPOSE The widely used, risk-based Lymphome Malin de Burkitt (LMB) chemotherapy regimen has improved survival rates for children with mature B-cell non-Hodgkin lymphoma (NHL); however, associated late effects remain understudied. We assessed late health outcomes after LMB treatment in the Childhood Cancer Survivor Study. PATIENTS AND METHODS Multivariable regression models compared chronic health conditions, health status, and socioeconomic and neurocognitive outcomes between survivors of NHL treated with the LMB regimen (n = 126), survivors of NHL treated with non-LMB regimens (n = 444), and siblings (n = 1,029). RESULTS LMB survivors were a median age of 10.2 years (range, 2.5 to 20.5 years) at diagnosis and 24.0 years (range, 10.3 to 35.3 years) at evaluation. Compared with siblings, LMB survivors were at increased risk for adverse health outcomes. However, survivors of NHL treated with LMB and non-LMB regimens did not differ with regard to risk of having any chronic health conditions, impaired health status, neurocognitive deficits, or poorer socioeconomic outcomes. Increased risk for the following specific neurologic conditions was observed in LMB survivors compared with non-LMB survivors: epilepsy (relative risk [RR], 15.2; 95% CI, 3.1 to 73.4); balance problems (RR, 8.9; 95% CI, 2.3 to 34.8); tremors (RR, 7.5; 95% CI, 1.9 to 29.9); weakness in legs (RR, 8.1; 95% CI, 2.5 to 26.4); severe headaches (RR, 3.2; 95% CI, 1.6 to 6.3); and prolonged arm, leg, or back pain (RR, 4.0; 95% CI, 2.2 to 7.1). The survivors from the group C LMB risk group (n = 50) were at the highest risk for these conditions; however, except for worse functional status (odds ratio, 2.7; 95% CI, 1.2 to 5.8), they were not at increased risk for other adverse health status or socioeconomic outcomes compared with non-LMB survivors. CONCLUSION Survivors treated with LMB and non-LMB regimens are largely comparable in late health outcomes except for excess neurotoxicity among LMB survivors. These data inform treatment efforts seeking to optimize disease control while minimizing toxicity.

Download Full-text

B-cell non-Hodgkin lymphoma linked to Coxiella burnetii

Blood ◽

10.1182/blood-2015-04-639617 ◽

2016 ◽

Vol 127 (1) ◽

pp. 113-121 ◽

Cited By ~ 44

Author(s):

Cléa Melenotte ◽

Matthieu Million ◽

Gilles Audoly ◽

Audrey Gorse ◽

Hervé Dutronc ◽

...

Keyword(s):

Tumor Microenvironment ◽

B Cell ◽

Hodgkin Lymphoma ◽

Coxiella Burnetii ◽

Q Fever ◽

Non Hodgkin Lymphoma ◽

Increased Risk ◽

Key Points

Key PointsCoxiella burnetii is associated with an increased risk of lymphoma; its presence in the tumor microenvironment may favor lymphomagenesis. Lymphoma has to be considered in patients with Q fever and lymphoid disorders, especially those with persistent focalized infections.

Download Full-text

The Correlation Between Non-Hodgkin Lymphoma and Expression Levels of B-Cell Activating Factor and Its Receptors

Advances in Clinical and Experimental Medicine ◽

10.17219/acem/29182 ◽

2016 ◽

Vol 25 (5) ◽

pp. 837-844 ◽

Cited By ~ 5

Author(s):

xianjuan shen ◽

mei wang ◽

yuehua guo ◽

shaoqing ju

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Expression Levels ◽

Non Hodgkin Lymphoma ◽

B Cell Activating Factor

Download Full-text

Hepatitis B Infection Is Associated with an Increased Risk of Non-Hodgkin Lymphoma: A Meta-Analysis.

Blood ◽

10.1182/blood.v120.21.2658.2658 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2658-2658

Author(s):

Samir Dalia ◽

Julio Chavez ◽

Jorge J Castillo ◽

Lubomir Sokol

Keyword(s):

Hepatitis B ◽

B Cell ◽

Hodgkin Lymphoma ◽

Cell Lymphoma ◽

Meta Analysis ◽

B Cell Lymphoma ◽

Lymphocytic Leukemia ◽

Hbv Infection ◽

Non Hodgkin Lymphoma ◽

Increased Risk

Abstract Abstract 2658 Introduction: Hepatitis B virus (HBV) infection is a major global public health problem with the World Health Organization reporting about 350 million people with chronic HBV infection with the highest rates seen in Asia and Africa. Multiple studies have attempted to show an association between HBV infection and non-Hodgkin lymphoma (NHL) but have had conflicting results. Objectives: The primary aim of our study was to evaluate the association between HBV infection and the incidence of NHL using a meta-analysis of epidemiological studies. Secondary aims were to evaluate such association in NHL subtypes and by geographical region. Methods: A MEDLINE and Google Scholar search through July 2012 were undertaken using (Hepatitis B or hepatitis) AND (lymphoma OR “risk of lymphoma” OR “hematologic malignancies” OR “lymphoproliferative disorders” OR “non Hodgkin lymphoma”). Only epidemiological studies reporting on HBV infection and NHL were included. Hepatitis B status confirmation method was recorded. Meta-analyses were performed for NHL in general, by NHL subtypes, and according to geographical region. The outcome was calculated as odds ratio (OR). The random effects model (REM) was used to calculate the outcome. Heterogeneity was assessed by the I2 statistic. Publication bias was assessed by the trim-and-fill analysis. Literature search and data gathering were performed independently by at least 2 of the investigators. All graphs and calculations were obtained using Comprehensive Meta-Analysis version 2 (Biostat, Englewood, NJ). Results: Our search yielded 21 studies; 17 case-control studies accounted for 38,630 cases and 1,659,449 controls, and 4 prospective cohort studies accounted for 1,258 cases indentified in a cohort of over 2.4 million individuals. HBV infection was confirmed by seropositivity in 81% of studies (n=17). HBV infection patients had an OR 2.30 (95% CI 1.87–2.84; p=<0.001) of developing NHL. OR was significant in patients from Asian countries (OR 2.31, 95% CI 1.87–2.86, p<0.001) and in patients from American/European/Australian countries (OR 2.58, 95% CI 1.43–4.62, p=0.002). In subgroup analysis, HBV infection patients had an OR 2.10 (95% CI 1.27–3.49, p=0.004) of developing diffuse large B-cell lymphoma (DLBCL). In patients from Asian countries, HBV infection was associated with an increased risk of DLBCL (OR 3.05, 95% CI 1.86–5.00, p<0.001); an association was not found in patients from Europe or Australian studies. Patients with HBV infection had increased risk to develop follicular lymphoma (OR 1.966, 95% CI 1.211–3.193, p<0.001) and B-cell lymphomas (OR 2.67, 95% CI 2.08–3.43, p<0.001). Patients with HBV infection did not have increased risk to develop chronic lymphocytic leukemia/small cell lymphoma (OR 1.58, 95% CI 0.70–3.62, p=0.27) or T-cell lymphomas (OR 1.37, 95% CI 0.95–1.98, p=0.091). Conclusions: The results of this meta-analysis suggest a positive association between HBV infection and NHL, DLBCL, follicular lymphoma, and B-cell lymphoma. There was no association between HBV infection and chronic lymphocytic leukemia/small cell lymphoma or T-cell lymphomas. Future research is needed to better understand molecular mechanisms responsible for lymphomagenesis in patients with chronic HBV infection. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

A prospective study of serum soluble CD30 concentration and risk of non-Hodgkin lymphoma

Blood ◽

10.1182/blood-2009-04-217521 ◽

2009 ◽

Vol 114 (13) ◽

pp. 2730-2732 ◽

Cited By ~ 42

Author(s):

Mark P. Purdue ◽

Qing Lan ◽

Otoniel Martinez-Maza ◽

Martin M. Oken ◽

William Hocking ◽

...

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Ovarian Cancer Screening ◽

Hiv Patients ◽

Cell Stimulation ◽

Non Hodgkin Lymphoma ◽

Soluble Cd30 ◽

Increased Risk ◽

A Prospective Study ◽

Nested Case Control

Abstract Prediagnostic serum concentration of soluble CD30 (sCD30), a marker for chronic B-cell stimulation, has been associated with increased risk of developing AIDS-related non-Hodgkin lymphoma (NHL) in a recent study of HIV+ patients. To investigate among healthy persons whether serum sCD30 is associated with NHL risk, we carried out a nested case-control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. There was a strong dose-response relationship between prediagnostic sCD30 concentration and NHL risk among 234 cases and 234 individually matched controls (odds ratio [95% confidence interval] for second, third, and fourth quartiles vs first quartile: 1.4 [0.8-2.6], 2.2 [1.2-4.1], 4.1 [2.2-7.8]; Ptrend < .001), which persisted among cases diagnosed 6 to 10 years after providing a blood sample. Given that a similar relationship has been observed among HIV+ patients, our findings suggest that chronic B-cell stimulation may be an important mechanism involved in B-cell lymphomagenesis among severely immunocompromised and healthy populations alike.

Download Full-text

Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium

Blood ◽

10.1182/blood-2007-10-119974 ◽

2008 ◽

Vol 111 (8) ◽

pp. 4029-4038 ◽

Cited By ~ 350

Author(s):

Karin Ekström Smedby ◽

Claire M. Vajdic ◽

Michael Falster ◽

Eric A. Engels ◽

Otoniel Martínez-Maza ◽

...

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Fixed Effects ◽

Large Scale ◽

Marginal Zone ◽

Pooled Analysis ◽

Autoimmune Disorders ◽

Non Hodgkin Lymphoma ◽

Increased Risk ◽

Large B Cell

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

Download Full-text

Determination of the binding affinity of RNA aptamer to B‐cell activating factor receptor protein from non‐Hodgkin lymphoma

The FASEB Journal ◽

10.1096/fasebj.2019.33.1_supplement.460.1 ◽

2019 ◽

Vol 33 (S1) ◽

Author(s):

Thanh Phan Blade ◽

Stephanie Roa ◽

Tara Avrit

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Binding Affinity ◽

Receptor Protein ◽

Rna Aptamer ◽

Non Hodgkin Lymphoma ◽

B Cell Activating Factor

Download Full-text

PRRC2A and BCL2L11 gene variants influence risk of non-Hodgkin lymphoma: results from the InterLymph consortium

Blood ◽

10.1182/blood-2012-05-427989 ◽

2012 ◽

Vol 120 (23) ◽

pp. 4645-4648 ◽

Cited By ~ 19

Author(s):

Alexandra Nieters ◽

Lucia Conde ◽

Susan L. Slager ◽

Angela Brooks-Wilson ◽

Lindsay Morton ◽

...

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Odds Ratio ◽

B Cell Lymphoma ◽

Class Iii ◽

Case Control Studies ◽

Non Hodgkin Lymphoma ◽

Common Genetic Variants ◽

Increased Risk ◽

Study Results

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

Download Full-text