scholarly journals Oncogenic Effects of HIV-1 Proteins, Mechanisms Behind

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 305
Author(s):  
Maria Isaguliants ◽  
Ekaterina Bayurova ◽  
Darya Avdoshina ◽  
Alla Kondrashova ◽  
Francesca Chiodi ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Viral Infections ◽  
Kaposi Sarcoma ◽  
Successful Implementation ◽  
Non Hodgkin Lymphoma ◽  
Increased Risk ◽  
Carcinogenic Effects ◽  
Infected Cells ◽  
Transactivator Of Transcription ◽  
Hiv 1

People living with human immunodeficiency virus (HIV-1) are at increased risk of developing cancer, such as Kaposi sarcoma (KS), non-Hodgkin lymphoma (NHL), cervical cancer, and other cancers associated with chronic viral infections. Traditionally, this is linked to HIV-1-induced immune suppression with depletion of CD4+ T-helper cells, exhaustion of lymphopoiesis and lymphocyte dysfunction. However, the long-term successful implementation of antiretroviral therapy (ART) with an early start did not preclude the oncological complications, implying that HIV-1 and its antigens are directly involved in carcinogenesis and may exert their effects on the background of restored immune system even when present at extremely low levels. Experimental data indicate that HIV-1 virions and single viral antigens can enter a wide variety of cells, including epithelial. This review is focused on the effects of five viral proteins: envelope protein gp120, accessory protein negative factor Nef, matrix protein p17, transactivator of transcription Tat and reverse transcriptase RT. Gp120, Nef, p17, Tat, and RT cause oxidative stress, can be released from HIV-1-infected cells and are oncogenic. All five are in a position to affect “innocent” bystander cells, specifically, to cause the propagation of (pre)existing malignant and malignant transformation of normal epithelial cells, giving grounds to the direct carcinogenic effects of HIV-1.

scholarly journals HIV-1 Reverse Transcriptase Promotes Tumor Growth and Metastasis Formation via ROS-Dependent Upregulation of Twist

2019 ◽  
Vol 2019 ◽  
pp. 1-28 ◽  
Author(s):  
Ekaterina Bayurova ◽  
Juris Jansons ◽  
Dace Skrastina ◽  
Olga Smirnova ◽  
Dzeina Mezale ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Reverse Transcriptase ◽  
Immune Suppression ◽  
Viral Infections ◽  
Kaposi Sarcoma ◽  
Rnase H ◽  
Infected People ◽  
Increased Risk ◽  
Hiv 1

HIV-induced immune suppression results in the high prevalence of HIV/AIDS-associated malignancies including Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer. HIV-infected people are also at an increased risk of “non-AIDS-defining” malignancies not directly linked to immune suppression but associated with viral infections. Their incidence is increasing despite successful antiretroviral therapy. The mechanism behind this phenomenon remains unclear. Here, we obtained daughter clones of murine mammary gland adenocarcinoma 4T1luc2 cells expressing consensus reverse transcriptase of HIV-1 subtype A FSU_A strain (RT_A) with and without primary mutations of drug resistance. In in vitro tests, mutations of resistance to nucleoside inhibitors K65R/M184V reduced the polymerase, and to nonnucleoside inhibitors K103N/G190S, the RNase H activities of RT_A. Expression of these RT_A variants in 4T1luc2 cells led to increased production of the reactive oxygen species (ROS), lipid peroxidation, enhanced cell motility in the wound healing assay, and upregulation of expression of Vimentin and Twist. These properties, particularly, the expression of Twist, correlated with the levels of expression RT_A and/or the production of ROS. When implanted into syngeneic BALB/C mice, 4T1luc2 cells expressing nonmutated RT_A demonstrated enhanced rate of tumor growth and increased metastatic activity, dependent on the level of expression of RT_A and Twist. No enhancement was observed for the clones expressing mutated RT_A variants. Plausible mechanisms are discussed involving differential interactions of mutated and nonmutated RTs with its cellular partners involved in the regulation of ROS. This study establishes links between the expression of HIV-1 RT, production of ROS, induction of EMT, and enhanced propagation of RT-expressing tumor cells. Such scenario can be proposed as one of the mechanisms of HIV-induced/enhanced carcinogenesis not associated with immune suppression.

The Prevalence of HIV-1 DNA in AIDS-Related Lymphoma throughout the Epidemic in the US

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5205-5205
Author(s):  
Leanne C Huysentruyt ◽  
Lawrence D Kaplan ◽  
Michael S. McGrath
Keyword(s):  
Highly Active Antiretroviral Therapy ◽  
Conflicts Of Interest ◽  
Kaposi Sarcoma ◽  
Sequence Evolution ◽  
Genomic Amplification ◽  
Hiv Dna ◽  
Non Hodgkin Lymphoma ◽  
Highly Active ◽  
Reported Data ◽  
Hiv 1

Abstract Abstract 5205 Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL) are the two most common AIDS-defining cancers and significantly contribute to HIV-related deaths. While highly active antiretroviral therapy (HAART) has produce a sharp decline in the incidence of KS and AIDS-related NHL (ARL), HIV-infected patients are still at a high risk for developing these malignancies. Recent studies evaluating HIV-1 DNA in 91 AIDS-related KS cases demonstrated a significant decrease in the prevalence of HIV-1 DNA positive KS cases post-HAART (after 1996; 16.7%) as compared to pre-HAART (before 1996; 45%) corresponding to the decrease in incidence of this cancer since the introduction of HAART. Additionally HIV was more prevalent in sites of visceral KS (51.9%) as compared to skin KS (30.7%). We have recently evaluated the HIV sequence evolution in the context of metastatic ARL and identified lymphoma-specific HIV compartmentalized within tumor sites that was genetically distinct from HIV in non-tumor sites suggesting a specific form of HIV arises within individuals who develop ARL. The goal of this research was to determine the prevalence and quantity of HIV DNA in 119 ARL biopsies representing the entire span of the HIV epidemic (1982–2005). Whole genomic amplification was performed on DNA extracted from three 10um paraffin embedded tissue sections and the presence of HIV-1 DNA was determined by quantitative amplification of the HIV gag gene. Of the 119 cases, 45% contained detectable levels of HIV DNA. The HIV antigen was predominantly localized to macrophages. A subset of the ARL cases in this study contained approximately 1 HIV copy per cell which is extremely high considering previously reported data describing HIV-infected lymph nodes contained approximately 1 HIV copy per 1000 cells. Similar to what was observed for KS, the prevalence of HIV-positive ARLs has decreased in the post-HAART era (39%) when compared to pre-HAART (54%). While the prevalence of HIV-1 DNA positive ARLs declined in the post-HAART era, it was not to the same extent as what was observed for KS. Thus, our data is consistent with a decrease in the incidence of both tumor types in the post-HAART era. The higher prevalence of HIV-1 DNA in visceral sites of KS and lymphoma specific-HIV sequences in sites of metastatic lymphoma suggests that HIV, especially HIV infected macrophages, may play a role in the pathogenesis of KS and ARL disease progression. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Autophagy Promotes Infectious Particle Production of Mopeia and Lassa Viruses

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 293 ◽  
Author(s):  
Nicolas Baillet ◽  
Sophie Krieger ◽  
Alexandra Journeaux ◽  
Valérie Caro ◽  
Frédéric Tangy ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Particle Production ◽  
Defense Mechanism ◽  
Viral Infections ◽  
Hybrid Approach ◽  
Hemorrhagic Fever ◽  
Lassa Virus ◽  
Infectious Particle ◽  
Cellular Defense ◽  
Infected Cells

Lassa virus (LASV) and Mopeia virus (MOPV) are two closely related Old-World mammarenaviruses. LASV causes severe hemorrhagic fever with high mortality in humans, whereas no case of MOPV infection has been reported. Comparing MOPV and LASV is a powerful strategy to unravel pathogenic mechanisms that occur during the course of pathogenic arenavirus infection. We used a yeast two-hybrid approach to identify cell partners of MOPV and LASV Z matrix protein in which two autophagy adaptors were identified, NDP52 and TAX1BP1. Autophagy has emerged as an important cellular defense mechanism against viral infections but its role during arenavirus infection has not been shown. Here, we demonstrate that autophagy is transiently induced by MOPV, but not LASV, in infected cells two days after infection. Impairment of the early steps of autophagy significantly decreased the production of MOPV and LASV infectious particles, whereas a blockade of the degradative steps impaired only MOPV infectious particle production. Our study provides insights into the role played by autophagy during MOPV and LASV infection and suggests that this process could partially explain their different pathogenicity.

scholarly journals Identification of Modulators of HIV-1 Proviral Transcription from a Library of FDA-Approved Pharmaceuticals

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1067
Author(s):  
Gavin C. Sampey ◽  
Sergey Iordanskiy ◽  
Michelle L. Pleet ◽  
Catherine DeMarino ◽  
Fabio Romerio ◽  
...  
Keyword(s):  
Viral Infections ◽  
High Morbidity ◽  
Immunodeficiency Virus ◽  
Transcriptional Modulators ◽  
The Usa ◽  
Infected Cells ◽  
Approved Drugs ◽  
Living With Hiv ◽  
Fda Approved Drugs ◽  
Hiv 1

Human immunodeficiency virus 1 (HIV-1) is the most prevalent human retrovirus. Recent data show that 34 million people are living with HIV-1 worldwide. HIV-1 infections can lead to AIDS which still causes nearly 20,000 deaths annually in the USA alone. As this retrovirus leads to high morbidity and mortality conditions, more effective therapeutic regimens must be developed to treat these viral infections. A key target for intervention for which there are no current FDA-approved modulators is at the point of proviral transcription. One successful method for identifying novel therapeutics for treating infectious diseases is the repurposing of pharmaceuticals that are approved by the FDA for alternate indications. Major benefits of using FDA-approved drugs include the fact that the compounds have well established toxicity profiles, approved manufacturing processes, and immediate commercial availability to the patients. Here, we demonstrate that pharmaceuticals previously approved for other indications can be utilized to either activate or inhibit HIV-1 proviral transcription. Specifically, we found febuxostat, eltrombopag, and resveratrol to be activators of HIV-1 transcription, while mycophenolate was our lead inhibitor of HIV-1 transcription. Additionally, we observed that the infected cells of lymphoid and myeloid lineage responded differently to our lead transcriptional modulators. Finally, we demonstrated that the use of a multi-dose regimen allowed for enhanced activation with our transcriptional activators.

Risk of secondary malignancies in non-Hodgkin lymphoma survivors: 40 years of follow-up assessed by treatment modality.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19525-e19525
Author(s):  
Matthew Parsons ◽  
Jonathan Chipman ◽  
Calvin Rock ◽  
Deborah Marie Stephens ◽  
Harsh Shah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Head And Neck ◽  
Treatment Modality ◽  
Kaposi Sarcoma ◽  
Female Breast Cancer ◽  
Secondary Malignancy ◽  
Non Hodgkin Lymphoma ◽  
Female Breast ◽  
Increased Risk

e19525 Background: Survivors of non-Hodgkin lymphoma (NHL) are at increased risk of secondary malignancies (SM). We quantified this risk in survivors with over 40 years of follow-up, and evaluated differences in risk by treatment modality. Methods: Standardized incidence ratios (SIR, observed-to-expected [O/E] ratio), which accounts for patient years at risk, and absolute excess risk of SM were assessed in 142,837 patients diagnosed with NHL as a first malignancy between 1975 and 2016 in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Follow up was available through 2016. Non-melanoma skin cancers were not counted as SM. SIRs were also evaluated for patients stratified by age at and latency from diagnosis. Results: In all, 14,101 patients received radiotherapy alone (RT), 68,424 received chemotherapy alone (CT), and 18,339 received chemotherapy and radiation (CRT). In total, 15,979 patients (11%) developed SM, more than the endemic rate (O/E 1.29; P < .01). Overall, patients treated with any RT (RT+CRT) had a similar risk of SM as those who did not receive RT (O/E 1.29 for both compared to endemic rate). Patients treated with RT had more risk of female breast cancer and less risk of leukemia than unirradiated patients (P < .05). Patients treated with any CT (CT+CRT) had increased SM rates compared with those who did not receive CT [O/E 1.33 (95% CI 1.30-1.35) vs 1.24 (95% CI 1.21-1.26), respectively], which included increased risks of leukemia, Kaposi sarcoma, kidney, pancreas, rectal, head and neck, and colon cancers and decreased risk of prostate cancer (P < 0.05). When stratified by four treatment groups (no CT or RT, RT alone, CT alone, CRT), there were no differences in SM rates between the no therapy and RT alone groups (O/E 1.24 95% CI 1.21-1.27 and O/E 1.23 95% CI 1.18-1.28 respectively). CT alone and CRT were associated with increased risk of secondary malignancy compared to the no therapy group (O/E 1.32 95% CI 1.29-1.35 and O/E 1.35 95% CI 1.29-1.40 respectively). CT alone was also associated with increased risk of leukemia, Kaposi sarcoma, kidney, head and neck and thyroid cancers, and a decreased risk of prostate cancer (P < .05). CRT was associated with increased risk of head and neck and female breast cancers (P < .05). There was no difference in the overall risk of SM between the CT alone and CRT groups and female breast cancer was the only site at which CRT was associated with higher risk than CT alone. Of note, female breast cancer risk was highest in those diagnosed under 25 years of age and at latencies of greater than 10 years. Conclusions: This is the largest study to examine secondary malignancy risk in patients with NHL and has the longest follow-up. Patients treated with RT alone did not have an increased SM risk compared to those who received no RT or CT. The risk of SMs was increased overall for NHL survivors and varied with treatment modality.

scholarly journals HIV-1 Persistence in Children during Suppressive ART

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1134
Author(s):  
Mary Grace Katusiime ◽  
Gert U. Van Zyl ◽  
Mark F. Cotton ◽  
Mary F. Kearney
Keyword(s):  
Antiretroviral Therapy ◽  
Early Life ◽  
Clonal Expansion ◽  
Hiv Cure ◽  
Major Barrier ◽  
Hiv Persistence ◽  
Increased Risk ◽  
Infected Cells ◽  
Hiv 1

There is a growing number of perinatally HIV-1-infected children worldwide who must maintain life-long ART. In early life, HIV-1 infection is established in an immunologically inexperienced environment in which maternal ART and immune dynamics during pregnancy play a role in reservoir establishment. Children that initiated early antiretroviral therapy (ART) and maintained long-term suppression of viremia have smaller and less diverse HIV reservoirs than adults, although their proviral landscape during ART is reported to be similar to that of adults. The ability of these early infected cells to persist long-term through clonal expansion poses a major barrier to finding a cure. Furthermore, the effects of life-long HIV persistence and ART are yet to be understood, but growing evidence suggests that these individuals are at an increased risk for developing non-AIDS-related comorbidities, which underscores the need for an HIV cure.

scholarly journals Role of HIV-1 matrix protein p17 variants in lymphoma pathogenesis

2015 ◽  
Vol 112 (46) ◽  
pp. 14331-14336 ◽  
Author(s):  
Riccardo Dolcetti ◽  
Cinzia Giagulli ◽  
Wangxiao He ◽  
Marina Selleri ◽  
Francesca Caccuri ◽  
...  
Keyword(s):  
Cell Growth ◽  
B Cell ◽  
Matrix Protein ◽  
Treatment Strategies ◽  
Independent Set ◽  
Akt Signaling ◽  
Insertion Mutant ◽  
Non Hodgkin Lymphoma ◽  
Growth Promoting ◽  
Hiv 1

Although in decline after successful anti-HIV therapy, B-cell lymphomas are still elevated in HIV-1-seropositive (HIV+) persons, and the mechanisms are obscure. The HIV-1 matrix protein p17 persists in germinal centers long after HIV-1 drug suppression, and some p17 variants (vp17s) activate Akt signaling and promote growth of transformed B cells. Here we show that vp17s derived from four of five non-Hodgkin lymphoma (NHL) tissues from HIV+ subjects display potent B-cell growth-promoting activity. They are characterized by amino acid insertions at position 117–118 (Ala–Ala) or 125–126 (Gly–Asn or Gly–Gln–Ala–Asn–Gln–Asn) among some other mutations throughout the sequence. Identical dominant vp17s are found in both tumor and plasma. Three of seven plasma samples from an independent set of NHL cases manifested multiple Ala insertions at position 117–118, and one with the Ala–Ala profile also promoted B-cell growth and activated Akt signaling. Ultradeep pyrosequencing showed that vp17s with C-terminal insertions are more frequently detected in plasma of HIV+ subjects with than without NHL. Insertion of Ala–Ala at position 117–118 into reference p17 (refp17) was sufficient to confer B-cell growth-promoting activity. In contrast, refp17 bearing the Gly–Asn insertion at position 125–126 did not, suggesting that mutations not restricted to the C terminus can also account for this activity. Biophysical analysis revealed that the Ala–Ala insertion mutant is destabilized compared with refp17, whereas the Gly–Asn form is stabilized. This finding provides an avenue for further exploration of structure function relationships and new treatment strategies in combating HIV-1–related NHL.

scholarly journals Expression of HIV-1 matrix protein p17 and association with B-cell lymphoma in HIV-1 transgenic mice

2016 ◽  
Vol 113 (46) ◽  
pp. 13168-13173 ◽  
Author(s):  
Virginia A. Carroll ◽  
Mark K. Lafferty ◽  
Luigi Marchionni ◽  
Joseph L. Bryant ◽  
Robert C. Gallo ◽  
...  
Keyword(s):  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Microarray Analysis ◽  
Intracellular Signaling ◽  
Matrix Protein ◽  
B Cell Lymphoma ◽  
Viral Proteins ◽  
Increased Risk ◽  
Hiv 1

HIV-1 infection is associated with increased risk for B-cell lymphomas. How HIV infection promotes the development of lymphoma is unclear, but it may involve chronic B-cell activation, inflammation, and/or impaired immunity, possibly leading to a loss of control of oncogenic viruses and reduced tumor immunosurveillance. We hypothesized that HIV structural proteins may contribute to lymphomagenesis directly, because they can persist long term in lymph nodes in the absence of viral replication. The HIV-1 transgenic mouse Tg26 carries a noninfectious HIV-1 provirus lacking part of the gag-pol region, thus constituting a model for studying the effects of viral products in pathogenesis. Approximately 15% of Tg26 mice spontaneously develop leukemia/lymphoma. We investigated which viral proteins are associated with the development of leukemia/lymphoma in the Tg26 mouse model, and performed microarray analysis on RNA from spleen and lymph nodes to identify potential mechanisms of lymphomagenesis. Of the viral proteins examined, only expression of HIV-1 matrix protein p17 was associated with leukemia/lymphoma development and was highly expressed in bone marrow before disease. The tumor cells resembled pro-B cells, and were CD19+IgM−IgD−CD93+CD43+CD21−CD23−VpreB+CXCR4+. Consistent with the pro-B-cell stage of B-cell development, microarray analysis revealed enrichment of transcripts, including Rag1, Rag2, CD93, Vpreb1, Vpreb3, and Igll1. We confirmed RAG1 expression in Tg26 tumors, and hypothesized that HIV-1 matrix protein p17 may directly induce RAG1 in B cells. Stimulation of human activated B cells with p17 enhanced RAG1 expression in three of seven donors, suggesting that intracellular signaling by p17 may lead to genomic instability and transformation.

scholarly journals Short Intracellular HIV-1 Transcripts as Biomarkers of Residual Immune Activation in Patients on Antiretroviral Therapy

2016 ◽  
Vol 90 (12) ◽  
pp. 5665-5676 ◽  
Author(s):  
Aya Ishizaka ◽  
Hidenori Sato ◽  
Hitomi Nakamura ◽  
Michiko Koga ◽  
Tadashi Kikuchi ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Immune Activation ◽  
Viral Suppression ◽  
Immune Status ◽  
Viral Persistence ◽  
Chronic Immune Activation ◽  
Viral Reservoirs ◽  
Increased Risk ◽  
Infected Cells ◽  
Hiv 1

ABSTRACTHIV-1 patients continue to remain at an abnormal immune status despite prolonged combination antiretroviral therapy (cART), which results in an increased risk of non-AIDS-related diseases. Given the growing recognition of the importance of understanding and controlling the residual virus in patients, additional virological markers to monitor infected cells are required. However, viral replication in circulating cells is much poorer than that in lymph nodes, which results in the absence of markers to distinguish these cells from uninfected cells in the blood. In this study, we identified prematurely terminated short HIV-1 transcripts (STs) in peripheral blood mononuclear cells (PBMCs) as an efficient intracellular biomarker to monitor viral activation and immune status in patients with cART-mediated full viral suppression in plasma. STs were detected in PBMCs obtained from both treated and untreated patients. ST levels in untreated patients generally increased with disease progression and decreased after treatment initiation. However, some patients exhibited sustained high levels of ST and low CD4+cell counts despite full viral suppression by treatment. The levels of STs strongly reflected chronic immune activation defined by coexpression of HLA-DR and CD38 on CD8+T cells, rather than circulating proviral load. These observations represent evidence for a relationship between viral persistence and host immune activation, which in turn results in the suboptimal increase in CD4+cells despite suppressive antiretroviral therapy. This cell-based measurement of viral persistence contributes to an improved understanding of the dynamics of viral persistence in cART patients and will guide therapeutic approaches targeting viral reservoirs.IMPORTANCECombination antiretroviral therapy (cART) suppresses HIV-1 load to below the detectable limit in plasma. However, the virus persists, and patients remain at an abnormal immune status, which results in an increased risk of non-AIDS-related complications. To achieve a functional cure for HIV-1 infection, activities of viral reservoirs must be quantified and monitored. However, latently infected cells are difficult to be monitored. Here, we identified prematurely terminated short HIV-1 transcripts (STs) as an efficient biomarker for monitoring viral activation and immune status in patients with cART-mediated full viral suppression in plasma. This cell-based measurement of viral persistence will contribute to our understanding of the impact of residual virus on chronic immune activation in HIV-1 patients during cART.

Non-Hodgkin Lymphoma and Smoking: A Meta-Analysis of Case-Control Studies

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5292-5292 ◽  
Author(s):  
Cannon Milani ◽  
Sheila Pascual ◽  
Joanna Mitri ◽  
Jorge Castillo
Keyword(s):  
Viral Infections ◽  
Case Reports ◽  
English Literature ◽  
Meta Analysis ◽  
Case Control ◽  
Case Control Studies ◽  
Random Effects Models ◽  
Non Hodgkin Lymphoma ◽  
Increased Risk ◽  
The Relationship

Abstract Background: The incidence of non-Hodgkins lymphoma (NHL) has followed a sustained increasing pattern for the last few decades. Potential factors implicated in developing an increased risk for NHL include immunosuppression, bacterial, and viral infections. The pathological heterogeneity of NHL suggests multifactorial etiologies. Several reports around the world have linked lifestyle habits to the development of NHL, but thus far, the relationship between smoking and NHL has been largely inconclusive. Objective: To perform a meta-analysis of published case-control studies to clarify the potential relationship between smoking and the development of NHL. Methods: An English literature search was conducted using Pubmed of case-control studies investigating the relationship between smoking and development of NHL. Prospective studies, case reports, editorials and letters were not included. Data were gathered including the following variables: country of origin, source of cases and controls, number of female/male cases and controls, adjusted odds ratio (OR) with 95% confidence intervals (CI) for former and current smokers, divided by male/female when available, and adjustments. Effect measures were obtained trough fixed and random-effects models to assess for heterogeneity. Results: Eighteen case-control studies were included in the meta-analysis. A total of 22,226 cases and 30,792 controls were finally analyzed. Based on our meta-analysis, former smokers had an OR of 1.02 (95% CI, 0.92 – 1.12) when compared to never smokers; heterogeneity between studies was evident (p &lt; 0.001; I2 = 75.3%). Current smokers, on the other hand, had an OR of 1.06 (95% CI, 1.00 – 1.14); some degree of heterogeneity was observed (p = 0.04; I2 = 41.1%). Conclusions: Despite the limitations of this meta-analysis, current smokers seem to have small but statistically significant increase in the risk of developing NHL. Clinically speaking, smoking may be a non-negligible risk factor for developing NHL. Although a causal relationship will be hard to prove, further research is needed to clarify the potential role of smoking in lymphomagenesis.

Sign in / Sign up

Export Citation Format

Share Document