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  • 1
    Keywords: CELLS ; EXPRESSION ; BLOOD ; CELL ; THERAPY ; POPULATION ; RISK ; GENE ; PROTEIN ; PROTEINS ; MOLECULES ; LIGAND ; RESPONSES ; DNA ; MECHANISM ; DENDRITIC CELLS ; mechanisms ; T-CELLS ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; SUSCEPTIBILITY ; MOLECULE ; LYMPHOMA ; GRAVES-DISEASE ; WOMEN ; case-control studies ; IMMUNE-RESPONSE ; B-CELL LYMPHOMA ; NON-HODGKINS-LYMPHOMA ; case-control study ; SAN-FRANCISCO ; VARIANT ; INCREASE ; SINGLE NUCLEOTIDE POLYMORPHISMS ; SNPs ; non-Hodgkin lymphoma ; dendritic cell ; single-nucleotide polymorphism ; USA ; population-based ; B-CELL ; FRANCISCO BAY AREA ; non Hodgkin lymphoma ; interactions ; NUCLEOTIDE ; SOLUBLE CD40 LIGAND
    Abstract: CD40 and its ligand, CD154, are major costimulatory molecules whose interactions are important in humoral and cellular immunity. We hypothesized that single nucleotide polymorphisms (SNPs) in TNFRSF5 and TNFSF5 encoding the CD40 and CD154 proteins, respectively, influence lymphoma risk, particularly a functional TNFRSF5 SNP (-1C〉T, rs1883832) associated with reduced B-cell CD40 expression. TNFRSF5 and TNFSF5 SNPs were examined in a population-based case-control study of non-Hodgkin lymphoma (376 cases/801 controls with DNA), and compelling findings were followed up in 2 independent populations. Pooled analyses of all 3 case-control studies (total N = 1776 non-Hodgkin lymphoma cases, N = 2482 controls) revealed an increased risk of follicular lymphoma (FL) associated with the TNFRSF5-1TT genotype (odds ratio = 1.6; 95% confidence interval, 1.1-2.4). In addition, among women, an inverse association was found between the variant A allele for a TNFSF5 6809G〉A SNP and FL risk (OR=.61; 95% Cl, 0.36-0.98). In genotype-phenotype studies, significantly reduced circulating soluble CD40 was observed in TNFRSF5-1TT compared with -1CC carriers. Further, dendritic cells from those with -1TT versus -1CC genotypes exhibited lower CD40 cell surface expression. These results suggest that the TNFRSF5 -1C〉T polymorphism may increase FL susceptibility through mechanisms that hinder cellular immune responses. Further studies are needed to explore these findings
    Type of Publication: Journal article published
    PubMed ID: 18287517
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  • 2
    Keywords: RISK ; COMPLEX ; COMPLEXES ; ASSOCIATION ; POLYMORPHISMS ; SUSCEPTIBILITY ; VARIANTS ; LYMPHOMA ; genetics ; HLA ; FOLLICULAR LYMPHOMA ; VARIANT ; HIGH-RESOLUTION ; non-Hodgkin lymphoma ; SUBTYPES ; HAPLOTYPE ; LOCUS ; LOCI ; susceptibility loci ; NON-HODGKIN-LYMPHOMA ; GENOME-WIDE ASSOCIATION ; GENETIC-VARIATION ; non-Hodgkin ; Genetic ; NECROSIS-FACTOR TNF
    Abstract: To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 x 10(-29) and rs7755224, combined P = 2.00 x 10(-19); r(2) = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 x 10(-9))
    Type of Publication: Journal article published
    PubMed ID: 20639881
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  • 3
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    Haematologica 92 (7), 960-969 
    Keywords: ENERGIES ; GROWTH ; SURVIVAL ; COMMON ; DISEASE ; POPULATION ; RISK ; GENE ; GENES ; METABOLISM ; MECHANISM ; GENETIC POLYMORPHISMS ; mechanisms ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; SUSCEPTIBILITY ; VARIANTS ; DELETION ; hormone ; LYMPHOMA ; ENERGY ; SNP ; NECROSIS-FACTOR-ALPHA ; POPULATIONS ; genetic polymorphism ; REPLICATION ; case-control studies ; ALCOHOL ; EPSTEIN-BARR-VIRUS ; FAMILY-CANCER DATABASE ; CHRONIC LYMPHOCYTIC-LEUKEMIA ; B-CELL LYMPHOMA ; DNA-REPAIR GENES ; CROSS-TALK ; case control study ; case-control study ; NHL ; review ; ASSOCIATIONS ; VARIANT ; ALLELE ; PENETRANCE ; regulation ; non-Hodgkin lymphoma ; ALLELES ; case control studies ; USA ; GENETIC SUSCEPTIBILITY ; INCREASED RISK ; B-CELL ; NON-HODGKIN-LYMPHOMA ; case control ; hematology ; case-control ; GENETIC-SUSCEPTIBILITY ; FOLATE-METABOLIZING GENES ; OXIDATIVE STRESS GENES ; S-TRANSFERASE GENOTYPES
    Abstract: Genetic susceptibility studies of lymphoma may serve to identify at risk populations and clarify important disease mechanisms. This review considered all studies published through October 2006 on the contribution of genetic polymorphisms in the risk of lymphoma. Numerous studies implicate the role of genetic variants that promote B-cell survival and growth with increased risk of lymphoma. Several reports including a large pooled study by InterLymph, an international consortium of non-Hodgkin lymphoma (NHL) case-control studies, found positive associations between variant alleles in TNF -308G 〉 A and IL10 -3575T 〉 A genes and risk of diffuse large B-cell lymphoma. Four studies reported positive associations between a GSTT1 deletion and risk of Hodgkin and non-Hodgkin lymphoma. Genetic studies of folate-metabolizing genes implicate folate in NHL risk, but further studies that include folate and alcohol intakes are needed. Links between NHL and genes involved in energy regulation and hormone production and metabolism may provide insights into novel mechanisms implicating neuro- and endocrine-immune cross-talk with lymphomagenesis. However, this links will need replication in larger populations. Numerous studies suggest that common genetic variants with low penetrance influence lymphoma risk, though replication studies will be needed to eliminate false positive associations
    Type of Publication: Journal article published
    PubMed ID: 17606447
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  • 4
    Keywords: validation ; ASSOCIATION ; POLYMORPHISMS ; SUSCEPTIBILITY ; VARIANTS ; LYMPHOMA ; genetics ; REGION ; FOLLICULAR LYMPHOMA ; PSORIASIS ; VARIANT ; non-Hodgkin lymphoma ; USA ; NON-HODGKIN-LYMPHOMA ; GENOME-WIDE ASSOCIATION ; Genetic ; Genome-wide association studies ; Illumina
    Abstract: We conducted genome-wide association studies of non-Hodgkin lymphoma using Illumina HumanHap550 BeadChips to identify subtype-specific associations in follicular, diffuse large B-cell and chronic lymphocytic leukemia/small lymphocytic lymphomas. We found that rs6457327 on 6p21.33 was associated with susceptibility to follicular lymphoma (FL; N = 189 cases, 592 controls) with validation in another 456 FL cases and 2,785 controls (combined allelic P = 4.7 x 10(-11)). The region of strongest association overlapped C6orf15 (STG), located near psoriasis susceptibility region 1 (PSORS1)
    Type of Publication: Journal article published
    PubMed ID: 19620980
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  • 5
    Keywords: RISK ; GENE ; GENES ; ASSOCIATION ; polymorphism ; SUSCEPTIBILITY ; LYMPHOMA ; PROMOTER ; meta-analysis ; FOLLICULAR LYMPHOMA ; SYSTEMIC-LUPUS-ERYTHEMATOSUS ; VARIANT ; RHEUMATOID-ARTHRITIS ; ALLELES ; pooled analysis ; B-CELL ; SUBGROUPS ; INTERLEUKIN-10 ; SUN EXPOSURE ; GENETIC-VARIATION ; non-Hodgkin ; Genetic ; IMMUNE ; single nucleotide ; lymphotoxin-alpha ; tumor necrosis factor-alpha
    Abstract: In an International Lymphoma Epidemiology Consortium pooled analysis, polymorphisms in 2 immune-system-related genes, tumor necrosis factor (TNF) and interleukin-10 (IL10), were associated with non-Hodgkin lymphoma (NHL) risk. Here, 8,847 participants were added to previous data (patients diagnosed from 1989 to 2005 in 14 case-control studies; 7,999 cases, 8,452 controls) for testing of polymorphisms in the TNF -308G 〉 A (rs1800629), lymphotoxin-alpha (LTA) 252A 〉 G (rs909253), IL10 -3575T 〉 A (rs1800890, rs1800896), and nucleotide-binding oligomerization domain containing 2 (NOD2) 3020insC (rs2066847) genes. Odds ratios were estimated for non-Hispanic whites and several ethnic subgroups using 2-sided tests. Consistent with previous findings, odds ratios were increased for "new" participant TNF -308A carriers (NHL: per-allele odds ratio (ORallelic) = 1.10, P-trend = 0.001; diffuse large B-cell lymphoma (DLBCL): ORallelic = 1.23, P-trend = 0.004). In the combined population, odds ratios were increased for TNF -308A carriers (NHL: ORallelic = 1.13, P-trend = 0.0001; DLBCL: ORallelic = 1.25, P-trend = 3.7 x 10(-6); marginal zone lymphoma: ORallelic = 1.35, P-trend = 0.004) and LTA 252G carriers (DLBCL: ORallelic = 1.12, P-trend = 0.006; mycosis fungoides: ORallelic = 1.44, P-trend = 0.015). The LTA 252A 〉 G/TNF -308G 〉 A haplotype containing the LTA/TNF variant alleles was strongly associated with DLBCL (P = 2.9 x 10(-8)). Results suggested associations between IL10 -3575T 〉 A and DLBCL (P-trend = 0.02) and IL10 -1082A 〉 G and mantle cell lymphoma (P-trend = 0.04). These findings strengthen previous results for DLBCL and the LTA 252A 〉 G/TNF -308A locus and provide robust evidence that these TNF/LTA gene variants, or others in linkage disequilibrium, are involved in NHL etiology
    Type of Publication: Journal article published
    PubMed ID: 20047977
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