Racial Disparities in Cardiovascular and Cerebrovascular Adverse Events in Patients with Non-Hodgkin Lymphoma: A Nationwide Analysis.

Background and Objectives: Non-Hodgkin lymphoma (NHL) has the sixth-highest malignancy-related mortality in the United States (US). However, inequalities exist in access to advanced care in specific patient populations. We aim to study the racial disparities in major adverse cardiovascular and cerebrovascular events (MACCEs) in NHL patients. Materials and Methods: Using ICD-10 codes, patients with NHL were identified from the US National Inpatient Sample 2016-2019 database. Baseline characteristics, comorbidities, and MACCE outcomes were studied, and results were stratified based on the patient's race. Results: Of the 777,740 patients with a diagnosis of NHL, 74.22% (577,215) were White, 9.15% (71,180) were Black, 9.39% (73,000) were Hispanic, 3.33% (25,935) were Asian/Pacific Islander, 0.36% (2855) were Native American, and 3.54% (27,555) belonged to other races. When compared to White patients, all-cause mortality (ACM) was significantly higher in Black patients (aOR 1.27, 95% CI 1.17-1.38, p < 0.001) and in Asian/Pacific Islander patients (aOR 1.27, 95% CI 1.12-1.45, p < 0.001). Sudden cardiac death was found to have a higher aOR in all racial sub-groups as compared to White patients; however, it was statistically significant in Black patients only (aOR 1.81, 95% CI 1.52-2.16, p < 0.001). Atrial fibrillation (AF) risk was significantly lower in patients who were Black, Hispanic, and of other races compared to White patients. Acute myocardial infarction (AMI) was noted to have a statistically significantly lower aOR in Black patients (0.70, 95% CI 0.60-0.81, p < 0.001), Hispanic patients (0.69, 95% CI 0.59-0.80, p < 0.001), and patients of other races (0.57, 95% CI 0.43-0.75, p < 0.001) as compared to White patients. Conclusions: Racial disparities are found in MACCEs among NHL patients, which is likely multifactorial, highlighting the need for healthcare strategies stratified by race to mitigate the increased risk of MACCEs. Further research involving possible epigenomic influences and social determinants of health contributing to poorer outcomes in Black and Asian/Pacific Islander patients with NHL is imperative.

Associations between genetic variants in immunoregulatory genes and risk of non-Hodgkin lymphoma in a Chinese population.

We undertook a hospital-based case-control study to examine the associations between single nucleotide polymorphisms (SNPs) in selected immunoregulatory genes and non-Hodgkin lymphoma (NHL) risk in a Chinese population. One hundred and sixty-nine NHL patients diagnosed according to the World Health Organization (WHO) 2001 standard and 421 controls were recruited. Nine SNPs in three genes (IL-10, IL-1RN, and TNF-α) were selected based on predicted functions and previous study findings. Genetic association analysis was performed using the Cochran-Armitage trend test and multiple logistic regression. Four SNPs were associated with an increased risk of overall NHL: odds ratio per minor allele [ORper-minor-allele] and 95% confidence interval [CI] were 2.64 (1.75-3.98) for IL-10 rs1800893, 2.67 (1.72-4.16) for IL-1RN rs4251961, 1.80 (1.24-2.63) for TNF- α rs1800630, and 1.55 (1.02-2.37) for TNF- α rs2229094. These SNPs were also associated with an increased risk of diffuse large B-cell lymphoma (DLBCL). In addition, another SNP (TNF- α rs1041981) was associated with an increased risk of DLBCL (ORper-minor-allele=1.73, 95% CI 1.14-2.61). The findings provide evidence on the role of these immunoregulatory gene variants in NHL etiology.

Risk of nasopharyngeal carcinoma penetrates across immigrant generations: A migrant cohort study of 2.3 million Jewish Israeli adolescents.

Nasopharyngeal cancer (NPC) incidence varies widely across geographic regions and ethnic groups. We conducted a large-scale migrant cohort study to assess origin and migrant generation as predictors of NPC, controlling for possible confounders. Data on 2.3 million Jewish Israeli adolescents, who underwent a compulsory general health examination at ages 16-19 between the years 1967 and 2011 were linked to the Israel National Cancer Registry to obtain incident NPC up to 2012. Cox proportional hazards were used to model time to event. During 46.5 million person-years of follow-up, 276 incident cases were identified. Origin was a strong independent predictor of NPC with high rates for first generation North African born (adjusted HR 5.52; 95% CI 2.43-12.52; p < 0.000044) and Asian born (adjusted HR 3.79; 95% CI 1.43-10.00; p = 0.007) compared to European-born, adjusted for sex, year of birth, residential socio-economic position, years of education, rural residence, body mass index and height. The magnitude of the associations was similar in the Israeli-born of North African and Asian origin, with these second and third generation immigrants showing elevated HRs (adjusted HR 6.09; 95% CI 2.81-13.20; p = 4.72.10-6 and 3.86; 95% CI 1.77-8.41; p = 0.00067, respectively). These findings suggest a strong genetic predisposition and/or efficient cultural transmission of environmental exposures in the etiology of NPC.

Genetic characteristics of non-Hodgkin lymphoma in ethnic Uighur people, and their clinical significance.

The incidence of non-Hodgkin lymphoma (NHL) in China is increasing and is attracting attention as a topic of research. The percentage of NHL cases in ethnic Uighur people is also gradually increasing. We therefore recruited Uighur people with NHL to investigate the correlation between genetic alternations and clinical/pathological features in an attempt to determine their clinical significance. A total of 60 NHL patients were recruited from our hospital for a microscopic examination of their tumor cell morphology. Further analysis of chromosome karyotypes revealed the relationship between genetic alternations and clinical/pathological features. Microscopic examination revealed increased numbers of tumor cells with altered morphology. The recruited patients all exhibited abnormal karyotypes. Chromosomal breakages were detected at 14q32, 18q21, 6q21-25, +3, +, +18, and short tandem repeat 17 (str17) in 18.3, 25, 25, 18.3, 15, and 21.7% of patients, respectively. Karyotype change was not related to age, gender, performance status score, or pathological type (P > 0.05), but was correlated with clinical stage, average lactate dehydrogenase (LDH) level, extra-lymphatic metastasis, median survival time, and efficacy of radio- or chemotherapy (P < 0.05). Independent risk factors for genetic change in Uighur NHL patients included clinical stage, average LDH level, extra-lymphatic metastasis, median survival time, and efficacy of radio- or chemotherapy (P < 0.05). Uighur NHL patients exhibited genetic changes including t(14:18), 6q21-25, +3, +7, +18, and str17. Clinical stage, average LDH level, extra-lymphatic metastasis, median survival time, and efficacy of radio- or chemotherapy were all independent risk factors for NHL.

Non-Hodgkin lymphoma in Southern Africa: review of 487 cases from The International Non-Hodgkin Lymphoma Classification Project.

Comparative data on the distribution of non-Hodgkin lymphoma (NHL) subtypes in Southern Africa (SAF) is scarce. In this study, five expert haematopathologists classified 487 consecutive cases of NHL from SAF using the World Health Organization classification, and compared the results to North America (NA) and Western Europe (WEU). Southern Africa had a significantly lower proportion of low-grade (LG) B-NHL (34·3%) and a higher proportion of high-grade (HG) B-NHL (51·5%) compared to WEU (54·5% and 36·4%) and NA (56·1% and 34·3%). High-grade Burkitt-like lymphoma was significantly more common in SAF (8·2%) than in WEU (2·4%) and NA (2·5%), most likely due to human immunodeficiency virus infection. When SAF patients were divided by race, whites had a significantly higher frequency of LG B-NHL (60·4%) and a lower frequency of HG B-NHL (32·7%) compared to blacks (22·5% and 62·6%), whereas the other races were intermediate. Whites and other races had a significantly higher frequency of follicular lymphoma and a lower frequency of Burkitt-like lymphoma compared to blacks. The median ages of whites with LG B-NHL, HG B-NHL and T-NHL (64, 56 and 67 years) were significantly higher than those of blacks (55, 41 and 34 years). Epidemiological studies are needed to better understand these differences.

Immune reconstitution inflammatory syndrome versus non-immune reconstitution inflammatory syndrome lymphoma in HIV patients on antiretroviral therapy.

Little is known about differences between immune reconstitution inflammatory syndrome (IRIS) and non-IRIS lymphoma in HIV patients on antiretroviral therapy (ART). The aim of this study was to describe the characteristics of IRIS and non-IRIS lymphoma in Korean HIV-positive patients on ART compared with lymphoma in those off ART. Of 1490 patients, 41 (3%) had lymphoma. Of these, 27 cases (66%) were classified as lymphoma off ART, eight as IRIS lymphoma, and six as non-IRIS lymphoma on ART. Hodgkin lymphoma was significantly more common among patients with non-IRIS lymphoma on ART than among those with lymphoma off ART (P = 0.005), whereas there was no Hodgkin lymphoma among IRIS lymphoma. Stage IV lymphoma was significantly rarer in non-IRIS lymphoma on ART than in lymphoma off ART (P = 0.007). Non-IRIS lymphoma on ART tends to have a better survival rate than lymphoma off ART (Kaplan-Meier survival analysis, P = 0.167), while IRIS lymphoma exhibited a survival rate similar to lymphoma off ART (P = 0.618). In Korean HIV-positive patients, there were significantly more cases of Hodgkin lymphoma of a less advanced stage in non-IRIS lymphoma on ART than in lymphoma off ART, in contrast to IRIS lymphoma.

Nutritional factors and non-Hodgkin lymphoma survival in an ethnically diverse population: the Multiethnic Cohort.

BACKGROUND/OBJECTIVES: To understand the possible effect of modifiable health behaviors on the prognosis of the increasing number of non-Hodgkin lymphoma (NHL) survivors, we examined the pre-diagnostic intake of major food groups with all-cause and NHL-specific survival in the Multiethnic Cohort (MEC). SUBJECTS/METHODS: This analysis included 2339 participants free of NHL at cohort entry and diagnosed with NHL as identified by cancer registries during follow-up. Deaths were ascertained through routine linkages to state and national death registries. Cox proportional hazards regression was applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and NHL-specific mortality according to pre-diagnostic intake of vegetables, fruits, red meat, processed meat, fish, legumes, dietary fiber, dairy products and soy foods assessed by food frequency questionnaire. RESULTS: The mean age at diagnosis was 71.8±8.5 years. During 4.5±4.1 years of follow-up, 1348 deaths, including 903 NHL-specific deaths, occurred. In multivariable models, dairy intake was associated with higher all-cause mortality (highest vs lowest tertile: HR=1.14, 95% CI 1.00-1.31, Ptrend=0.03) and NHL-specific (HR=1.16, 95% CI 0.98-1.37) mortality. Legume intake above the lowest tertile was related to significant 13-16% lower all-cause and NHL-specific mortality, whereas red meat and fish intake in the intermediate tertiles was associated with lower NHL-specific mortality. No association with survival was detected for the other food groups. CONCLUSIONS: These data suggest that pre-diagnostic dietary intake may not appreciably contribute to NHL survival, although the higher mortality for dairy products and the better prognosis associated with legumes agree with known biologic effects of these foods.

HLA Polymorphism in Algerian Children With Lymphomas.

BACKGROUND: Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) are the 2 types of lymphoma that represent the third most common childhood malignancy. Multiple etiological factors are involved in lymphoma pathogenesis, including viral infection, immune deficiencies, environmental agents, and genetic factors. Strong arguments supporting a genetic linkage between the susceptibility to lymphomas and human leukocyte antigens (HLA) are reported and give an idea about susceptibility or protection from the disease. METHODS: Seventy-one cases were included in this study: 36 cases of non-Hodgkin lymphoma and 35 patients with Hodgkin lymphoma. Their ages ranged from 4 to 18 years. The control group consisted of 70 unrelated healthy individuals, with a mean age of 5 to 17 years. The genotype of HLA-A, HLA-B, HLA-DR, and HLA-DQ alleles was typed by means of PCR sequence-specific priming. RESULTS: HLA-B*18, HLA-DRB1*03, *07, and HLA-DQB1*02 were significantly increased in patients with lymphomas when compared with controls, whereas HLA-DRB1*13 and DQB1*03 were significantly decreased when compared with controls. CONCLUSIONS: These results indicate that HLA-B*18, DRB1*03, *07, and DQB1*02 may contribute to lymphoma susceptibility, whereas HLA-DRB1*13 and DQB1*03 may confer protection to lymphoma in the Algerian population.

US trends in survival disparities among adolescents and young adults with non-Hodgkin lymphoma.

PURPOSE: Improvement in US survival rates among adolescents and young adults (AYAs, ages 15 through 39 years inclusive) diagnosed with non-Hodgkin lymphoma (NHL) has been documented over the last two decades. We examined national trends in survival disparities for AYAs with NHL by race/ethnicity and socioeconomic status (SES, county-level poverty) to further understand NHL and to begin monitoring health outcome disparities for this disease. METHODS: Surveillance Epidemiology and End Results data were used to calculate 5-year relative survival rates of AYAs diagnosed with NHL from 1992 to 2007 and followed through 2011. Absolute and relative disparities were computed using HD*Calc. Whether a significant linear trend was present was evaluated using Joinpoint. Analyses were replicated after excluding individuals with known HIV infection. RESULTS: The study sample included 9,573 total and 7,121 non-HIV cases of NHL. Five-year survival rates improved for all groups over time. Significant decreases were found in absolute disparities for race/ethnicity (non-HIV), in relative disparities for SES (total) and race/ethnicity (total and non-HIV) (all p < 0.05). Survival rates of non-Hispanic Blacks and Hispanics remained below than those of non-Hispanic Whites throughout the time period. CONCLUSION: Absolute and relative disparities in 5-year survival narrowed for AYAs with NHL over the time period. To continue to promote this trend, future research should investigate factors, particularly diagnostic delays and barriers to care, which continue to contribute to SES and racial/ethnic differences in survival. These factors may be particularly relevant to identify given the recent Affordable Care Act, which is designed to increase access to medical services, particularly for young adults.

Primary Bone Lymphoma: A Clinical Analysis of 17 Patients in a Single Institution.

Primary bone lymphoma (PBL) comprises less than 1% of all malignant lymphomas. Because few studies of PBL have been conducted in Japan, the characteristics of Japanese patients with PBL have not been fully elucidated. We retrospectively analyzed 17 patients diagnosed with PBL at our institution between 2001 and 2011. Median patient age was 60 years. Eleven patients had diffuse large B-cell lymphoma and 2 patients had T-cell lymphoma histology. The spine was the most frequently involved site at the time of presentation. There were 11 patients with stage IV disease and 11 patients with high or high-intermediate risk according to the International Prognostic Index (IPI). Thirteen patients achieved complete response (CR) after initial treatment. At a median follow-up of 31 months, the 3-year overall survival (OS) and progression free survival were 63.5 and 49.9%, respectively. Localized disease, low or low-intermediate IPI, and CR after initial treatment were associated with a good outcome in patients with PBL and significantly associated with a better OS. Spine involvement and T/NK-cell phenotype are more frequent in Japanese than in Caucasian patients with PBL.

LEP and LEPR polymorphisms in non-Hodgkin lymphoma risk: a systematic review and pooled analysis.

PURPOSE: The purpose of this systematic meta-analysis was to evaluate the association between leptin (LEP) and leptin receptor (LEPR) gene polymorphisms and non-Hodgkin lymphoma (NHL) risk. METHODS: All studies published up to July 2014 on the association between LEP and LEPR polymorphisms and NHL risk were identified by searching PubMed, Web of Science, EMBASE, and Google Scholar. Odds ratios (ORs) with 95% confidence intervals (CIs) for LEP and LEPR polymorphisms and NHL were calculated with fixed-effects and random-effects models. RESULTS: LEP G2528A polymorphism was associated with increased, yet not statistically significant risk of NHL (homozygote comparison, OR=1.27, 95% CI=1.01-1.60, p=0.63; heterozygote comparison, OR=1.13, 95% CI=0.86-1.49, p=0.14; dominant model, OR=1.18, 95% CI=0.99-1.41, p=0.21; recessive model, OR=1.18, 95% CI=0.97-1.43, p=0.78; additive model, OR=1.14, 95% CI=1.01-1.28, p=0.52). Significant decrease of NHL risk was found in LEP A19G polymorphism, while no links were detected with the LEPR polymorphisms studied. In subgroup analysis, the pooled results showed that LEP A19G polymorphism was associated with decreased risk of follicular lymphoma (FL) (homozygote comparison, OR=0.56, 95% CI=0.37-0.85, p=0.69). However, no evidence of a significant association was observed in diffuse large B-cell lymphoma (DLBCL) for variant genotypes of all single nucleotide polymorphisms (SNPs). CONCLUSIONS: LEP G2548A polymorphism contributes to NHL susceptibility. Also, our results provide evidence that LEP A19G polymorphism is associated with decreased risk of NHL, especially in FL. Further large-scale and well-designed studies are needed to confirm this association.

Survival Differences by Race/Ethnicity and Neighborhood Socioeconomic Status in Adolescents and Young Adults Diagnosed with Non-Hodgkin Lymphoma.

PURPOSE: Lymphoid malignancies are among the most common cancers diagnosed in adolescents and young adults (AYAs). However, little is known about the factors affecting survival in AYAs with non-Hodgkin lymphoma (NHL). We evaluated if survival differs by race/ethnicity and neighborhood socioeconomic status in AYAs with NHL. METHODS: AYAs aged 15-39 diagnosed with incident NHL during 1990-2010 at Kaiser Permanente Southern California (KPSC), a large managed care organization, were identified. Demographic information and cancer characteristics were obtained from KPSC's cancer registry. Mortality data were obtained from California and national death files. Patients were followed from NHL diagnosis to 5 years postdiagnosis or 12/31/2012, whichever came first. Multivariable Cox model was used to evaluate the association between race/ethnicity, neighborhood income/education level, and mortality, adjusting for age, gender, stage, year of diagnosis, and histology subtype. RESULTS: A total of 718 AYAs with NHL were included (mean age at diagnosis: 31 years); 45% were non-Hispanic white, 10% were African American, 36% were Hispanic, and 8% were Asian/Pacific Islander. Overall 5-year mortality was 30%. Compared to non-Hispanic whites, Asians/Pacific Islanders had increased 5-year mortality (hazard ratio=1.95, 95% confidence interval: 0.93-4.07). No significant increase in mortality was found for Hispanics or African Americans. Lower neighborhood income but not education level was associated with worse overall survival. CONCLUSION: A survival disparity for Asians/Pacific Islanders and low-income neighborhoods was observed in AYAs with NHL despite relatively equal access to care. These results call for studies to further understand mechanisms underlying the inferior outcomes among disadvantaged subgroups.

Polymorphic variation of inflammation-related genes and risk of non-Hodgkin lymphoma for Uygur and Han Chinese in Xinjiang.

Polymorphisms of inflammation-related genes have been found to be associated with non-Hodgkin lymphoma (NHL) or some of its subtypes, but only a few relevant data have been reported in China. In this study, the Snapshot method was used to assess genetic variation; a total of 14 single nucleotide polymorphisms (SNPs) for 6 inflammatory factors in 157 NHL cases (64 Uygur ethnic subjects, 93 Han Chinese) and 435 controls (231 Uygur and 204 Han Chinese) were studied from the Xinjiang province of China. Haplotype distribution was estimated using PHASE 2.3 software. Statistical differences in the genotype and haplotype frequencies between case and control groups were also considered and estimated. For the Han population, the geneotype distributions for TNF- αrs1800629, TNF-αrs1800630, IL-6 rs1800795, IL-6 rs1800797, NF-KB1 rs1585215 and TLR-4 rs4986790 showed significant differences between the case and control groups (p<0.05). The TNF-α gene frequencies of ACG and CCA haplotypes in the cases were higher than in the controls (OR=2.45, 95% CI: 1.55-3.89, p=0.0002, OR=2.53, 95% CI: 1.10-5.80, p=0.029, respectively), and the same findings were detected for TNF-ß gene CA haplotype (OR=1.87, 95% CI: 1.21-2.90, p=0.0054). However, for the Uygur population, no such significant differences were detected within the gene-type distribution of the 14 SNPs. The TNF-α gene frequency of the CCA haplotype between the two groups (OR=1.98, 95% CI: 1.11-3.51, p=0.021) revealed a statistically significant difference. Our results showed that polymorphic variations of inflammation-related genes could be important to the NHL etiology of the Han population, and that these may only have limited influence on the Uygur population.

Comprehensive assessment of associations between ERCC2 Lys751Gln/Asp312Asn polymorphisms and risk of non- Hodgkin lymphoma.

BACKGROUND: Excision repair crossing-complementing group 2 (ERCC2), also called xeroderma pigmentosum complementary group D (XPD), plays a crucial role in the nucleotide excision repair (NER) pathway. Previous epidemiological studies have reported associations between ERCC2 polymorphisms and non-Hodgkin lymphoma (NHL) risk, but the results have remained controversial. MATERIALS AND METHODS: We conducted this meta- analysis based on eligible case-control studies to investigate the role of two ERCC2 polymorphisms (Lys751Gln and Asp312Asn) in determining susceptibility to NHL. Ten case-control studies from several electronic databases were included in our study up to August 14, 2014. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects models to estimate the association strength. RESULTS: The combined results based on all studies did not show any association between Lys751Gln/Asp312Asn polymorphisms and NHL risk for all genetic models. Stratified analyses by histological subtype and ethnicity did not indicate any significant association between Lys751Gln polymorphism and NHL risk. However, a significant reduced risk of NHL was found among population-based studies (Lys/Gln versus Lys/Lys: OR=0.87, 95% CI=0.77-0.99, P=0.037) but not hospital-based studies. As for Asp312Asn polymorphism, there was no evidence for the association between this polymorphism and the risk of NHL in all subgroup analyses. CONCLUSIONS: This meta-analysis suggests that there may be no association between Lys751Gln/Asp312Asn polymorphism and the risk of NHL and its two subtypes, whereas ERCC2 Lys751Gln heterozygote genotype may provide protective effects against the risk of NHL in population-based studies. Therefore, large-scale and well-designed studies are needed to clarify the effects of haplotypes, gene-gene, and gene-environment interactions on these polymorphisms and the risk of NHL and its different histological subtypes in an ethnicity specific population.

Obesity and non-Hodgkin lymphoma survival in an ethnically diverse population: the Multiethnic Cohort study.

PURPOSE: Obesity increases mortality for several malignancies, but for non-Hodgkin lymphoma (NHL), the association between body mass index (BMI) and survival is unclear. We examined the association of pre-diagnostic BMI with overall and NHL-specific survival in the multiethnic cohort (MEC) study of African Americans, Native Hawaiians, Japanese Americans, Latinos, and Caucasians. METHODS: MEC participants free of NHL at cohort entry and diagnosed with NHL during follow-up were included in the analyses (n = 1,331). BMI was based on self-reported weight and height at cohort entry and after 6.1 years of cohort entry. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95 % confidence intervals (CI) with BMI as time-varying exposure in relation to all-cause and NHL-specific mortality while adjusting for known confounders. RESULTS: The mean age at NHL diagnosis was 70.5 (range 45-89) years. After a mean follow-up of 4.3 ± 3.5 years, 667 deaths including 450 NHL-specific deaths occurred. In multivariable models, obese patients (BMI ≥30.0 kg/m(2)) had higher all-cause (HR 1.46, 95 % CI 1.13-1.87) and NHL-specific (HR 1.77, 95 % CI 1.30-2.41) mortality compared with patients with high-normal BMI (22.5-24.9 kg/m(2)). For overweight patients (BMI = 25.0-29.9 kg/m(2)), the respective HRs were 1.21 (95 % CI 0.99-1.49) and 1.36 (95 % CI 1.06-1.75). Cases with low-normal BMI (<22.5 kg/m(2)) experienced a significant 45 % higher all-cause and a 40 % higher NHL-specific mortality. After stratification by NHL type, the adverse effect of BMI was stronger for chronic lymphocytic leukemia/small lymphocytic lymphoma than for diffuse large B cell lymphoma and follicular lymphoma. CONCLUSIONS: Pre-diagnostic BMI may be a suitable prognostic marker for NHL patients.

The +252A/G polymorphism in the Lymphotoxin-α gene and the risk of non-Hodgkin lymphoma: a meta-analysis.

BACKGROUND AND OBJECTIVES: Many studies have shown that the +252A/G polymorphism in the lymphotoxin-α gene is implicated in susceptibility to non-Hodgkin lymphoma but with considerable variance of results. This study aimed to clarify the overall association between the +252A/G polymorphism in the lymphotoxin-α gene and non-Hodgkin lymphoma (NHL) risk by performing a meta-analysis. MATERIALS AND METHODS: The Pubmed and Embase databases were searched for all studies relating to lymphotoxin-α +252A/G gene polymorphism and NHL risk. Data were retrieved and statistical analyses were performed using the Revman 5.1 and STATA 12.0 software. RESULTS: Fourteen case-control studies with 25,098 subjects were included. There was no significant association between lymphotoxin-α +252A/G gene polymorphism and the risk of NHL in the all-combined analysis (OR = 1.08, 95%CI: 0.98-1.19 for GG+GA vs. AA; OR = 1.05, 95%CI: 0.95-1.25 for GG vs. GA+AA). In a subgroup analysis by ethnicity, increased NHL risk was found in North Americans (OR = 1.21, 95%CI: 1.05-1.39 for GG+GA vs. AA), no significant association with NHL risk was identified in Asians or Europeans; In a subgroup analysis by NHL subtype, a significantly increased risk was identified in diffuse large B cell lymphoma patients (OR = 1.20 95%CI: 1.11-1.29 for GG+GA vs. AA), but not for follicular lymphoma. CONCLUSIONS: This meta-analysis suggested that the lymphotoxin-α +252A/G gene polymorphism is a risk factor for NHL in North Americans, and this polymorphism may contribute to diffuse large B cell lymphoma susceptibility. Future studies that include different types of NHL and ethnicities are needed to support and extend these observations.

EZH2 mutations in follicular lymphoma from different ethnic groups and associated gene expression alterations.

PURPOSE: Gain-of-function mutations of enhancer of Zeste homolog 2 (EZH2) occur frequently in diffuse large B-cell lymphomas and in follicular lymphomas. However, the frequency of EZH2 mutation in Chinese follicular lymphomas and the potential targets affected by this mutation are unknown. EXPERIMENTAL DESIGN: We determined EZH2 codon 641 mutations in Chinese follicular lymphomas (n = 124) and compared them with Western follicular lymphomas (n = 70) using a sensitive pyrosequencing assay. Gene expression profiling (GEP) was performed to determine differential gene expression between the mutated versus unmutated subgroups, and selected genes were validated using immunohistochemistry. RESULTS: Our results showed similar frequencies of EZH2 codon 641 mutations in Chinese and Western follicular lymphoma cohorts (16.9% vs. 18.6%, χ(2) test, P = 0.773), including all five reported mutation variants. We observed significant association of EZH2 mutation with low morphologic grade follicular lymphomas (grade 1-2, 23.6% vs. grade 3, 7.7%, χ(2) test, P = 0.02). EZH2 mutations also showed significant association with BCL2 rearrangement in the Chinese cohort (26.8% vs. 8.8%, χ(2) test, P = 0.008) and combined cohorts (26.3% vs. 9.1%, χ(2) test, P = 0.002). GEP analysis identified several genes, including TCF4, FOXP1, TCL1A, BIK, and RASSF6P, with significantly lower mRNA expression (P < 0.01) in mutated cases, and the potential target TCL1A showed consistent results at the protein level. CONCLUSION: Similar prevalence of EZH2 mutation in two ethnic groups suggests shared pathogenetic mechanisms. The much lower frequency of EZH2 mutation in cases without BCL2 translocation suggests a different pattern of evolution of this subtype of follicular lymphoma. GEP studies showed a set of differentially expressed genes and suggested that EZH2 mutation may help to lock the tumor cells at the germinal center stage of differentiation.

Prediagnostic serum tocopherol levels and the risk of non-hodgkin lymphoma: the multiethnic cohort.

BACKGROUND: Compromised immunity and chronic inflammation are thought to contribute to the development of non-Hodgkin lymphoma (NHL). Because tocopherols protect cells through antioxidant mechanisms, they may play a role in NHL etiology. METHODS: This nested case-control study within the Multiethnic Cohort examined the association of prediagnostic serum tocopherols levels measured in 271 NHL cases and 538 matched controls by high-pressure liquid chromatography/photodiode array detection with NHL risk. Conditional logistic regression was used to calculate ORs and 95% confidence intervals (CI). RESULTS: We observed U-shaped associations with NHL for total and α-tocopherols [Ptrend < 0.01 for polynomial terms (3 df)]. The ORs (95% CI) for total tocopherols, which consisted primarily of α-tocopherol, were 0.41 (0.25-0.68), 0.52 (0.32-0.85), 0.39 (0.23-0.65), and 0.78 (0.47-1.29) for the second to fifth quintiles as compared with the first. The risk estimates were similar for α-tocopherol but nonsignificant for ß- and γ-tocopherol combined and for γ-tocopherol. Adjustment for serum lipids strengthened the nonlinear associations for total and α-tocopherols. Serum total tocopherol levels were higher for vitamin E supplement users at cohort entry than nonusers (21.32 ± 9.04 vs. 17.72 ± 7.43 µg/mL; P < 0.0001), but supplement use was not associated with NHL risk. No heterogeneity in risk estimates was detected by sex, ethnicity, vitamin E supplement use, or NHL subtype. CONCLUSIONS: Circulating tocopherols, at levels likely reflecting adequate dietary intakes, may be protective against NHL, whereas higher intakes from supplementation may not be beneficial. IMPACT: The association between serum tocopherol levels and NHL risk provides possible new insights into the etiology of NHL.

Risk of genome-wide association study-identified genetic variants for non-Hodgkin lymphoma in a Chinese population.

Recent genome-wide association studies have identified 15 single nucleotide polymorphisms (SNPs) associated with non-Hodgkin lymphoma (NHL) and its subtypes. Because the incidence and subtype portion of NHL between the Chinese population and Caucasian populations are substantially different, we assessed the associations of these SNPs with NHL risk in a case-control study consisting of 792 cases and 1542 controls derived from the Chinese population. Odds ratios (OR) and 95% confidence intervals (CI) were computed by logistic regression. False-positive report probability was also assessed for significant findings. We found that the allele frequencies of the 15 SNPs in our study population significantly differed from those in Caucasian populations, with rs13397985, rs735665 and rs11083846 being extremely rare in Chinese. Only two variants (rs872071 in IRF4 and rs2647012 in HLA class II) were significantly associated with NHL risk in Chinese, with the ORs of 1.20 (95% CI, 1.05-1.38; P = 0.009) and 1.20 (95% CI, 1.03-1.39; P = 0.018) for per allele of rs872071 and rs2647012, respectively, calculated using an additive model. These results indicate a substantial different genetic background for susceptibility to NHL among the different ethnic populations.