Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence supporting the contribution of oxidative stress to key pathways in cancer, such as inflammation and DNA damage, continues to mount. We investigated variations within genes mediating oxidative stress to determine whether they alter risk for non-Hodgkin lymphoma (NHL). Thirteen single nucleotide polymorphisms (SNPs) from 10 oxidative stress genes (AKR1A1, AKR1C1, CYBA, GPX, MPO, NOS2A, NOS3, OGG1, PPARG and SOD2) were genotyped in 1172 NHL cases and 982 population-based controls from a USA multicenter case-control study. For NHL and five subtypes (diffuse large B-cell, follicular, marginal zone, small lymphocytic and T-cell), SNP associations were calculated. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for sex, age (<45, 45-64, 65+ years), race (white, black, other) and study site. Overall, the oxidative stress pathway was associated significantly with the B-cell NHL subtype, diffuse large B-cell lymphoma (DLBCL) (global P-value=0.003). Specifically, for nitric oxide synthase (NOS2A Ser608Leu, rs2297518) Leu/Leu homozygotes, there was a 2-fold risk increase for NHL (OR=2.2, 95% CI=1.1-4.4) (referent=Ser/Ser and Ser/Leu). This risk increase was consistent by cell lineage (B- and T-cell NHL) and pronounced for the two most common subtypes, diffuse large B-cell (OR=3.4, 95% CI=1.5-7.8) and follicular lymphoma (OR=2.6, 95% CI=1.0-6.8). In an analysis of manganese superoxide dismutase (SOD2 Val16Ala, rs1799725) Ala/Ala homozygotes, we observed moderately increased risks for B-cell lymphomas (OR=1.3, 95% CI=1.0-1.6; referent=Val/Val and Val/Ala) that was consistent across the B-cell subtypes. Genetic variations that result in an increased generation of reactive oxygen species appear to increase risk for NHL and its major subtypes, particularly DLBCL. Independent replication of our findings are warranted and further evaluation of oxidative stress in the context of inflammation, DNA repair and the induction of the NF-kappaB pathway may further reveal important clues for lymphomagenesis.
Carcinogenesis 2006 Sep
PMID:Polymorphisms in oxidative stress genes and risk for non-Hodgkin lymphoma. 1654 47

Recent findings suggest that genetic polymorphisms in TNF and IL10 are associated with an increased risk of non-Hodgkin lymphoma (NHL), particularly for diffuse large B-cell lymphoma (DLBCL). To further investigate the contribution of common genetic variation in key cytokine and innate immunity genes to the etiology of NHL, we genotyped participants in a case-control study of NHL conducted in Australia (545 cases, 498 controls). We investigated 36 single nucleotide polymorphisms in IL10, TNF and 21 other immune function genes. We observed an elevated risk of DLBCL with the IL10 -3575T>A polymorphism [TA genotype: odds ratio (OR)=1.32, 95% confidence interval (CI)=0.86-2.02; AA, OR=1.84, 95% CI=1.10-3.08; trend test, P=0.02]. Our most noteworthy TNF finding was an association between -857C>T and a decreased risk of NHL (CT or TT, OR=0.59, 95% CI=0.42-0.84, P=0.003) and particularly follicular lymphoma (OR=0.40, 95% CI=0.23-0.68, P=0.0009). Additionally, TNF -863C>A was associated with an elevated risk of DLBCL (CA, OR=1.45, 95% CI=0.95-2.21; AA, OR=2.06, 95% CI=0.88-4.83; trend test, P=0.02). Our findings offer further evidence that variation in the IL10 and TNF loci influences NHL risk. Additional studies are needed to clarify the genetic and biologic basis for these relationships.
Carcinogenesis 2007 Mar
PMID:Polymorphisms in immune function genes and risk of non-Hodgkin lymphoma: findings from the New South Wales non-Hodgkin Lymphoma Study. 1705 5

To date, the biological significance of breast cancer resistance protein (BCRP) G34A and C421A polymorphisms is largely unknown. Analysis of these two polymorphisms in 156 diffuse large B-cell lymphoma (DLBCL) patients and 376 control subjects revealed an increased risk of DLBCL associated with variant BCRP 421 genotypes (CA and AA), when compared with the wild-type CC genotype [odds ratio = 1.49, 95% confidence interval (CI) 1.02-2.17, P = 0.042]. Moreover, the increased risk was more evident in younger patients (<or=50 years, odds ratio = 2.14, 95% CI 1.25-3.68, P = 0.006). Further evaluation for the association of these polymorphisms with overall survival of DLBCL showed that patients with 34AA alleles displayed worse survival compared with those carrying GG/GA genotypes [hazard ratio (HR) = 3.69, 95% CI 1.56-8.71, P = 0.001]. Significant association between 421CC genotypes and poorer survival of DLBCL was observed in patients younger at diagnosis (<or=50 years, HR = 5.80, 95% CI 1.16-28.90, P = 0.015) or with bulky tumor (HR = 4.36, 95% CI 1.04-18.31, P = 0.027). Furthermore, we found the combined effects of BCRP G34A and C421A on the overall survival. Compared with patients carrying BCRP 34(GG + GA)421(AA + CA) genotype, the individual with 34AA421CC displayed the worst survival (HR = 7.55, 95% CI 2.36-24.17, P = 0.001), while those with 34(GG + GA)421CC and 34AA421(AA + CA) combinations showed the intermediate survival. These results suggest that the BCRP G34A and C421A polymorphisms are associated with the risk and survival of DLBCL. Our finding warrants further investigations on the association of BCRP polymorphisms with susceptibility and clinical outcome of cancer.
Carcinogenesis 2007 Aug
PMID:BCRP gene polymorphisms are associated with susceptibility and survival of diffuse large B-cell lymphoma. 1749 54

Tumor protein 53 (TP53), a transcriptional factor, induces expression of the B-cell lymphoma 2-associated X protein (BAX) gene by directly binding to the TP53-binding element in the BAX promoter but inhibits B-cell lymphoma 2 (BCL2) promoter-driven transcription through a responsive region in the BCL2 promoter. Therefore, we hypothesized that single-nucleotide polymorphisms (SNPs) of BAX and BCL2 promoters and the TP53 codon 72 SNP may jointly contribute to cancer risk. We tested this hypothesis in a hospital-based case-control study of 814 patients with squamous cell carcinoma of the head and neck (SCCHN) and 934 cancer-free controls in a US non-Hispanic white population. While there was no evidence of associations between BAX (-248 G>A), BCL2 (-938 C>A) or TP53 codon 72 SNPs and SCCHN risk in single-locus analyses, further analyses showed that, among TP53 heterozygotes after adjustment for age, sex and smoking and alcohol status, the BAX AA genotype was associated with an elevated risk of SCCHN [odds ratio (OR) = 6.60, 95% confidence interval (CI) = 1.38-31.50 compared with the BAX GG genotype or OR = 6.58, 95% CI = 1.38-31.49 compared with the combined genotypes (GG + AG)], whereas BCL2 A variant genotypes were associated with a decreased risk of SCCHN (adjusted OR = 0.68, 95% CI = 0.47-0.98 for CA vs CC and OR = 0.67, 95% CI = 0.48-0.95 for AA vs CA+CC). These altered risks appeared to be consistent with the roles of the anti-apoptotic BCL2 and the pro-apoptotic BAX. Our data suggest that the risk of SCCHN may be associated with these two SNPs of BAX and BCL2 promoter regions, particularly among TP53 heterozygotes. Larger studies are needed to validate these findings.
Carcinogenesis 2007 Sep
PMID:Single-nucleotide polymorphisms at the TP53-binding or responsive promoter regions of BAX and BCL2 genes and risk of squamous cell carcinoma of the head and neck. 1769 66

Recently, it has been found that inappropriate expression of microRNAs (miRNAs) is strongly associated with carcinogenesis. In this study, we demonstrated that the expression of miRNAs (miRs) -143 and -145, the levels of which were previously shown to be reduced in colon cancers and various kinds of established cancer cell lines, was also decreased in most of the B-cell malignancies examined, including chronic lymphocytic leukemias (CLL), B-cell lymphomas, Epstein-Barr virus (EBV)-transformed B-cell lines, and Burkitt lymphoma cell lines. All samples from 13 CLL patients and eight of nine B-cell lymphoma ones tested exhibited an extremely low expression of miRs-143 and -145. The expression levels of miRs-143 and -145 were consistently low in human Burkitt lymphoma cell lines and were inversely associated with the cell proliferation observed in the EBV-transformed B-cell lines. Moreover, the introduction of either precursor or mature miR-143 and -145 into Raji cells resulted in a significant growth inhibition that occurred in a dose-dependent manner and the target gene of miRNA-143 was determined to be ERK5, as previously reported in human colon cancer DLD-1 cells. Taken together, these findings suggest that miRs-143 and -145 may be useful as biomarkers that differentiate B-cell malignant cells from normal cells and contribute to carcinogenesis in B-cell malignancies by a newly defined mechanism.
 ...
PMID:Downregulation of microRNAs-143 and -145 in B-cell malignancies. 1789 14

Hepatitis C virus (HCV) has been recently recognized as a potential cause of B-cell lymphoma. Both chronic hepatitis B and C with or without cirrhosis represent major preneoplastic conditions, and the majority of hepatocellular carcinomas arise in these pathological settings. According to the aneuploidy-cancer theory, carcinogenesis is initiated by random aneuploidy, which is either induced by carcinogens or arises spontaneously. The aim of this study was to evaluate random aneuploidy rate in HCV patients during chronic infection and remission (past infection eradicated), compared with non-Hodgkin lymphoma (NHL) patients and healthy controls. To determine random aneuploidy, we applied the FISH technique with probes for chromosomes 9 and 18. Significantly higher random aneuploidy rate was found in the HCV-infected and lymphoma patients than in the control group; the past HCV group in remission had intermediate rates, between those of the control group and the chronically infected patients. Patients who have eradicated HCV infection may nonetheless carry higher risk for future malignancy and therefore need long-term follow-up.
 ...
PMID:Random aneuploidy in chronic hepatitis C patients. 1806 28

Anti-apoptotic factors including IAP-survivin and bcl-2 are involved in carcinogenesis and predict for disease outcome for patients with cancer. We used RT-PCR and specific primers to generate two recombinant IAP-survivin proteins; one encoding for the full-length protein and the second comprising the survivin sequence incorporating amino acids 98 to 142. Both proteins were used to immunize mice and as capture antigens to screen NS1/immune splenocyte hybridoma supernatants for anti-survivin antibody in ELISA assays. The antibody designated F2-9C3 was most effective and reacted with both recombinant proteins and with the native protein present in lysates of A549 (lung carcinoma) and Jurkat cells in Western blots, immunoprecipitation and formalin-fixed tissue sections. Immunohistochemical staining of normal and neoplastic tissues showed association of the F2-9C3 antibody with the mitotic spindles. Expression of survivin was not detected elsewhere in sections of normal tissue while all neoplastic tissues examined, including those from patients with diffuse large B-cell lymphoma (DLBCL), showed significant expression of survivin. The intensity and localization of staining in these tumours varied and was observed in cytoplasm and/or nuclei. High nuclear expression of survivin predicted the disease outcome in patients with DLBCL. This association was evident when relating intensity to patient survival (p=0.0321) and strengthened when a score was calculated based on both staining intensity and the proportion of the reactive tumour cells (p=0.0128; reduction in the mean survival times: 35% and 46%, respectively). Elevated expression of bcl-2 protein also identified the high-risk patients (p=0.0095; reduction in mean survival time: 37%). Over-expression of both factors was a more powerful indicator of poor prognosis than either marker alone (p=0.0054, 70% reduction in mean survival time). In conclusion, our novel F2-9C3 monoclonal antibody is effective in determination of expression of IAP-survivin in neoplastic tissue. Nuclear overexpression of IAP-survivin using this antibody predicts the disease outcome in patients with DLBCL and significantly improves the predictive power of bcl-2 in these patients.
 ...
PMID:A new subtype-specific monoclonal antibody for IAP-survivin identifies high-risk patients with diffuse large B-cell lymphoma and improves the prognostic value of bcl-2. 1809 43

On a global scale, gastric carcinoma is the second leading course of the cancer-related deaths. Recent studies have provided evidence that cagA-positive Helicobacter pylori plays a causal role for the development of gastric carcinoma. The cagA-encoded CagA protein is delivered into H. pylori-attached gastric epithelial cells via the bacterial type IV secretion system (TFSS). Delivered CagA undergoes tyrosine phosphorylation by Src family kinases at the conserved EPIYA motifs and then specifically binds and deregulates SHP-2 tyrosine phosphatase, a bona fide oncoprotein involved in human malignancies. As a result, CagA causes aberrant mitogenic signal as well as elevated cell motility in gastric epithelial cells. Also, CagA specifically interacts with and inhibits PAR1b/MARK2 polarity-regulating kinase to disrupt tight junctions and cause loss of epithelial apical-basolateral cell polarity. These CagA activities have been suspected to play an important role in gastric carcinogenesis. Indeed, recently generated cagA-transgenic mice expressing CagA systemically developed gastrointestinal carcinomas as well hematopoietic malignancies such as myeloid leukemia and B-cell lymphoma. The observations collectively indicate that H. pylori CagA is the first identified bacterial oncoprotein involved in gastric carcinogenesis.
 ...
PMID:[Oncogenic mechanism of Helicobacter pylori]. 1858 23

The purpose of this study was to determine whether a dry bean (Phaseolus vulgaris, L.) containing diet exerts an inhibitory effect on mammary carcinogenesis in a well-characterized rodent model for breast cancer. Twenty-one-d-old female Sprague Dawley rats were given an intraperitoneal injection of 1-methyl-1-nitrosourea and 7 d after carcinogen injection were randomized to 1 of 5 groups fed a modification of the AIN-93G diet formulation containing 0, 7.5, 15, 30, or 60% (wt:wt) small red dry bean incorporated as cooked, freeze-dried, and milled powder. All experimental diets had the same macronutrient content based on proximate analysis. Compared with the control group, dry bean consumption resulted in dose-dependent reductions in mammary cancer incidence (P = 0.046), cancer multiplicity (P = 0.001), and tumor burden (P = 0.01). Dry bean consumption was associated with dose-dependent reductions in plasma concentrations of glucose, insulin, insulin-like growth factor-1, C-reactive protein, and interleukin-6 in food-deprived rats. Analysis of mammary adenocarcinomas indicated that a dominant mechanism accounting for reduced tumor burden was the induction of apoptosis. B cell lymphoma 2 and X-linked inhibitor of apoptosis protein levels decreased and BCL-2-associated X protein increased with increasing dry bean consumption, findings consistent with the induction of apoptosis via the mitochondrial pathway. These data demonstrate that a legume without noteworthy content of isoflavones inhibits the development of mammary carcinogenesis and are consistent with a recent report from the Nurses Health Study that bean or lentil intake is associated with a lower risk for breast cancer.
 ...
PMID:Mechanisms associated with dose-dependent inhibition of rat mammary carcinogenesis by dry bean (Phaseolus vulgaris, L.). 1893 3

Cdc6 play crucial roles in DNA replication and carcinogenesis. The biological significance of the Cdc6 G1321A polymorphism (V441I, rs13706) is still not elucidated. Here we examined the influence of this polymorphism on the function of Cdc6 and the individual's susceptibility to non-Hodgkin lymphoma (NHL) and hepatocellular carcinoma (HCC). Unconditional logistic regression analysis revealed that the risk for NHL was significantly reduced in both AG heterozygotes [odds ratio (OR)=0.67, P=0.019] and AA homozygotes (OR=0.54, P=0.026), compared with GG homozygotes. Further stratification by subtypes of NHL showed that the AG as well as combined AA/AG genotypes were associated with decreased risk for B-cell-NHL (OR=0.62, P=0.011 and OR=0.61, P=0.006, respectively), especially for diffuse large B-cell lymphoma (DLBCL, OR=0.63, P=0.025 and OR=0.62, P=0.012, respectively). In addition, male individuals with the AA genotype displayed borderline significantly reduced risk for HCC (OR=0.48, P=0.054). Interestingly, the G1321A polymorphism did not affect caspase-mediated cleavage of Cdc6 during etoposide-induced apoptosis, but it was predicted to alter the secondary structure of Cdc6 mRNA. Our data provide the first evidence that the Cdc6 G1321A polymorphism is associated with decreased risk of cancer. Further studies are necessary to confirm the general validity of our findings.
 ...
PMID:Association analysis between the Cdc6 G1321A polymorphism and the risk for non-Hodgkin lymphoma and hepatocellular carcinoma. 1910 72


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>