Risk Factor For non-Hodgkin Lymphoma Research Articles

Risk factors for Non-Hodgkin's lymphoma in autoimmune disease: a large database analysis.

Immune dysregulation in autoimmune diseases (ADs) is a risk factor for the development of Non-Hodgkin's lymphoma (NHL). However, the underlying mechanisms are not well understood. Hence, this retrospective study aims to describe the clinical and demographic factors that increase the risk of NHL development in patients with ADs. Our study utilised data from National Inpatient Sample (NIS) for the duration of 2016-2020 on all adult patients aged > 18 years who had NHL. We divided them into two cohorts: one with underlying ADs and one without underlying ADs. We then compared the adjusted odds ratios (aOR) of various risk factors. It was found that 0.9% of autoimmune cases had NHL, while 0.7% of non-autoimmune cases had NHL. Among those with autoimmune conditions, various factors influenced the presence of lymphoma, such as personal history of chemotherapy or radiation, family history of lymphoid malignancy, HIV infection, advanced age of 60-69 years, Asian and Pacific Islander ethnicity and viral hepatitis. The increased risk of NHL with autoimmune conditions is well established. Studies have also shown that these patients can overall have a poor prognosis from their NHL when compared to patients without autoimmune diseases. However, there is limited literature regarding the interplay of traditional NHL risk factors with underlying autoimmunity. Hence, our study sheds light on the lesser studied risk factors, such as patient characteristics and comorbidities.

Risk Factors for Non-Hodgkin's Lymphoma in Autoimmune Diseases: A Large Database Analysis

Introduction It has been well studied that immune dysregulation in autoimmune diseases is a risk factor for the development of Non-Hodgkin's lymphoma (NHL). However, the underlying mechanisms are not well understood. Although certain traditional risk factors like prolonged immunosuppression, infections, advanced age, family history, and history of organ transplantation are well described in NHL patients, there is limited literature regarding their interplay with autoimmune diseases. Hence, we conducted this retrospective study from the National inpatient sample database to describe the various clinical and demographic factors that increase the risk of NHL development in patients with autoimmune diseases. Methods Our study was conducted using the National Inpatient Sample, which is a large all-payer inpatient care database in the United States. We collected data from 2016-2020 on all adult patients aged > 18 years who had NHL. We divided them into two cohorts: one with underlying autoimmune diseases and one without underlying autoimmune conditions. We then compared the adjusted odds ratios (aOR) of various risk factors like age, race, gender, obesity, family history of lymphoproliferative diseases, personal history of chemotherapy or radiation, history of HIV, HTLV-1, Helicobacter pylori infection, Chlamydia infection, history of solid organ transplantation, and long-term steroid use among the two cohorts. Results Our data initially consisted of 148,755,036 patients ages ≥18 years, with 4,291,559 cases having autoimmune disorders like rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Systemic sclerosis, sarcoidosis, sjogren's syndrome, and celiac disease. We found that 0.9% of autoimmune cases had NHL, while 0.7% of non-autoimmune cases had NHL (aOR 1.272, 95% CI 1.258-1.285, p<0.01). Among those with autoimmune conditions, various factors also influenced the presence of lymphoma, such as personal history of chemotherapy or radiation (aOR 5.778, 95% CI 5.595- 5.9675, p <0.001), family history of lymphoid malignancy (aOR 5.316, 95% CI 4.666-6.058, p<0.001), HIV infection (aOR 1.944, 95% CI 1.674-2.257,p<0.001), advanced age of 60-69 years (aOR 1.051, 95% CI 1.025-1.078, p<0.001) , Asian and Pacific Islander ethnicity (aOR 1.596, 95%CI 1.496-1.703, p<0.001) and viral hepatitis (aOR 1.620, 95% CI 1.480-1.774, p<0.001) (Table 1). Conclusion The increased risk of non-Hodgkin Lymphoma (NHL) with autoimmune conditions like rheumatoid arthritis and SLE is well established. Studies have also shown that these patients can overall have a poor prognosis from their NHL when compared to patients without autoimmune diseases. However, there is limited literature regarding the interplay of traditional NHL risk factors with underlying autoimmunity. Hence, our retrospective analysis sheds light on the lesser studied risk factors, such as patient characteristics and comorbidities. We found that older age, male sex, Asian and Pacific Islander race, family history of lymphoid malignancy, personal history of chemotherapy or radiation, and comorbidities like HIV, Viral Hepatitis, and HTLV-1 are some strong risk factors associated with the development of NHL in patients with autoimmune diseases. Infections like HIV and HTLV-1 played less of a role in the autoimmune cohort as opposed to the non-autoimmune cohort. Whereas personal histories of chemotherapy and radiation and family histories of lymphoid malignancies were demonstrated to be very strong risk factors in both settings. Hence, our study enables clinicians to identify the differences in the interplay of these risk factors and to perform stringent monitoring of patients when they do have these risk factors

Modeling historic neighborhood deprivation and non-Hodgkin lymphoma risk

Many studies have identified associations between neighborhood deprivation and disease, emphasizing the importance of social determinants of health. However, when studying diseases with long latency periods such as cancers, considering the timing of exposures for deprivation becomes more important. In this study, we estimated the associations between neighborhood deprivation indices at several time points and risk of non-Hodgkin lymphoma (NHL) in a population-based case-control study at four study centers – Detroit, Iowa, Los Angeles County, and Seattle (1998–2000). We used the Bayesian index regression model and residential histories to estimate neighborhood deprivation index effects in crude models and adjusted for four chemical mixtures measured in house dust and individual-level covariates. We found that neighborhood deprivation in 1980, approximately twenty years before study entry, provided better model fit than did neighborhood deprivation at 1990 and 2000. We identified several statistically significant associations between neighborhood deprivation in 1980 and NHL risk in Iowa and among long-term (20+ years) residents of Detroit. The most important variables in these indices were median gross rent as a percentage of household income in Iowa and percent of single-parent households with at least one child and median household income in Detroit. Associations remained statistically significant after adjustment for individual-level covariates and chemical mixtures, providing evidence for historic neighborhood deprivation as a risk factor for NHL and motivating future research to uncover the specific carcinogens driving these associations in deprived areas.

Treated chronic hepatitis B is a good prognostic factor of diffuse large B-cell lymphoma.

Chronic hepatitis B (CHB) is a risk factor for non-Hodgkin lymphoma (NHL). Our recent study suggested that antiviral treatment may reduce the incidence of NHL in CHB patients. This study compared the prognoses of hepatitis B virus (HBV)-associated diffuse large B-cell lymphoma (DLBCL) patients receiving antiviral treatment and HBV-unassociated DLBCL patients. This study comprised 928 DLBCL patients who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at two referral centers in Korea. All patients with CHB received antiviral treatment. Time-to-progression (TTP) and overall survival (OS) were the primary and secondary endpoints, respectively. Among the 928 patients in this study, 82 were hepatitis B surface antigen (HBsAg)-positive (the CHB group) and 846 were HBsAg-negative (the non-CHB group). The median follow-up time was 50.5 months (interquartile range [IQR]=25.6-69.7 months). Multivariable analyses showed longer TTP in the CHB group than the non-CHB group both before inverse probability of treatment weighting (IPTW; adjusted hazard ratio [aHR]=0.49, 95% confidence interval [CI]=0.29-0.82, p=0.007) and after IPTW (aHR=0.42, 95% CI=0.26-0.70, p<0.001). The CHB group also had a longer OS than the non-CHB group both before IPTW (HR=0.55, 95% CI=0.33-0.92, log-rank p=0.02) and after IPTW (HR=0.53, 95% CI=0.32-0.99, log-rank p=0.02). Although liver-related deaths did not occur in the non-CHB group, two deaths occurred in the CHB group due to hepatocellular carcinoma and acute liver failure, respectively. Our findings indicate that HBV-associated DLBCL patients receiving antiviral treatment have significantly longer TTP and OS after R-CHOP treatment than HBV-unassociated DLBCL patients.

Exposure to phenoxyacetic acids and glyphosate as risk factors for non-Hodgkin lymphoma– pooled analysis of three Swedish case-control studies including the sub-type hairy cell leukemia

The association between pesticide exposure and non-Hodgkin lymphoma (NHL) including hairy cell leukemia (HCL) was analyzed in a pooled study of three case-control studies. Results on exposure to pesticides were based on 1,425 cases and 2,157 controls participating in the studies. Exposures were assessed by self-administered questionnaires completed as needed by phone. In the pooled univariate analyses adjusted by age, gender and year of diagnosis, exposure to herbicides of the phenoxyacetic acid type yielded statistically significant increased risk with odds ratio (OR) = 1.9, 95% confidence interval CI) = 1.4–2.5. The herbicide glyphosate gave OR = 2.2, 95% CI = 1.3–3.8. Impregnating agents increased the risk. No clear dose-response effect was seen. OR was highest in the >10–20 years latency group for herbicides and impregnating agents. In the multivariate analysis including main pesticide groups, statistically significant increased risk was found for herbicides, OR = 1.6, 95% CI = 1.2–2.1 and impregnating agents with OR = 1.4, 95% CI = 1.1–1.8. This analysis confirmed an association between NHL including HCL and exposure to certain herbicides.

Modeling historic environmental pollutant exposures and non-Hodgkin lymphoma risk

Environmental exposures to chemicals are suspected risk factors for non-Hodgkin lymphoma (NHL), but few studies have assessed historic environmental risk factors. In this study, we estimated the associations between NHL and 1) historic environmental pollutant emissions from the Risk Screening Environmental Indicators (RSEI) model, which uses a database from the Environmental Protection Agency of toxic release emissions to air, water, and land, and 2) chemical mixtures measured in house dust (groups of PCBs, PAHs, and two mixtures of pesticides) for study participants enrolled in the NCI-SEER population-based case-control study (1998–2000) at four SEER centers – Detroit, Iowa, Los Angeles County, and Seattle. We assigned 11 years of annual temporally-varying historic environmental exposure scores by intersecting residential locations from participants' residential histories with a fine grid from the RSEI model and by performing inverse distance weighting between facilities releasing specific carcinogenic chemicals and residential locations for spatially-precise exposure assignments. We used Bayesian index low-rank kriging multiple membership models to identify important lag times for RSEI scores, cumulative effects of RSEI scores, and specific carcinogenic chemical releases into the environment. We found a significant positive association between RSEI scores and NHL at the maximum time lag of 11 years (OR = 1.17, 95% CI (1.06, 1.32)) and a significant cumulative RSEI score effect (OR = 1.30, 95% CI (1.02, 1.84)) for long-term residents in Detroit, where benzene and trichloroethylene were the most important chemicals driving this association. Additionally, we identified significant inverse associations for two study centers and time lags that did not persist in cumulative exposure models. Large weights for dichloromethane and pentachlorophenol in models of cumulative exposure also support evidence for their association with NHL risk. These results underscore the importance of considering historic and cumulative environmental exposures and using residential histories for diseases with long latency periods such as NHL.

Targeted proteomic scan identifies alteration of serum proteins among workers occupationally exposed to low levels of trichloroethylene.

Occupational exposure to trichloroethylene (TCE) has been associated with alterations in B-cell activation factors and an increased risk of non-Hodgkin's lymphoma (NHL). Here, we aimed to examine the biological processes influenced by TCE exposure to understand the underlying molecular mechanisms. This cross-sectional molecular epidemiology study included data of 1317 targeted proteins in the serum from 42 TCE exposed and 34 unexposed factory workers in Guangdong, China. We used multivariable linear regressions to identify proteins associated with TCE exposure and examined their exposure-response relationship across categories of TCE exposure (unexposed, low exposed: <10ppm, high exposed: ≥10ppm). We further examined pathway enrichment of TCE-related proteins to understand their biological response. Occupational exposure to TCE was associated with lower levels of tumor necrosis factor receptor superfamily member 17 (TNFRSF17; β=-.08; p-value=.0003) and kynureninase (KYNU; β=-.10, p-value=.002). These proteins also showed a significant exposure-response relation across the unexposed, low exposed, and high exposed workers (all p-trends < .001, false discovery rate [FDR] < 0.20). Pathway analysis of TCE-related proteins showed significant enrichment (FDR < 0.05) for several inflammatory and immune pathways. TCE exposure was associated with TNFRSF17, a key B-cell maturation antigen that mediates B-cell survival and KYNU, an enzyme that plays a role in T-cell mediated immune response. Given that altered immunity is an established risk factor for NHL, our findings support the biological plausibility of linking TCE exposure with NHL.

Environmental pesticide exposure and non-Hodgkin lymphoma survival: a population-based study

BackgroundThere is evidence indicating that pesticide exposure is a risk factor for non-Hodgkin lymphoma (NHL) development. However, the association between pesticide exposure and NHL survival is not well-established.MethodsUsing the California Cancer Registry, we identified patients with a first primary diagnosis of NHL from 2010 to 2016 and linked these patients with CalEnviroScreen 3.0 to obtain production agriculture pesticide exposure to 70 chemicals from the state-mandated Pesticide Use Reporting (PUR) by census tract from 2012 to 2014. In addition, data from PUR was integrated into a geographic information system that employs land-use data to estimate cumulative exposure to specific pesticides previously associated with NHL (glyphosate, organophosphorus, carbamate, phenoxyherbicide, and 2,4-dimethylamine salt) between 10 years prior up to 1 year after NHL diagnosis. Multivariable Cox proportional hazards regression models were used to evaluate the association between total pesticide exposure from CalEnviroScreen 3.0 and individual pesticide exposure from geographic land use data and lymphoma-specific and overall survival.ResultsAmong 35,808 NHL patients identified, 44.2% were exposed to pesticide in their census tract of residence. Glyphosate, organophosphorus, carbamate, phenoxyherbicide, and 2,4-dimethylamine salt exposure was observed in 34.1%, 26.0%, 10.6%, 14.0%, and 12.8% of NHL patients, respectively. Total pesticide exposure at the time of diagnosis was not associated with lymphoma-specific or overall survival. In addition, no association was consistently found between glyphosate, organophosphorus, carbamate, phenoxyherbicide, and 2,4 dimethylamine salt exposure and lymphoma-specific or overall survival.ConclusionsAlthough we found no consistent associations between agricultural pesticide exposure at the neighborhood level and worse survival, these results provide a platform for designing future studies to determine the association between pesticide and NHL.

Effect of Pesticide Exposure on Non-Hodgkin Lymphoma Incidence and Survival in California

Introduction:While previous studies propose pesticide exposure to be a risk factor for non-Hodgkin lymphoma (NHL) development, results are inconclusive. In addition, the impact of pesticide exposure on NHL survival is not well-established. Therefore, we identified NHL patients from the California Cancer Registry and linked these patients with the statewide pesticide use reporting database to determine the impact of pesticide exposure on NHL-related incidence and outcomes.Methods:Using the California Cancer Registry, we identified patients with a first primary diagnosis of NHL from 2010-2016 and linked these patients with CalEnviroScreen 3.0 to obtain production agriculture pesticide exposure to 70 chemicals from the state mandated Pesticide Use Reporting (PUR) by census tract from 2012-2014. In addition, data from PUR was integrated into a geographic information system that employs land use data to estimate cumulative exposure to specific pesticides previously associated with NHL (glyphosate, organophosphorus, carbamate, phenoxyherbicide and 2,4-dimethylamine salt) between 10 years prior up to 1 year after NHL diagnosis. SEER*Stat software was used to calculate NHL subtype incidence rates by census tract pesticide use level. Multivariable cox proportional hazards regression models were used to evaluate the impact of total pesticide exposure from CalEnviroScreen 3.0 and individual pesticide exposure from geographic land use data on lymphoma-specific and overall survival.Results:Among 35,808 NHL patients identified, 44.2% were exposed to pesticide in their census tract of residence. Pesticide exposure was higher in Hispanic/Latino (46.5%) and non-Hispanic white (45.6%) then Asian/Pacific Islander (37.2%) and African American (34.9%) patients with NHL. Glyphosate, organophosphorus, carbamate, phenoxyherbicide and 2,4-dimethylamine salt exposure was reported in 34.1%, 26.0%, 10.6%, 14.0% and 12.8% of NHL patients, respectively. Pesticide exposure was not associated with increased NHL incidence by NHL subtype or subgroups defined by sociodemographic factors. Total pesticide exposure at time of diagnosis was not associated with lymphoma-specific or overall survival. In addition, no association was consistently found between glyphosate, organophosphorus, carbamate, phenoxyherbicide and 2,4 dimethylamine salt exposure and lymphoma-specific or overall survival.Conclusion:In this large population-based study of neighborhood agricultural pesticide exposure, pesticide exposure was noted to be prevalent among patients diagnosed with NHL, with high pesticide exposure particularly observed in Hispanics/Latinos and non-Hispanic whites. However, pesticide exposure was not consistently associated with increased NHL incidence or worse NHL lymphoma-specific or overall survival. DisclosuresPoh: Acrotech: Honoraria; Incyte: Research Funding; Morphosys: Consultancy. Tuscano: BMS: Research Funding; Seattle Genetics: Research Funding; Takeda: Research Funding; Acrotech: Research Funding; Genentech: Research Funding; Pharmacyclics: Research Funding; Abbvie: Research Funding.

Human pegivirus 1 in Cabo Verde: prevalence and genotypic distribution among HIV-infected individuals.

Human pegivirus 1 (HPgV-1) belongs to the genus Pegivirus, family Flaviviridae, and until now has been considered a non-pathogenic agent, despite being considered a risk factor for non-Hodgkin lymphoma. However, a beneficial impact of HPgV-1 on HIV disease progression has been extensively reported. Given the high prevalence of HIV in sub-Saharan Africa and the scarcity of epidemiological data for many countries of West Africa, we conducted the first study of HPgV-1 in HIV-infected individuals from Cabo Verde. To obtain new data regarding prevalence and genetic diversity of HPgV-1 in Africa, serum samples from 102 HIV-infected Cabo Verdeans were tested for the presence of viral RNA, and the circulating genotypes were identified by sequencing of the 5' untranslated region. HPgV-1 RNA was detected in 19.6% (20/102) of the samples. In 72.2% (13/18) of the samples, the virus was identified as genotype 2 (11/13 subtype 2a and 2/13 subtype 2b), and in 27.8% (5/18), it was identified as genotype 1. The estimated substitution rate of HPgV-1 genotype 2 was 5.76 × 10-4, and Bayesian analysis indicated the existence of inner clusters within subtypes 2a and 2b. The prevalence of HPgV-1 viremia in Cabo Verde agrees with that reported previously in Africa. Genotypes 1 and 2 cocirculate, with genotype 2 being more common, and HIV/HPgV-1 coinfection was not associated with higher CD4 T cell counts in the studied population. This finding contributes for the expansion of the pegivirus research agenda in African countries.

Diagnosis of a plasmoblastic lymphoma of the mandible after renal transplantation: a case report

Introduction: Post-transplant lymphoproliferations (PTL) are a severe complication of solid organ transplants. Their locations can be extra-nodal. Observation: The diagnosis and management of a non-Hodgkin's plasmablastic lymphoma of mandibular localization affecting a 66-year-old kidney transplanted patient are reported here. Comment: The main risk factors for non-Hodgkin lymphoma are immunosuppression and infection with Epstein-Barr virus. Clinical and radiographic examinations, which are not specific, must be supplemented by a histological examination. Treatment which is not consensual will most often consist of a reduction in immunosuppression coupled with chemotherapy. Conclusion: Despite a constant evolution in the incidence and clinical picture of post-transplant lymphomas, the role of the dentist remains essential in the early detection of lesions.

The incidence of non-Hodgkin lymphoma is increased in patients with obstructive sleep apnea

Obstructive sleep apnea (OSA) is known to be associated with several cancers, but studies assessing the association between OSA and lymphoma have not been conducted yet. This study aimed to investigate the associations between OSA and non-Hodgkin lymphoma, which accounts for the majority of lymphoma, using the Korea National Health Insurance Service database. This retrospective cohort study analyzed the data from the Korea National Health Insurance Service database. A total of 198,574 patients aged ≥ 20 years who were newly diagnosed with OSA between 2007 and 2014 were included. The control group comprising 992,870 subjects was selected using propensity score matching by age and sex. The mean follow-up duration was 4.8 ± 2.3 years. The primary endpoint was newly diagnosed non-Hodgkin lymphoma. The hazard ratio [95 % confidence interval] of OSA for the incidence of non-Hodgkin lymphoma was calculated based on Cox proportional hazard model. The incidence of non-Hodgkin lymphoma among patients with OSA was significantly higher than that among the controls (1.40 [1.16–1.69]). In particular, the incidence was higher in women than that in men (1.62 vs. 1.28). There was no difference in hazard ratio by age. In conclusion, OSA may be a risk factor for non-Hodgkin lymphoma.

Fruit and Vegetable Consumption and Risk of Non-Hodgkin Lymphoma

Background: The few established risk factors for non-Hodgkin lymphoma (NHL) exhibit considerable heterogeneity by NHL subtype and suggest an etiologic role for factors with immune- or inflammation-modulating properties, or which otherwise influence lymphocyte proliferation and survival. Epidemiologic evidence supports a potential inverse association for fruit and vegetable intake and NHL risk, but with limited subtype-specific evidence. Glucosinates and indole-3-carbinol, both found in cruciferous vegetables, may mediate tumor suppressive effects, including anti-inflammatory and anti-proliferation effects or restoration of phosphatase and tensin homolog (PTEN), a known tumor suppressor frequently down-regulated in cancer cells. We conducted a prospective study to further elucidate the etiologic role of fruit and vegetable consumption for NHL and its most common histologic subtypes. Methods: We followed 47,971 men in the Health Professionals Follow-Up Study (HPFS; 1986-2012) and 77,115 women in the Nurses' Health Study (NHS; 1984-2012) with baseline information on diet and no baseline history of cancer. We queried diet every four years using validated food-frequency questionnaires. We calculated fruit and vegetable consumption, in broad categories and for specific food groups, by summing the intake of individual foods excluding fruit juices, potatoes and legumes. Incident NHL diagnoses were first self-reported in study questionnaires then confirmed by review of medical records. We classified histologic subtypes according to the World Health Organization (WHO) and International Lymphoma Epidemiology (InterLymph) Consortium guidelines. We analyzed all NHL (in aggregate) and separate endpoints of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, other B-cell NHL and T-cell NHL. We used multivariate Cox proportional hazards regression adjusting for potential confounding variables to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of various fruit and vegetable intake variables with risk of each NHL endpoint. Those intake variables were based on the pre-diagnosis questionnaire returned most recent to NHL diagnosis and modeled as continuous variables in increments of one serving/day. Results: During 2,747,939 person-years of follow-up, we confirmed 1,732 incident NHL cases (986 women, 746 men). In preliminary multivariable-adjusted analyses, no fruit and vegetable intake variable was significantly associated with risk of all NHL (Table 1). Each additional serving/day of all, green leafy, beta carotene rich and lycopene rich vegetables was significantly associated with a 15%-45% lower risk of DLBCL per serving/day but not with other NHL subtypes; cruciferous and lutein rich vegetable intakes had a suggestive but statistically non-significant inverse association with several B-cell NHL subtypes (Table 1). Other associations were only weakly suggestive or null. Conclusions: In this prospective investigation, preliminary findings suggest a modest reduction of risk of several individual B-cell NHL subtypes, including statistically significantly lower risks of DLBCL, with increasing intake of green and antioxidant rich vegetables. These findings warrant further exploration and confirmation in other study populations. We note that this abstract reports preliminary findings; ongoing analyses will extend the follow-up period, add a third large cohort (NHS II) and assess potential reverse causation, explore sex- and subtype-related heterogeneity and test for non-linearity of observed associations. If confirmed, these results will contribute to evidence-based prevention strategies for NHL and further support general health recommendations concerning benefits of fruit and vegetable intake. Disclosures No relevant conflicts of interest to declare.

A multivariable approach for risk markers from pooled molecular data with only partial overlap

BackgroundIncreasingly, molecular measurements from multiple studies are pooled to identify risk scores, with only partial overlap of measurements available from different studies. Univariate analyses of such markers have routinely been performed in such settings using meta-analysis techniques in genome-wide association studies for identifying genetic risk scores. In contrast, multivariable techniques such as regularized regression, which might potentially be more powerful, are hampered by only partial overlap of available markers even when the pooling of individual level data is feasible for analysis. This cannot easily be addressed at a preprocessing level, as quality criteria in the different studies may result in differential availability of markers – even after imputation.MethodsMotivated by data from the InterLymph Consortium on risk factors for non-Hodgkin lymphoma, which exhibits these challenges, we adapted a regularized regression approach, componentwise boosting, for dealing with partial overlap in SNPs. This synthesis regression approach is combined with resampling to determine stable sets of single nucleotide polymorphisms, which could feed into a genetic risk score. The proposed approach is contrasted with univariate analyses, an application of the lasso, and with an analysis that discards studies causing the partial overlap. The question of statistical significance is faced with an approach called stability selection.ResultsUsing an excerpt of the data from the InterLymph Consortium on two specific subtypes of non-Hodgkin lymphoma, it is shown that componentwise boosting can take into account all applicable information from different SNPs, irrespective of whether they are covered by all investigated studies and for all individuals in the single studies. The results indicate increased power, even when studies that would be discarded in a complete case analysis only comprise a small proportion of individuals.ConclusionsGiven the observed gains in power, the proposed approach can be recommended more generally whenever there is only partial overlap of molecular measurements obtained from pooled studies and/or missing data in single studies. A corresponding software implementation is available upon request.Trial registrationAll involved studies have provided signed GWAS data submission certifications to the U.S. National Institute of Health and have been retrospectively registered.

Association of Occupational Pesticide Exposure With Immunochemotherapy Response and Survival Among Patients With Diffuse Large B-Cell Lymphoma

Professional use of pesticides is a risk factor for non-Hodgkin lymphoma. The main biological mechanisms of pesticides and chemotherapy are genotoxicity and reactive oxygen species generation. Cellular adaptation among patients exposed to low doses of genotoxic and oxidative compounds might hinder chemotherapy efficiency in patients with lymphoma. To examine the association of occupational exposure to pesticides with immunochemotherapy response and survival among patients treated for diffuse large B-cell lymphoma. This retrospective cohort study assessed patients treated from July 1, 2010, to May 31, 2015, for diffuse large B-cell lymphoma, with a 2-year follow-up. The study took place at 6 university and nonuniversity hospitals in Languedoc-Roussillon, France. A total of 404 patients with newly diagnosed diffuse large B-cell lymphoma treated with anthracycline-based immunochemotherapy were included before the study began. Occupational history was reconstructed for 244 patients and analyzed with the PESTIPOP French job-exposure matrix to determine likelihood of occupational exposure to pesticides. Analysis of the data was performed from July 15, 2017, to July 15, 2018. Treatment failure (ie, partial response, stable disease, disease progression, or interruption for toxic effects) rate, 2-year event-free survival, and overall survival between exposed and nonexposed patients after adjustment for confounding factors. A total of 244 patients (mean [SD] age, 61.3 [15.2] years; 153 [62.7%] male) had complete occupational data. Of these patients, 67 (27.4%) had occupational exposure to pesticides, with 38 exposed through agricultural occupations. Occupational exposure was not associated with clinical and biological characteristics at diagnosis. Occupationally exposed patients had a significantly higher treatment failure rate (22.4% vs 11.3%; P = .03; adjusted odds ratio [AOR] for confounding factors, 3.0; 95% CI, 1.3-6.9); this difference was higher among patients with exposing agricultural occupations compared with other patients (29.0% vs 11.7%; AOR, 5.1; 95% CI, 2.0-12.8). Two-year event-free survival was 70% in the occupationally exposed group vs 82% in the unexposed group (adjusted hazard ratio [AHR] for confounding factors, 2.2; 95% CI, 1.3-3.9). Among patients with exposing agricultural occupations compared with other patients, the difference was more pronounced (2-year event-free survival, 56% vs 83%; AHR, 3.5; 95% CI, 1.9-6.5). Similarly, 2-year overall survival was lower in the group of patients with exposing agricultural occupations compared with other patients (81% vs 92%; AHR, 3.9; 95% CI, 1.5-10.0). This retrospective study showed that agricultural occupational exposure to pesticides was associated with treatment failure, event-free survival, and overall survival among patients with diffuse large B-cell lymphoma.

Hepatitis C virus infection is a risk factor for non-Hodgkin lymphoma: A MOOSE-compliant meta-analysis.

Previous studies have reached conflicting results regarding the possibility that hepatitis C virus (HCV) infection may increase the risk of non-Hodgkin lymphoma (NHL). We performed a meta-analysis to clarify the relationship between HCV infection and development of NHL. The PubMed, Web of Science, and Embase databases were searched for relevant studies estimating the association between HCV infection and NHL risk through October 31, 2017. Fixed effects or random effects models were used to calculate the pooled odds ratio (OR) and its 95% confidence interval (CI). A total of 18 studies met the inclusion criteria. We found a positive association between HCV infection and NHL (pooled OR 1.69, 95% CI 1.40–2.03, P < .05). In conclusion, our meta-analysis suggested that HCV infection was associated with increased risk of developing NHL.

Anthropometric Traits and Risk of Non-Hodgkin Lymphoma (NHL) and Major NHL Subtypes: A Pooled Prospective Analysis

Background: Collectively, non-Hodgkin lymphomas (NHL) are expected to account for >95,000 new cancer diagnoses and >24,000 cancer deaths in the United States in 2018. Few NHL risk factors are known other than severe immune compromise, family history of lymphoid malignancies, and some pathogens. Evidence for modifiable risk factors that could inform prevention strategies is limited, especially from prospective studies. An association of anthropometric traits with NHL risk is biologically plausible given the emerging knowledge that obese individuals have heightened inflammation and deregulation of endogenous hormonal pathways that can influence cell cycle control and lymphocyte activation. We undertook the present prospective study to elucidate the associations of young (aged 18-21 years) and usual adult body mass index (BMI), height, weight, and waist circumference with risk of NHL and major histologic subtypes of NHL. The completed analysis will leverage the resources of several large population samples across the United States with prospectively assessed repeated measures of anthropometric traits and high rates of follow-up for disease ascertainment.Methods: We pooled data from large prospective cohort studies with repeated measures of anthropometric traits and follow-up over 23 - 38 years for cancer endpoints, including the Cancer Prevention Study-II (CPS-II) Nutrition Cohort, Health Professionals Follow-up Study (HPFS), Nurses' Health Study (NHS), and NHS II. Incident NHL diagnoses were confirmed by review of medical records or cancer registries, and classified for histologic subtype according to the WHO classification scheme and corresponding InterLymph-recommended analytic groups: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and T-cell NHL (T-NHL). Weight was ascertained approximately every two years throughout follow-up, all other anthropometric measures were ascertained on a single survey, usually at baseline. We considered cumulative average of BMI (hereafter “usual adult BMI”) by averaging across all completed cohort-specific questionnaires. Current weight was analyzed as time-varying. In cohort- and sex-specific analyses, there was no evidence of statistically significant heterogeneity; thus we pooled directly across cohorts to maximize our sample size for statistical modeling. Cox proportional hazard regression models adjusted for age, cohort, and sex were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for each trait's association with NHL or NHL subtype risk.Results: The pooled sample comprised 5,005 confirmed incident cases of NHL, including 1117 CLL/SLL, 918 DLBCL, 709 FL and 277 T-NHLs ascertained over 9.4 million person-years of follow-up. There was a significant, positive association of usual adult BMI with NHL overall (HR: 1.05, 95% CI: 1.01-1.08 per 5 kg/m2; Table 1), which was driven by DLBCL (HR: 1.21, 95% CI: 1.12-1.30 per 5 kg/m2). No association was apparent for FL, CLL/SLL or T-NHL. Similarly, waist circumference was associated with NHL risk overall (HR: 1.04, 95% CI: 1.00-1.09 per 15cm), but driven by the association for DLBCL (HR: 1.16, 95% CI: 1.05-1.27 per 15cm). In contrast, a statistically significant or suggestive association for BMI in young adulthood was observed for all NHL endpoints, but again, most strongly with DLBCL (HR: 1.28, 95% CI: 1.15-1.43 per 5 kg/m2). Height was positively associated with all NHL endpoints except T-NHL. Associations for current and young adult weight were similar to those for the corresponding BMI variables.Conclusions: Preliminary results from this prospective analysis suggest that, unlike BMI later in life, young adult BMI is consistently associated with all major subtypes of NHL. In contrast, usual adult BMI and waist circumference are uniquely associated with DLBCL. In general, the strongest associations with anthropometric factors were observed for DLBCL. Further analyses of these data are ongoing, including efforts to incorporate data from two additional large cohorts. These findings further demonstrate the etiologic heterogeneity of NHL subtypes and underscore the importance of maintaining a healthy body weight throughout life, including at younger ages. [Display omitted] DisclosuresChao:Seattle Genetics: Research Funding.

Prognosis of diffuse large B cell lymphoma related to occupational exposure to pesticides: A cohort study

Summary Importance Professional use of pesticides is a risk factor for non-Hodgkin lymphoma. The main biological mechanisms of both pesticides and chemotherapy are genotoxicity and reactive oxygen species generation. Cellular adaptation among patients exposed to low doses of genotoxic and oxidative compounds may hinder chemotherapy efficiency in lymphoma patients. Objective We aim to determine the influence of occupational exposure to pesticides on response to immuno-chemotherapy and survival of patients treated for Diffuse Large B Cell Lymphoma (DLBCL). Design The ProLyPhy study is a retrospective cohort of patients treated between 2010 and mid-2015, for DLBCL, with a least 2-year follow-up. Setting The study took place in six hospitals of central southern France (Languedoc-Roussillon district): two university hospitals, three general hospitals, and one private hospital. Participants We pre-included 404 patients with newly-diagnosed DLBCL treated with anthracycline-based immuno-chemotherapy (R-CHOP like). Occupational history was reconstructed for 244 patients. Occupational data were analysed with the Pestipop French job-exposure matrix to determine probability of occupational exposure to pesticides, and with the Pestimat French crop exposure matrix for farming activities to characterise the probability of using specific compounds. Main outcome and measure We have compared complete response (CR), 2-year event-free survival (EFS) and overall survival (OS) of exposed and non-exposed patients, after adjustment on confounding factors. Results Average age was 61.3 years (range 19–90), 62.7% of patients were male, 67 had occupational exposure to pesticides, of which 38 from farming activities. Occupational exposure did not impact clinical and biological characteristics at diagnostic. We observed that exposed patients had significantly lower CR rate: 77.6% versus 88.7% (P = 0.027), OR = 0.31 (0.55–0.09, P = 0.007); this difference was higher among farmers: 68.6% CR versus 87.2%, P = 0.005, OR = 0.22 (0.56–0.09, P = 0.001). Two-year EFS was 70% in the occupationally-exposed group versus 82%, HR = 2.1 (95% CI: 1.2–3.6, P = 0.008). Among farmers, the difference was more pronounced: 2-year EFS was 56% versus 83%, HR = 3.1 (95% CI: 1.7–5.6, P Conclusion and relevance This retrospective study suggests that agricultural occupational exposure to pesticides is an independent risk factor for treatment failure, EFS and OS in DLBCL. Trial registration The study was registered in ClinicalTrials.gov ( NCT02898870 ).

Occupational exposure to pesticides and prognosis of diffuse large B-cell lymphoma: A cohort study.

1564Background: Professional use of pesticides is a risk factor for non-Hodgkin lymphoma. The main biological mechanisms of both pesticides and chemotherapy are genotoxicity and reactive oxygen spe...

C677T and A1298C polymorphisms of methylene tetrahydrofolate reductase in non-Hodgkin lymphoma: southeast Iran.

Polymorphisms of the methylene tetrahydrofolate reductase (MTHFR) gene have been reported as risk factors for non-Hodgkin lymphoma (NHL) in some populations. Our goal was to evaluate the potential role of A1298C and C677T polymorphisms of MTHFR in risk of NHL in southeast Iran. In the present case-control study, 127 patients with newly diagnosed NHL along with 150 ethnicity- and age-matched controls were examined. The A1298C and C677T polymorphisms were genotyped using the Tetra Amplification Refractory Mutation System polymerase chain reaction method. There were no significant differences in genotype frequencies between cases and controls regarding either A1298C polymorphism. For this polymorphism, 53.8% of the controls and 54.3% of the patients with NHL showed homozygous wild-type (AA) genotype. Variant 1298C allele was recognized with overall frequency of 34.6% in both groups. Frequencies of CC, CT, and TT genotypes of C677T polymorphism were observed in 73.1%, 25.8%, and 1.3% of the controls, and 64.5%, 33.1%, and 2.4% of the patients with NHL (p>0.05). In combination, CT + TT conferred a significantly higher risk of NHL (odds ratio [OR] 1.5, 95% confidence interval [CI] 0.9-2.4, p = 0.03). Overall, variant 677T allele presented with higher frequency in the patients with NHL than the controls (26.7% versus 21.3%, respectively; OR 1.3, 95% CI 0.8-2.1, p>0.05). Although statistically insignificant, the highest risk of NHL was identified in patients with C677T; A1298C: CT; CC haplotype (OR 4.7, 95% CI 0.4-46.4, p = 0.1). Combination of CT and TT genotypes of C677T polymorphism conferred a significantly higher risk for NHL. It is recommended to investigate further the potential role of this polymorphism in NHL development.