Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10-8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10-9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10-8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.

• MeSH
• celogenomová asociační studie MeSH
• genetická predispozice k nemoci * MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• nehodgkinský lymfom * genetika   MeSH
• rizikové faktory MeSH
• studie případů a kontrol MeSH
• zárodečné buňky MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH

Paeonia species have been valued for their ethnomedicinal uses in various countries and received much interest among the scientific community for their therapeutic properties, including anti-microbial, anti-inflammatory, anti-cancer, nephroprotective and hepatoprotective effects. The multiple phytotherapeutical applications of Paeonia species inspired us to establish the phytochemical fingerprint and to evaluate the biological properties of ethyl acetate, methanol, and aqueous extracts from the roots and aerial parts of two Paeonia species (P. arietina G. Anderson and P. kesrounansis Thiébaut). Phytoconstituents of P. arietina and P. kesrounansis extracts were analyzed using 1D and 2D NMR and LC-DAD-ESI-MS. The total content of phenolics (TPC) and flavonoids (TFC) in the extracts was also evaluated. The antioxidant activity was profiled using DPPH, ABTS, CUPRAC, FRAP, phosphomolybdenum, and metal chelation assays. Enzyme inhibitory properties were evaluated against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, α-amylase, and α-glucosidase. Phytochemical analysis of P. arietina and P. kesrounansis extracts showed the presence of galloyl esters of sugars, galloyl monoterpenes, and glycosylated flavonoids. The three solvent extracts presented different behavior in the bioassays. The highest antioxidant activity, tyrosinase and AChE inhibition were observed for the methanolic extract of the aerial parts of P. kesrounansis. In addition, the ethyl acetate extracts of the aerial parts of both plants were the most effective inhibitors of α-amylase. The highest BChE inhibition was observed for root methanolic extract of P. kesrounansis while the root ethyl acetate extract of P. arietina exerted the strongest inhibition of α-glucosidase. Methanol extract of P. kesrounansis aerial parts presented the highest TPC, while TFC was greatest in the corresponding extract of P. arietina. Our findings can be considered as a starting point for future studies to further validate the effectiveness and safety profiles of these plants in folk medicine.

• MeSH
• antioxidancia chemie   izolace a purifikace   farmakologie   MeSH
• chromatografie kapalinová metody   MeSH
• fenoly analýza   izolace a purifikace   MeSH
• flavonoidy analýza   izolace a purifikace   MeSH
• hmotnostní spektrometrie s elektrosprejovou ionizací metody   MeSH
• inhibitory enzymů chemie   izolace a purifikace   farmakologie   MeSH
• kořeny rostlin MeSH
• nadzemní části rostlin MeSH
• Paeonia chemie   MeSH
• rostlinné extrakty chemie   farmakologie   MeSH
• rozpouštědla chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. Results: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions: These data suggest several plausible genetic links between DLBCL and SLE.

• Publikační typ
• časopisecké články MeSH

Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82,P-value = 8.5 × 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51,P-value = 4.0 × 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.

• MeSH
• B-buněčný lymfom genetika   patologie   MeSH
• dospělí MeSH
• genetická predispozice k nemoci * MeSH
• genetické asociační studie metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• prospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• telomery patologie   MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH

Marginal zone lymphoma (MZL) is the third most common subtype of B-cell non-Hodgkin lymphoma. Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127 controls of European ancestry and identify two independent loci near BTNL2 (rs9461741, P=3.95 × 10(-15)) and HLA-B (rs2922994, P=2.43 × 10(-9)) in the HLA region significantly associated with MZL risk. This is the first evidence that genetic variation in the major histocompatibility complex influences MZL susceptibility.

• MeSH
• běloši genetika   MeSH
• celogenomová asociační studie MeSH
• genotyp MeSH
• hlavní histokompatibilní komplex genetika   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé MeSH
• lymfom z B-buněk marginální zóny genetika   MeSH
• membránové glykoproteiny genetika   MeSH
• výpočetní biologie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH

Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 × 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 × 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 × 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 × 10(-13) and 3.63 × 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.

• MeSH
• běloši genetika   MeSH
• celogenomová asociační studie MeSH
• difúzní velkobuněčný B-lymfom genetika   MeSH
• genetická predispozice k nemoci genetika   MeSH
• genetické lokusy genetika   MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé MeSH
• lokus kvantitativního znaku genetika   MeSH
• mapování chromozomů MeSH
• pravděpodobnostní funkce MeSH
• výpočetní biologie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• Research Support, N.I.H., Intramural MeSH

Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [OR(per-allele)] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (OR(per-allele) = 1.23; p = 8.23 × 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.

• MeSH
• alely MeSH
• celogenomová asociační studie * MeSH
• folikulární lymfom genetika   MeSH
• genetická predispozice k nemoci * MeSH
• haplotypy genetika   MeSH
• HLA antigeny genetika   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé MeSH
• lidské chromozomy genetika   MeSH
• nádorové biomarkery genetika   MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Intramural MeSH
• srovnávací studie MeSH