Risk Of non-Hodgkin Lymphoma Subtypes Research Articles

Insecticide use and risk of non-Hodgkin lymphoma subtypes: A subset meta-analysis of the North American Pooled Project.

Insecticide use has been linked to increased risk of non‐Hodgkin lymphoma (NHL), however, findings of epidemiologic studies have been inconsistent, particularly for NHL subtypes. We analyzed 1690 NHL cases and 5131 controls in the North American Pooled Project (NAPP) to investigate self‐reported insecticide use and risk of NHL overall and by subtypes: follicular lymphoma (FL), diffuse large B‐cell lymphoma (DLBCL) and small lymphocytic lymphoma (SLL). Odds ratios (OR) and 95% confidence intervals for each insecticide were estimated using logistic regression. Subtype‐specific associations were evaluated using ASSET (Association analysis for SubSETs). Increased risks of multiple NHL subtypes were observed for lindane (OR = 1.60, 1.20‐2.10: FL, DLCBL, SLL), chlordane (OR = 1.59, 1.17‐2.16: FL, SLL) and DDT (OR = 1.36, 1.06‐1.73: DLBCL, SLL). Positive trends were observed, within the subsets with identified associations, for increasing categories of exposure duration for lindane (P trend = 1.7 × 10−4), chlordane (P trend = 1.0 × 10−3) and DDT (P trend = 4.2 × 10−3), however, the exposure‐response relationship was nonlinear. Ever use of pyrethrum was associated with an increased risk of FL (OR = 3.65, 1.45‐9.15), and the relationship with duration of use appeared monotonic (OR for >10 years: OR = 5.38, 1.75‐16.53; P trend = 3.6 × 10−3). Our analysis identified several novel associations between insecticide use and specific NHL subtypes, suggesting possible etiologic heterogeneity in the context of pesticide exposure.

Lipid Trait Variants and the Risk of Non-Hodgkin Lymphoma Subtypes: A Mendelian Randomization Study.

Lipid traits have been inconsistently linked to risk of non-Hodgkin lymphoma (NHL). We examined the association of genetically predicted lipid traits with risk of diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and marginal zone lymphoma (MZL) using Mendelian randomization (MR) analysis. Genome-wide association study data from the InterLymph Consortium were available for 2,661 DLBCLs, 2,179 CLLs, 2,142 FLs, 824 MZLs, and 6,221 controls. SNPs associated (P < 5 × 10-8) with high-density lipoprotein (HDL, n = 164), low-density lipoprotein (LDL, n = 137), total cholesterol (TC, n = 161), and triglycerides (TG, n = 123) were used as instrumental variables (IV), explaining 14.6%, 27.7%, 16.8%, and 12.8% of phenotypic variation, respectively. Associations between each lipid trait and NHL subtype were calculated using the MR inverse variance-weighted method, estimating odds ratios (OR) per standard deviation and 95% confidence intervals (CI). HDL was positively associated with DLBCL (OR = 1.14; 95% CI, 1.00-1.30) and MZL (OR = 1.09; 95% CI, 1.01-1.18), while TG was inversely associated with MZL risk (OR = 0.90; 95% CI, 0.83-0.99), all at nominal significance (P < 0.05). A positive trend was observed for HDL with FL risk (OR = 1.08; 95% CI, 0.99-1.19; P = 0.087). No associations were noteworthy after adjusting for multiple testing. We did not find evidence of a clear or strong association of these lipid traits with the most common NHL subtypes. While these IVs have been previously linked to other cancers, our findings do not support any causal associations with these NHL subtypes. Our results suggest that prior reported inverse associations of lipid traits are not likely to be causal and could represent reverse causality or confounding.

Risk of non-Hodgkin lymphoma subtypes in HIV-infected people during the HAART era: a population-based study.

HIV-infected people have greatly elevated risk of non-Hodgkin lymphoma (NHL), particularly the AIDS-defining NHL subtypes: diffuse large B-cell lymphoma, Burkitt lymphoma and primary lymphomas arising in the central nervous system. The goals of this analysis were to comprehensively describe risks of NHL subtypes, especially those not well studied, among HIV/AIDS patients; examine risks specifically in the HAART era; and distinguish risks in HIV-infected individuals prior to diagnosis with AIDS. Population-based registry linkage study. We used data from the US HIV/AIDS Cancer Match Study from 1996 to 2010 (N = 273 705) to calculate standardized incidence ratios (SIRs) comparing subtype-specific NHL risks in HIV-infected people to those in the general population, and used Poisson regression to test for differences in SIRs between the HIV-only and AIDS periods. NHL risk was elevated 11-fold compared to the general population, but varied substantially by subtype. AIDS-defining NHL subtypes comprised the majority, and risks were high (SIRs ≥17), but risks were also increased for some T-cell lymphomas (SIRs = 3.6-14.2), marginal zone lymphoma (SIR = 2.4), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (SIR = 3.6), and acute lymphoblastic leukemia/lymphoma (SIR = 2.4). HIV-infected people in the HAART era continue to have elevated risk of AIDS-defining NHL subtypes, highlighting the contribution of moderate and severe immunosuppression to their cause. Whereas non-AIDS-defining subtypes are much less common, immunosuppression or other dysregulated immune states likely play a role in the cause of some T-cell lymphomas, marginal zone lymphoma, lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, and acute lymphoblastic leukemia/lymphoma.

Smoking, variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2), and risk of non-Hodgkin lymphoma: a pooled analysis within the InterLymph consortium

Studies of smoking and risk of non-Hodgkin lymphoma (NHL) have yielded inconsistent results, possibly due to subtype heterogeneity and/or genetic variation impacting the metabolism of tobacco-derived carcinogens, including substrates of the N-acetyltransferase enzymes NAT1 and NAT2. We conducted a pooled analysis of 5,026 NHL cases and 4,630 controls from seven case-control studies in the international lymphoma epidemiology consortium to examine associations between smoking, variation in the N-acetyltransferase genes NAT1 and NAT2, and risk of NHL subtypes. Smoking data were harmonized across studies, and genetic variants in NAT1 and NAT2 were used to infer acetylation phenotype of the NAT1 and NAT2 enzymes, respectively. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for risk of NHL and subtypes were calculated using joint fixed effects unconditional logistic regression models. Current smoking was associated with a significant 30% increased risk of follicular lymphoma (n=1,176) but not NHL overall or other NHL subtypes. The association was similar among NAT2 slow (OR 1.36; 95% CI 1.07-1.75) and intermediate/rapid (OR 1.27; 95% CI 0.95-1.69) acetylators (p (interaction)=0.82) and also did not differ by NAT1*10 allelotype. Neither NAT2 phenotype nor NAT1*10 allelotype was associated with risk of NHL overall or NHL subtypes. The current findings provide further evidence for a modest association between current smoking and follicular lymphoma risk and suggest that this association may not be influenced by variation in the N-acetyltransferase enzymes.

Antibiotic use and risk of non‐hodgkin lymphomas

Clinical case reports have suggested that specific bacterial infections are associated with certain non-Hodgkin lymphoma (NHL) subtypes. Epidemiological case-control studies have been conducted using antibiotics as a proxy for bacterial infections, but with inconclusive results. The aim of this study was, in a cohort design, based on the unique nationwide Danish registers, to investigate the association between use of antibiotics and the risk of NHL subtypes. On the basis of the Civil Registration System, we established a cohort of the entire adult (≥ 15 years) Danish population. Information on use of antibiotics came from the Danish Drug Prescription Registry and lymphoma diagnosis from the Danish Cancer Registry. Associations were assessed by adjusted rate ratios (RRs). In total, 13,602 patients were diagnosed with one of the NHL subtypes during 51.6 million person-years of follow-up (1995-2008). We observed positive associations between use of antibiotics and plasma cell myeloma [RR = 1.11, 95% confidence intervals (CIs) = 1.00-1.24], chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (RR = 1.32, 95% CI = 1.20-1.45), mantle cell lymphoma (MCL) (RR = 1.40, 95% CI = 1.04-1.88) and anaplastic large T-cell lymphoma (ALCL) (RR = 1.83, 95% CI = 1.00-3.36). Among these, the increased risk of CLL/SLL, MCL and ALCL, respectively, did not vary by years since use, and only the risk of CLL/SLL risk differed by number of prescriptions. While causality could not be established in our study, an intriguing positive long-term association between antibiotic use and CLL/SLL risk was observed. To what extent these findings indicate a role for bacteria in lymphoma pathogenesis requires further investigation.

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

AbstractSome 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.

Nutrients Contributing to One-Carbon Metabolism and Risk of Non-Hodgkin Lymphoma Subtypes

Because little is known about the etiology of non-Hodgkin lymphoma (NHL), a heterogeneous disease, and because dietary factors are modifiable, the authors examined the associations between nutrients related to one-carbon metabolism and risk of NHL in a population-based case-control study of Connecticut women diagnosed between 1996 and 2000. A total of 594 cases and 710 controls completed a food frequency questionnaire for determination of intakes of folate, vitamins B(2), B(6), and B(12), and methionine. Through unconditional logistic regression, the authors estimated the risk of NHL associated with intake of each nutrient. Comparing the highest quartile of intake with the lowest, the authors found lower risks of all NHL associated with increasing intakes of folate and methionine. Analysis by NHL subtype indicated lower risks of diffuse large B-cell lymphoma (highest quartile vs. lowest: odds ratio (OR) = 0.54, 95% confidence interval (CI): 0.30, 0.98; p-trend = 0.02) and marginal zone lymphoma (highest quartile vs. lowest: OR = 0.08, 95% CI: 0.02, 0.26; p-trend < 0.0001) associated with folate. Vitamin B(6) intake was also associated with lower risk of NHL overall and of marginal zone lymphoma (highest quartile vs. lowest: OR = 0.23, 95% CI: 0.08, 0.65; p-trend = 0.002). These findings suggest that these nutrients may be important for susceptibility to NHL.

Cigarette smoking and risk of non-Hodgkin lymphoma subtypes among women.

Previous studies of the relationship between cigarette smoking and non-Hodgkin lymphoma (NHL) have yielded conflicting results, perhaps because most studies have evaluated the risk for all NHL subtypes combined. Data from a population-based case–control study conducted among women in Connecticut were used to evaluate the impact of cigarette smoking on the risk of NHL by histologic type, tumour grade, and immunologic type. A total of 601 histologically confirmed, incident cases of NHL and 718 population-based controls provided in-person interviews. A standardised, structured questionnaire was used to collect information on each subject's current smoking status, age at initiation, duration and intensity of smoking, and cumulative lifetime exposure to smoking. Our data suggest that cigarette smoking does not alter the risk of all NHL subtypes combined. However, increased risk of follicular lymphoma appears to be associated with increased intensity and duration of smoking, and cumulative lifetime exposure to smoking. Compared with nonsmokers, women with a cumulative lifetime exposure of 16–33 pack-years and 34 pack-years or greater experience 50% increased risk (OR=1.5, 95% CI 0.9–2.5) and 80% increased risk (OR=1.8, 95% CI 1.1–3.2), respectively, of follicular lymphoma (P for linear trend=0.05). Our study findings are consistent with several previous epidemiologic studies suggesting that cigarette smoking increases the risk of follicular lymphoma. This research highlights the importance of distinguishing between NHL subtypes in future research on the aetiology of NHL.

Smoking and Risk of Non-Hodgkin Lymphoma Subtypes in a Cohort of Older Women

Although non-Hodgkin lymphoma (NHL) has not been considered to be a smoking-related malignancy, recent investigations suggest otherwise. We evaluated this association in a cohort of 37,336 women, aged 55-69 years, who reported in a mailed questionnaire in 1986 information regarding smoking history as well as demographic, medical history and dietary factors. Cancer and mortality experience through 1996 was determined by linkage to the Iowa Cancer Registry and other databases; there were 200 incident cases of NHL during the 380231 total person-years of follow-up. Compared to never smokers, former (age-adjusted RR = 1.0; 95% CI 0.8-1.5) and current smokers (age-adjusted RR = 1.0; 95% CI 0.7-1.5) were not at elevated risk of NHL, and there was no trend with pack-years smoked (ptrend = 0-3)- Multivariate adjustment for other NHL risk factors did not alter these findings. Age-adjusted analysis by NHL subtype revealed a suggestive positive association of smoking with follicular NHL (RRformer= 1.3; 95% CI 0.6-2.8), (RRcurrent = 1.8; 95% CI 0.8-3.8)], which strengthened after multivariate adjustment [(RRformer = 1.6; 95% CI 0.7-3.4), (RRcurrent = 2.3; 95% CI 1.0-5.0)]; there was no association for diffuse or small cleaved-cell NHL. Our study findings, which are consistent with other recent investigations, suggest that smoking may be associated with an increased risk of follicular NHL.