Elevated Risk Of non-Hodgkin Lymphoma Research Articles

Human Immunodeficiency Virus Related Non-Hodgkin's Lymphoma.

Human immunodeficiency virus infection is related with an increased risk of hematological malignancy principally, non-Hodgkin lymphoma. Most non-Hodgkin lymphomas are acquired immunodeficiency syndrome defining and constitute greater than 50% of all acquired immunodeficiency syndrome defining cancers. The main pathogenesis mechanisms are immunodeficiency, chronic antigenic stimulation, and the ability to infect cancer cells causing direct carcinogenesis. Human immunodeficiency virus related non-Hodgkin lymphomas are heterogeneous in immunophenotyping and molecular features; and choice of drug treatments is similar with sporadic types. The main objective is to assess the epidemiology, pathogenesis, and morphology of human immunodeficiency virus related non-Hodgkin lymphoma. The searching strategy was done by searching relevant original and review articles from www.biosemanticjane/org, Google scholar, Google, and PubMed sites using keywords like; Acquired immunodeficiency syndrome, Human immunodeficiency virus, and non-Hodgkin lymphoma. In conclusion, human immunodeficiency virus infected people continue to have elevated risk of non-Hodgkin lymphoma. Diffuse large B-cell lymphomas are the most common and severe subtype. The pathogenesis of this type of lymphoma is associated with chromosomal abnormalities that deregulate the expression of various oncogenes by different viral particles and cytokines. However, the role of these viral particles and cytokines on pathogenesis is not clearly stated, so further study could be required.

Ethylene oxide emissions and risk of breast cancer and Non-Hodgkin lymphoma in a large U.S. cohort

BACKGROUND AND AIM: Ethylene oxide (EtO) is a carcinogenic gas used to sterilize medical equipment; emissions increased during the COVID-19 pandemic. We investigated the relationship between environmental EtO exposure and risk of two {a priori} suspect cancers based on limited occupational studies. METHODS: Using the U.S. Environmental Protection Agency’s Toxic Release Inventory (TRI), we estimated historical exposures (1987-1995) at the address of NIH-AARP Diet and Health Study participants enrolled in 1995-1996. We computed distance-weighted average emissions indices (AEI=∑[lbs EtO/km²]) reflecting the sum of annual EtO emissions for all TRI facilities within 3,5, or 10km of the residence, and further weighted AEIs by the proportion of time the home was downwind of each facility. We evaluated incident Non-Hodgkin lymphoma (NHL) in the full cohort (N=451,945) and breast cancer (invasive and {in situ}) among postmenopausal women (N=173,670), overall and by subtype and disease characteristics. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for AEI categories versus no exposure in Cox models adjusting for demographic and site-specific potential confounders. RESULTS:A total of 3,796 breast cancers and 1,671 NHL cases were diagnosed through 2011. We observed a non-significantly increased risk of breast cancer overall among those in the 95th percentile of the AEI within 3km (HR[P95.vs.0]=1.48,CI=0.93-2.35). Risk of breast cancer {in situ} increased with the AEI (p-trend0.03 at 3,5, and 10km), and the strength of the association declined with increasing distance from the home (HRs[Q4.vs.0]=1.67,1.55,1.29, respectively). No statistically significant associations were found by extent of disease or by hormone receptor status. At 5km, we found an elevated risk of NHL driven by a non-monotonic increase in follicular lymphoma (p-trend=0.11). CONCLUSIONS:Our novel study suggests a positive association between EtO emissions and risk of {in situ}, but not invasive, breast cancer; differences by stage may have mechanistic implications. Inconsistent patterns of risk for NHL subtypes warrant additional evaluation. KEYWORDS: cancer and cancer precursors, long-term exposure, chemical exposures, environmental epidemiology

Occupation and Risk of Non-Hodgkin Lymphoma and Its Subtypes: A Pooled Analysis from the InterLymph Consortium.

Background:Various occupations have been associated with an elevated risk of non-Hodgkin lymphoma (NHL), but results have been inconsistent across studies.Objectives:We investigated occupational risk of NHL and of four common NHL subtypes with particular focus on occupations of a priori interest.Methods:We conducted a pooled analysis of 10,046 cases and 12,025 controls from 10 NHL studies participating in the InterLymph Consortium. We harmonized the occupational coding using the 1968 International Standard Classification of Occupations (ISCO-1968) and grouped occupations previously associated with NHL into 25 a priori groups. Odds ratios (ORs) adjusted for center, age, and sex were determined for NHL overall and for the following four subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and peripheral T-cell lymphoma (PTCL).Results:We confirmed previously reported positive associations between NHL and farming occupations [field crop/vegetable farm workers OR = 1.26; 95% confidence interval (CI): 1.05, 1.51; general farm workers OR = 1.19; 95% CI: 1.03, 1.37]; we also confirmed associations of NHL with specific occupations such as women’s hairdressers (OR = 1.34; 95% CI: 1.02, 1.74), charworkers/cleaners (OR = 1.17; 95% CI: 1.01, 1.36), spray-painters (OR = 2.07; 95% CI: 1.30, 3.29), electrical wiremen (OR = 1.24; 95% CI: 1.00, 1.54), and carpenters (OR = 1.42; 95% CI: 1.04, 1.93). We observed subtype-specific associations for DLBCL and CLL/SLL in women’s hairdressers and for DLBCL and PTCL in textile workers.Conclusions:Our pooled analysis of 10 international studies adds to evidence suggesting that farming, hairdressing, and textile industry–related exposures may contribute to NHL risk. Associations with women’s hairdresser and textile occupations may be specific for certain NHL subtypes.Citation:‘t Mannetje A, De Roos AJ, Boffetta P, Vermeulen R, Benke G, Fritschi L, Brennan P, Foretova L, Maynadié M, Becker N, Nieters A, Staines A, Campagna M, Chiu B, Clavel J, de Sanjose S, Hartge P, Holly EA, Bracci P, Linet MS, Monnereau A, Orsi L, Purdue MP, Rothman N, Lan Q, Kane E, Seniori Costantini A, Miligi L, Spinelli JJ, Zheng T, Cocco P, Kricker A. 2016. Occupation and risk of non-Hodgkin lymphoma and its subtypes: a pooled analysis from the InterLymph Consortium. Environ Health Perspect 124:396–405; http://dx.doi.org/10.1289/ehp.1409294

An Evaluation Of Glyphosate Use And The Risks Of Non-Hodgkin Lymphoma Major Histological Sub-Types In The North American Pooled Project (Napp)

Objectives: Glyphosate is a commonly used herbicide worldwide. Some epidemiological studies have linked exposure with the development of non-Hodgkin lymphoma (NHL), a group of cancers with distinct risk factors and etiologies. This study aimed to evaluate possible associations between glyphosate exposure and NHL risk. Methods: The NAPP, composed of pooled case-control studies from the US and Canada, includes NHL cases (N=1690) and controls (N=5131) who provided information on pesticide use. Cases (follicular lymphoma [FL], diffuse large B-cell lymphoma [DLBCL], small lymphocytic lymphoma [SLL], other) from cancer registries and hospitals were frequency-matched to population-based controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) by ever/never, duration, frequency, and lifetime days of glyphosate use. Models were adjusted for age, sex, location, proxy respondent, family history of lymphatohematopoietic cancer, and personal protective equipment. Results: Cases who ever used glyphosate had elevated NHL risk overall (OR=1.51, 95% CI: 1.18, 1.95). The highest risks were found for “other” sub-types (OR=1.91, 95% CI: 1.20, 3.04). Subjects who used glyphosate for =5 years had increased SLL risk (OR=2.58, 95% CI: 1.03, 6.48). Compared to non-handlers, those who handled glyphosate for =2 days/year had significantly elevated odds of NHL overall (OR=2.66, 95% CI: 1.61, 4.40) and FL (OR=2.36, 95% CI: 1.06, 5.29), DLBCL (OR=3.11, 95% CI: 1.61, 6.00), and other (OR=2.99, 95% CI: 1.10, 8.09) sub-types. There were suggestive increases in NHL risk overall with more lifetime days of use but this trend was not statistically significant (p=0.065). Conclusion: This study provides some evidence that glyphosate use may be associated with increased NHL risk. Effects may differ by histological sub-type. The large sample size of the NAPP enabled a detailed investigation despite some inconsistent results across different exposure metrics.

Non-hodgkin lymphoma risk and insecticide, fungicide and fumigant use in the agricultural health study.

Farming and pesticide use have previously been linked to non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). We evaluated agricultural use of specific insecticides, fungicides, and fumigants and risk of NHL and NHL-subtypes (including CLL and MM) in a U.S.-based prospective cohort of farmers and commercial pesticide applicators. A total of 523 cases occurred among 54,306 pesticide applicators from enrollment (1993–97) through December 31, 2011 in Iowa, and December 31, 2010 in North Carolina. Information on pesticide use, other agricultural exposures and other factors was obtained from questionnaires at enrollment and at follow-up approximately five years later (1999–2005). Information from questionnaires, monitoring, and the literature were used to create lifetime-days and intensity-weighted lifetime days of pesticide use, taking into account exposure-modifying factors. Poisson and polytomous models were used to calculate relative risks (RR) and 95% confidence intervals (CI) to evaluate associations between 26 pesticides and NHL and five NHL-subtypes, while adjusting for potential confounding factors. For total NHL, statistically significant positive exposure-response trends were seen with lindane and DDT. Terbufos was associated with total NHL in ever/never comparisons only. In subtype analyses, terbufos and DDT were associated with small cell lymphoma/chronic lymphocytic leukemia/marginal cell lymphoma, lindane and diazinon with follicular lymphoma, and permethrin with MM. However, tests of homogeneity did not show significant differences in exposure-response among NHL-subtypes for any pesticide. Because 26 pesticides were evaluated for their association with NHL and its subtypes, some chance finding could have occurred. Our results showed pesticides from different chemical and functional classes were associated with an excess risk of NHL and NHL subtypes, but not all members of any single class of pesticides were associated with an elevated risk of NHL or NHL subtypes. These findings are among the first to suggest links between DDT, lindane, permethrin, diazinon and terbufos with NHL subtypes.

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.

0324 Occupational exposure to benzene and risk of non-Hodgkin lymphoma in a population-based cohort study of Chinese women in Shanghai0324 Occupational exposure to benzene and risk of non-Hodgkin lymphoma in a population-based cohort study of Chinese women in Shanghai

ObjectivesThe association between benzene exposure and non-Hodgkin lymphoma (NHL) has been the subject of debate, and an IARC working group recently concluded for the first time that there is now...

Spatial–temporal analysis of non-Hodgkin lymphoma risk using multiple residential locations

Exploring spatial–temporal patterns of disease incidence and mortality can identify areas of significantly elevated or decreased risk, providing potential etiologic clues. Several methodological issues arise in spatial–temporal analysis of cancer, including population mobility, disease latency, and confounding, but applying modern statistical methods to case-control studies with residential histories can address these issues. As an example, we present a spatial–temporal analysis of non-Hodgkin lymphoma (NHL) risk using data from Los Angeles County, one of four centers in a population-based case-control study. Using residential histories, we fitted generalized additive models (GAMs) adjusted for known risk factors to model spatially the probability that an individual had NHL and identify areas of significantly elevated NHL risk. In previous analyses using models with single lag times, the lag time of 20years yielded the most significant decrease in model deviance. To better assess cumulative effects of unmeasured environmental exposures over space and time, we considered models that allowed for multiple residences per subject through spatial smoothing functions of residential location at different times. We found that the model with the best goodness-of-fit included components for residential change and residential duration, although the model that included residential duration was not meaningfully better than the model that included only residential change. The estimated cumulative spatial risk surface from the model with residential change amplified the risk surface in some areas compared with the surface based on the model with a single component for the most significant time lag.

Abstract 4490: Molecular characteristics of diffuse large B-cell lymphoma in HIV-positive and HIV-negative patients

Abstract Introduction: HIV-infected patients are at elevated risk of non-Hodgkin lymphoma (NHL), especially diffuse large B-cell lymphoma (DLBCL), compared with the general population. Because DLBCL is a molecularly and clinically heterogeneous disease, we compared frequencies and prognostic significance of molecular characteristics in HIV+ and HIV- DLBCLs. Methods: Archived formalin-fixed paraffin-embedded tissue specimens from 175 patients with primary DLBCL diagnosed during 1977-2003 were obtained from the Los Angeles County SEER Residual Tissue Repository. Immunohistochemistry was used to evaluate expression of key markers of B-cell differentiation, and fluorescence in situ hybridization was used to detect common NHL-associated translocations involving BCL2, BCL6, and c-Myc [t(14;18)(q32;q21), (t(3;14)(q27;q32), and t(8;14)(q24;q32), respectively]. DLBCLs were distinguished by cell of origin into germinal center B-cell (GCB)-DLBCL and activated B-cell (ABC)-DLBCL according to expression of CD10, GCET1, MUM1, FoxP1, and LMO2 based on the Tally algorithm (Meyer et al., J Clin Oncol 2011). Multivariate Cox regression compared survival according to HIV, cell of origin, and translocation status, adjusting for race/ethnicity, sex, socioeconomic status, age, Los Angeles residence, and initial course of treatment (immunochemotherapy and/or radiotherapy). Results: We identified 54 HIV+ and 121 HIV- patients with DLBCL. All HIV+ patients were male with a median age at diagnosis of 37 years (range 25-58 years) and median year of diagnosis of 1992 (range 1987-1998), whereas HIV- patients were evenly divided by sex with a median age at diagnosis of 65 years (range 16-90 years) and median year of diagnosis of 1992 (range 1977-2003). Among HIV-patients, 104 (86%) were deceased whereas all 54 HIV+ patients were deceased. HIV+ patients had worse prognosis compared to HIV- patients (hazard ratio (HR)=7.55, 95% confidence interval (CI) 4.34-13.12). Compared with patients with HIV-DLBCL, HIV+ patients were more likely to have ABC-DLBCL (HIV-: 46%, HIV+: 71%, p=0.0053), and less likely to have translocations of BCL2 (HIV-: 24%, HIV+: 0%, p<0.0001) and BCL6 (HIV-: 18%, HIV+: 5%, p=0.076). Among both HIV+ and HIV- patients, ABC-DLBCL was associated with adverse prognosis compared with GCB-DLBCL (HIV-: ABC HR=1.76, 95% CI 1.10-2.82, HIV+: ABC HR=2.00, 95% CI 0.93-4.33). In contrast, the presence of BCL2 and BCL6 translocations was associated with adverse prognosis in HIV- patients only (BCL2 HR=1.79, 95% CI 1.09-2.93, BCL6 HR=2.07, 95% CI 1.08-3.64). Conclusions: HIV+ and HIV- DLBCLs differ significantly with respect to key molecular characteristics, supporting biologic differences in the lymphomagenic process in the presence of HIV. The well-recognized adverse prognosis among HIV+ patients with DLBCL may be due in part to the higher proportion of ABC-DLBCLs compared to HIV- patients with DLBCL. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4490. doi:1538-7445.AM2012-4490

Spatial-temporal analysis of non-Hodgkin lymphoma in the NCI-SEER NHL case-control study.

BackgroundExploring spatial-temporal patterns of disease incidence through cluster analysis identifies areas of significantly elevated or decreased risk, providing potential clues about disease risk factors. Little is known about the etiology of non-Hodgkin lymphoma (NHL), or the latency period that might be relevant for environmental exposures, and there are no published spatial-temporal cluster studies of NHL.MethodsWe conducted a population-based case-control study of NHL in four National Cancer Institute (NCI)-Surveillance, Epidemiology, and End Results (SEER) centers: Detroit, Iowa, Los Angeles, and Seattle during 1998-2000. Using 20-year residential histories, we used generalized additive models adjusted for known risk factors to model spatially the probability that an individual had NHL and to identify clusters of elevated or decreased NHL risk. We evaluated models at five different time periods to explore the presence of clusters in a time frame of etiologic relevance.ResultsThe best model fit was for residential locations 20 years prior to diagnosis in Detroit, Iowa, and Los Angeles. We found statistically significant areas of elevated risk of NHL in three of the four study areas (Detroit, Iowa, and Los Angeles) at a lag time of 20 years. The two areas of significantly elevated risk in the Los Angeles study area were detected only at a time lag of 20 years. Clusters in Detroit and Iowa were detected at several time points.ConclusionsWe found significant spatial clusters of NHL after allowing for disease latency and residential mobility. Our results show the importance of evaluating residential histories when studying spatial patterns of cancer.

Abstract B87: Cigarette smoking, lifetime exposure to passive smoking, and the risk of non-Hodgkin lymphoma in the California Teachers Study

Abstract Background: Overall, epidemiological studies conducted to date do not support a causal relationship between smoking and non-Hodgkin lymphoma (NHL) risk. However, previous studies did not account for passive smoking in the referent group of never smokers, which may have masked subtle effects. We therefore examined the effects of cigarette smoking and passive smoking on NHL risk in the prospective California Teachers Study (CTS) cohort. Methods: The CTS collected lifetime smoking and household passive smoking exposures in 1995 and lifetime passive smoking exposures in three settings (household, workplace, and social) in 1997-1998. Multivariable-adjusted relative risks (RRs) and 95% confidence intervals (CI) were estimated by fitting Cox proportional hazards models for NHL risk with follow-up through 2007. Results: Compared to never smokers, ever smokers had a 1.11-fold elevated NHL risk (95% CI=0.94-1.30) which increased to 1.22 (95% CI=0.95-1.57) when women with household passive smoking were excluded from the reference category. Statistically significant dose-response trends were observed for lifetime cumulative smoking exposures (intensity and pack-years) when women with household passive smoking were excluded from the reference category (both p-trend=0.02). Among never smokers, NHL risk increased with increasing lifetime passive smoking exposure [RR=1.51 (95% CI=1.03-2.22) for more than 40 vs. less than or equal to 5 years, p-trend=0.03]. Both smoking and passive smoking were associated with increased risk of follicular lymphoma, but not other NHL subtypes. Conclusion: Our study provides evidence that smoking and passive smoking may play a role in NHL etiology, particularly for follicular lymphoma. Studies evaluating the effect of smoking should consider the effects of passive smoking. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B87.

Degreasing and risk of non-Hodgkin lymphoma

Objective:To investigate the relationship between selected solvent-related workplace tasks (degreasing, painting, gluing, stripping paint, staining) and risk of non-Hodgkin lymphoma (NHL).Methods:We analysed occupational data from a large population-based case-control study...

Occupational risk factors for non‐Hodgkin's lymphoma: A population‐based case–control study in Northern Germany

To identify occupational factors associated with non-Hodgkin's lymphoma (NHL). A population-based case-control study was conducted in which incident cases of high-malignancy NHL (NHL(high)), low-malignancy NHL (NHL(low)), and chronic lymphocytic leukemia (CLL) were ascertained during the period 1986-1998 among men and women aged 15-75 years residing in six German counties; controls were drawn from population registries. Occupational histories were collected and agent-specific exposures were estimated via a job-exposure-matrix. Odds ratios were estimated by conditional logistic regression. A total of 858 cases were included in these analyses. Agricultural workers [odds ratio (OR) = 2.67, 95% confidence interval (CI): 0.99, 7.21) and farmers (OR = 1.98, 95% CI: 0.98, 3.98] had elevated risk of NHL(high). Risk of NHL(low) was elevated among agricultural workers (OR = 2.46, 95% CI: 1.17, 5.16), and among blacksmiths, toolmakers, and machine tool operators (OR = 3.12, 95% CI: 1.31, 7.47). Workers in sales and construction had elevated risks of NHL(high) and NHL(low). Exposure to arsenic compounds, chlorophenols, diesel fuel, herbicides, nitrites/nitrates/nitrosamines, and organic dusts were associated with NHL(high) and NHL(low), while exhibiting little association with CLL. A positive monotonic trend in NHL(low) risk across tertiles of cumulative diesel fuel exposure was observed [P-value for test of linear trend (P) = 0.03]. These findings provide insights into several potential occupational risk factors for NHL and suggest some specific occupational agents for further investigation.

Childhood Social Environment and Risk of Non–Hodgkin Lymphoma in Adults

Better hygiene and sanitation and decreasing family size parallel the increasing incidence of non-Hodgkin lymphoma (NHL) in many populations around the world. However, whether sibship size, birth order, and crowding are related to adult NHL risk is not clear. We investigated how family structure and childhood social environment were related to the risk of NHL and NHL subtypes in a large Scandinavian population-based case control study with 6,242 participants aged 18 to 74 years. Detailed exposure information was obtained through telephone interviews. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using logistic regression, and all statistical tests were two-sided. Having four or more siblings was associated with a moderately increased risk of NHL, compared with having no siblings (OR 1.34, 95% CI 1.11-1.62, P(trend) < 0.001). Having four or more older siblings was associated with a similar risk increase (OR 1.33, 95% CI 1.12-1.59, P(trend) = 0.003) compared with being the oldest, whereas number of younger siblings was unrelated overall. The associations were independent of other environmental exposures and did not vary by country, age, or sex. High household crowding was also positively associated with risk of NHL. Results were slightly stronger for diffuse large B-cell and T-cell lymphomas than for other major NHL subtypes. Our findings add to the evidence that large sibship size, late birth order, and childhood crowding are associated with an elevated risk of NHL. Effect mechanisms may be related to early age at onset and high frequency of specific infections or total microbial exposure in childhood.

One-carbon metabolism gene polymorphisms and risk of non-Hodgkin lymphoma in Australia

Dysregulation of the one-carbon metabolic pathway, which controls nucleotide synthesis and DNA methylation, may promote lymphomagenesis. We evaluated the association between polymorphisms in one-carbon metabolism genes and risk of non-Hodgkin lymphoma (NHL) in a population-based case-control study in Australia. Cases (n = 561) and controls (n = 506) were genotyped for 14 selected single-nucleotide polymorphisms in 10 genes (CBS, FPGS, FTHFD, MTHFR, MTHFS, MTR, SHMT1, SLC19A1, TCN1, and TYMS). We also conducted a meta-analysis of all studies of Caucasian populations investigating the association between MTHFR Ex5+79C > T (a.k.a., 677C>T) and NHL risk. A global test of 13 genotypes was statistically significant for diffuse large B-cell lymphoma (DLBCL; P = 0.008), but not for follicular lymphoma (FL; P = 0.27) or all NHL (P = 0.17). The T allele at MTHFR Ex5+79 was marginally significantly associated with all NHL (OR = 1.25, 95% CI = 0.98-1.59) and DLBCL (1.36, 0.96-1.93). The T allele at TYMS Ex8+157 was associated with a reduced risk of FL (0.64, 0.46-0.91). An elevated risk of NHL was also observed among carriers of the G allele at FTHFD Ex21+31 (all NHL, 1.31, 1.02-1.69; DLBCL, 1.50, 1.05-2.14). A meta-analysis of 11 studies conducted in Caucasian populations of European origin (4,121 cases and 5,358 controls) supported an association between the MTHFR Ex5+79 T allele and increased NHL risk (additive model, P = 0.01). In conclusion, the results of this study suggest that genetic polymorphisms of one-carbon metabolism genes such as MTHFR and TYMS may influence susceptibility to NHL.

Hair dye use, genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2), and risk of non-Hodgkin lymphoma.

Several previous studies have found non-Hodgkin lymphoma (NHL) risk to be associated with hair dye use, particularly use of permanent, dark colors and use before 1980, when hair dye formulations changed. We examined NHL risk in relation to reported hair dye use among 1,321 cases and 1,057 controls from a US population-based multi-center study. DNA was extracted from blood or buccal cells to identify genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2), which encode enzymes that metabolize aromatic amine compounds found in hair dyes. Among women, 509 cases and 413 controls reported hair dye use [odds ratio (OR) = 1.2; 95% confidence interval (95% CI) = 0.9, 1.6]. Risk estimates were higher for use before 1980 than for use in 1980 or later, particularly for use of permanent, intense tone (black, dark brown, dark blonde) products (<1980-OR = 1.6; 95% CI 0.9, 2.7; >or=1980-OR = 0.6; 95% CI 0.4, 1.1). Risk estimates were increased for women who used permanent, intense tone products before 1980 if they had the rapid/intermediate NAT2 phenotype (OR = 3.3; 95% CI 1.3, 8.6) or the NAT1 10 allele (OR = 2.5; 95% CI 0.9, 7.6), but not if they were slow NAT2 acetylators (OR = 1.5; 95% CI 0.6, 3.6) or had no copies of the NAT1 10 allele (OR = 1.5; 95% CI 0.7, 3.3). NHL risk was not increased among women who began hair dye use after 1980 or among men. Our results support previous research demonstrating elevated NHL risk among women who used dark color or intense tone permanent hair dyes before 1980. We present the first evidence suggesting that this risk may differ by genetic variation in NAT1 and NAT2.

Polychlorinated Biphenyls and Non-Hodgkin Lymphoma

Several epidemiologic studies suggest that polychlorinated biphenyl (PCB) levels measured in peripheral blood or adipose tissue are related to increased risk of non-Hodgkin lymphoma (NHL) and, therefore, may be at least partially responsible for the rising incidence of NHL unrelated to HIV infection in recent decades. Case-control studies that measured PCBs in blood, adipose tissue, or household carpet dust, at the time of diagnosis, have observed elevated NHL risk associated with concentrations of either total PCBs or of specific congeners. Similar associations have been found in a number of prospective cohorts. These associations do not seem to be due to confounding by other organochlorines or by other known NHL risk factors. These results support evidence of PCB carcinogenicity from animal studies. However, interpretation of the epidemiologic evidence is limited by the wide range in measurement precision across congeners and by the moderate to high correlation among many congeners. Occupational cohort studies provide very limited support for a relationship between PCBs and NHL. In conclusion, there is mounting evidence of a relationship between certain PCBs and risk of NHL, but important questions remain, especially regarding the magnitude, timing, and causality of that relationship.

Residential Insecticide Use and Risk of Non-Hodgkin's Lymphoma

Previous studies have linked non-Hodgkin's lymphoma (NHL) with occupational exposure to insecticides, but residential use is largely unexplored. In this population-based case-control study, we examined NHL risk and use of insecticides in the home and garden. We identified NHL cases, uninfected with HIV, diagnosed between 1998 and 2000 among women and men ages 20 to 74 years in Iowa and the metropolitan areas of Los Angeles, Detroit, and Seattle. Controls were selected using random digit dialing or Medicare files. Computer-assisted personal interviews (1,321 cases and 1,057 controls) elicited data on insecticide use at each home occupied since 1970. Insecticide levels were measured in dust taken from used vacuum cleaner bags (682 cases and 513 controls). We previously reported a positive association with dichlorodiphenyldichloroethylene levels in carpet dust residues. Here, we focus on insecticides that were commonly used after 1970, the time period covered by our questionnaire. People whose homes were treated for termites had elevated NHL risk (odds ratio, 1.3; 95% confidence interval, 1.0-1.6). Risk was modestly, although not significantly, elevated in all but one study center and in all sexes and races. The elevation in risk was restricted to people whose homes were treated before the 1988 chlordane ban. There was a significant trend of increasing risk with increasing levels of alpha-chlordane residues in dust (P(trend) = 0.04) and a marginally significant trend for gamma-chlordane (P(trend) = 0.06). We found no evidence of associations for insects overall, for specific types of insects other than termites, or for elevated residues of other insecticides. We concluded that chlordane treatment of homes for termites may increase residents' NHL risk.

Dietary Determinants of One-Carbon Metabolism and the Risk of Non-Hodgkin's Lymphoma: NCI-SEER Case-Control Study, 1998–2000

The role of dietary one-carbon determinants remains largely unexplored for non-Hodgkin's lymphoma (NHL). In a population-based case-control study of non-African-American adult (aged 20-74 years) women and men from four US Surveillance, Epidemiology, and End Results study centers (Detroit, Michigan; Iowa; Los Angeles, California; and Seattle, Washington; 1998-2000), the authors examined folate; vitamins B2, B6, and B12; methionine; and a one-carbon antagonist, alcohol, in 425 incident NHL cases and 359 controls who completed a detailed food frequency questionnaire. Adjusted odds ratios and 95% confidence intervals were estimated by using unconditional logistic regression. Higher intake of one-carbon determinants from food was associated with a lower risk of NHL, but that for only vitamin B6 (highest vs. lowest quartile: odds ratio = 0.57, 95% confidence interval: 0.34, 0.95; p trend = 0.01) and methionine (odds ratio = 0.49, 95% confidence interval: 0.31, 0.76; p trend = 0.002) reached statistical significance. Folate from food was inversely associated with diffuse subtype (odds ratio = 0.47, 95% confidence interval: 0.23, 0.94; p trend = 0.03). The authors found no association between total (food plus supplement) vitamins and NHL. Nonusers of alcohol had an elevated NHL risk compared with users, and alcohol did not modify other nutrient-NHL associations. Findings suggest that one-carbon nutrients, particularly vitamin B6 and methionine, may be protective against NHL.

Medication Use and Risk of Non-Hodgkin's Lymphoma

Conflicting results from previous epidemiologic studies shed little light on whether medication use is associated with risk of non-Hodgkin's lymphoma (NHL). To investigate this question, the authors conducted a population-based case-control study in Denmark and Sweden from 1999 to 2002, including 3,055 incident NHL cases and 3,187 controls. Participants reported their past use of medications and history of particular medical conditions. Unconditional logistic regression was used to estimate multivariate odds ratios and 95% confidence intervals for the associations between medication use and risk of NHL; all statistical tests were two sided. Use of antibiotics more than 10 times during adulthood was positively associated with risk of NHL and most major NHL subtypes; when users were compared with nonusers, the odds ratio for NHL was 1.8 (95% confidence interval: 1.4, 2.3); p(trend) for total antibiotic use <0.001. In addition, high cumulative use of nonsteroidal anti-inflammatory drugs was marginally associated with elevated NHL risk. Other medications evaluated were not associated with risk of NHL or its most common subtypes. Findings suggest that inflammation, infections, susceptibility to infections, and/or use of antibiotics or nonsteroidal anti-inflammatory drugs to treat these conditions may increase the risk of NHL. However, most of the medications examined were not associated with NHL risk.