scholarly journals Single Nucleotide Polymorphisms in MIR143 Contribute to Protection Against Non-Hodgkin Lymphoma (NHL) in Caucasian Populations

Genes ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 185 ◽  
Author(s):  
Gabrielle Bradshaw ◽  
Larisa M. Haupt ◽  
Eunise M. Aquino ◽  
Rodney A. Lea ◽  
Heidi G. Sutherland ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Multiple Testing ◽  
Genome Wide Association Study ◽  
Treatment Options ◽  
Significant Snps ◽  
Mass Spectrometry Analysis ◽  
Nucleotide Polymorphisms ◽  
Spectrometry Analysis ◽  
Non Hodgkin Lymphoma ◽  
Reduced Risk

Recent studies show an association of microRNA (miRNA) polymorphisms (miRSNPs) in different cancer types, including non-Hodgkin lymphoma (NHL). The identification of miRSNPs that are associated with NHL susceptibility may provide biomarkers for early diagnosis and prognosis for patients who may not respond well to current treatment options, including the immunochemotherapy drug combination that includes rituximab, cyclophosphamide, doxorubicin, vincristine and prednisome (R-CHOP). We developed a panel of miRSNPs for genotyping while using multiplex PCR and chip-based mass spectrometry analysis in an Australian NHL case-control population (300 cases, 140 controls). Statistical association with NHL susceptibility was performed while using Chi-square (χ2) and logistic regression analysis. We identified three SNPs in MIR143 that are to be significantly associated with reduced risk of NHL: rs3733846 (odds ratio (OR) [95% confidence interval (CI)] = 0.54 [0.33 – 0.86], p = 0.010), rs41291957 (OR [95% CI] = 0.61 [0.39 – 0.94], p = 0.024), and rs17723799 (OR [95% CI] = 0.43 [0.26 – 0.71], p = 0.0009). One SNP, rs17723799, remained significant after correction for multiple testing (p = 0.015). Subsequently, we investigated an association between the rs17723799 genotype and phenotype by measuring target gene Hexokinase 2 (HKII) expression in cancer cell lines and controls. Our study is the first to report a correlation between miRSNPs in MIR143 and a reduced risk of NHL in Caucasians, and it is supported by significant SNPs in high linkage disequilibrium (LD) in a large European NHL genome wide association study (GWAS) meta-analysis.

scholarly journals Identification of Predictive Pathways for Non-Hodgkin Lymphoma Prognosis

2010 ◽  
Vol 9 ◽  
pp. CIN.S6315 ◽  
Author(s):  
Xuesong Han ◽  
Yang Li ◽  
Jian Huang ◽  
Yawei Zhang ◽  
Theodore Holford ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Predictive Power ◽  
B Cell Lymphoma ◽  
Separate Analysis ◽  
Nucleotide Polymorphisms ◽  
Clinical Factors ◽  
Single Nucleotide ◽  
Kegg Pathways ◽  
Non Hodgkin Lymphoma ◽  
Individual Snps

Despite decades of intensive research, NHL (non-Hodgkin lymphoma) still remains poorly understood and is largely incurable. Recent molecular studies suggest that genomic variants measured with SNPs (single nucleotide polymorphisms) in genes may have additional predictive power for NHL prognosis beyond clinical risk factors. We analyzed a genetic association study. The prognostic cohort consisted of 346 patients, among whom 138 had DLBCL (diffuse large B-cell lymphoma) and 101 had FL (follicular lymphoma). For DLBCL, we analyzed 1229 SNPs which represented 122 KEGG pathways. For FL, we analyzed 1228 SNPs which represented 122 KEGG pathways. Unlike in existing studies, we targeted at identifying pathways with significant additional predictive power beyond clinical factors. In addition, we accounted for the joint effects of multiple SNPs within pathways, whereas some existing studies drew pathway-level conclusions based on separate analysis of individual SNPs. For DLBCL, we identified four pathways, which, combined with the clinical factors, had medians of the prediction logrank statistics as 2.535, 2.220, 2.094, 2.453, and 2.512, respectively. As a comparison, the clinical factors had a median of the prediction logrank statistics around 0.552. For FL, we identified two pathways, which, combined with the clinical factors, had medians of the prediction logrank statistics as 4.320 and 3.532, respectively. As a comparison, the clinical factors had a median of the prediction logrank statistics around 1.212. For NHL overall, we identified three pathways, which, combined with the clinical factors, had medians of the prediction logrank statistics as 5.722, 5.314, and 5.441, respective. As a comparison, the clinical factors had a median of the prediction logrank statistics around 4.411. The identified pathways have sound biological bases. In addition, they are different from those identified using existing approaches. They may provide further insights into the biological mechanisms underlying the prognosis of NHL.

scholarly journals Oncogenic KRAS engages an RSK1/NF1 pathway to inhibit wild-type RAS signaling in pancreatic cancer

2021 ◽  
Vol 118 (21) ◽  
pp. e2016904118
Author(s):  
Derek K. Cheng ◽  
Tobiloba E. Oni ◽  
Jennifer S. Thalappillil ◽  
Youngkyu Park ◽  
Hsiu-Chi Ting ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Success ◽  
Treatment Options ◽  
Mass Spectrometry Analysis ◽  
Ductal Adenocarcinoma ◽  
Ras Signaling ◽  
Wild Type ◽  
Feedback Mechanisms ◽  
Spectrometry Analysis ◽  
Pancreatic Cancer Cells

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with limited treatment options. Although activating mutations of the KRAS GTPase are the predominant dependency present in >90% of PDAC patients, targeting KRAS mutants directly has been challenging in PDAC. Similarly, strategies targeting known KRAS downstream effectors have had limited clinical success due to feedback mechanisms, alternate pathways, and dose-limiting toxicities in normal tissues. Therefore, identifying additional functionally relevant KRAS interactions in PDAC may allow for a better understanding of feedback mechanisms and unveil potential therapeutic targets. Here, we used proximity labeling to identify protein interactors of active KRAS in PDAC cells. We expressed fusions of wild-type (WT) (BirA-KRAS4B), mutant (BirA-KRAS4BG12D), and nontransforming cytosolic double mutant (BirA-KRAS4BG12D/C185S) KRAS with the BirA biotin ligase in murine PDAC cells. Mass spectrometry analysis revealed that RSK1 selectively interacts with membrane-bound KRASG12D, and we demonstrate that this interaction requires NF1 and SPRED2. We find that membrane RSK1 mediates negative feedback on WT RAS signaling and impedes the proliferation of pancreatic cancer cells upon the ablation of mutant KRAS. Our findings link NF1 to the membrane-localized functions of RSK1 and highlight a role for WT RAS signaling in promoting adaptive resistance to mutant KRAS-specific inhibitors in PDAC.

scholarly journals Genome-Wide Association study Identifies a Novel Association Between a Cardiovascular Gene Polymorphism and Superior Athletic Performance

2020 ◽  
Author(s):  
Mohamed Elrayess ◽  
Fatima Al-Khelaifi ◽  
Noha Yousri ◽  
Omar Al-Bagha
Keyword(s):  
Athletic Performance ◽  
Genome Wide Association Study ◽  
Endurance Athlete ◽  
Meta Analysis ◽  
Significant Snps ◽  
Nucleotide Polymorphisms ◽  
Replication Studies ◽  
Genome Wide ◽  
Small Effect Size ◽  
Metabolomics Analysis

Research into the genetic predisposition to superior athletic performance has been a hindered by the underpowered studies and the small effect size of identified genetic variants. The aims of this study were to investigate the association of common single-nucleotide polymorphisms (SNPs) with endurance athlete status in a large cohort of elite European athletes using GWAS approach, followed by replication studies in Russian and Japanese elite athletes and functional validation using metabolomics analysis. Results: The association of 476,728 SNPs of Illumina DrugCore Gene chip and endurance athlete status was investigated in 796 European international-level athletes (645 males, 151 females) by comparing allelic frequencies between athletes specialized in sports with high (n=662) and low/moderate (n=134) aerobic component. Validation of results was performed by comparing the frequencies of the most significant SNPs between 242 and 168 elite Russian high and low/moderate aerobic athletes, respectively, and between 60 elite Japanese endurance athletes and 406 controls. A meta-analysis has identified rs1052373 (GG homozygotes) in Myosin Binding Protein (MYBPC3; implicated in cardiac hypertrophic myopathy) gene to be associated with endurance athlete status (P=1.43E-08, odd ratio 2.2). Homozygotes carriers of rs1052373 G allele in Russian athletes had significantly greater VO2max than carriers of the AA+AG (P = 0.005). Subsequent metabolomics analysis revealed several amino acids and lipids associated with rs1052373 G allele (1.82x10-05) including the testosterone precursor androstenediol (3beta, 17beta) disulfate. Conclusion: This is the first report of genome-wide significant SNP and related metabolites associated with elite athlete status. Further investigations of the functional relevance of the identified SNPs and metabolites in relation to enhanced athletic performance are warranted.

scholarly journals Mantle Cell Lymphoma Mimicking Rectal Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-4
Author(s):  
Engin Kelkitli ◽  
Hilmi Atay ◽  
Levent Yıldız ◽  
Ahmet Bektaş ◽  
Mehmet Turgut
Keyword(s):  
Mantle Cell Lymphoma ◽  
Hodgkin Lymphoma ◽  
Rectal Carcinoma ◽  
Cell Lymphoma ◽  
Treatment Options ◽  
Extranodal Involvement ◽  
Non Hodgkin Lymphoma ◽  
Rectal Involvement ◽  
Mantle Cell ◽  
Rectal Mass

Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin lymphoma. After the (11;14) translocation was identified as its constant finding in 1992, MCL was recognized as a separate subgroup of non-Hodgkin lymphoma (NHL). In MCL, extranodal involvement may be observed in the bone marrow, the spleen, the liver, and the gastrointestinal system (GIS). Cases of MCL that present with a massive and solitary rectal mass are rare in the literature. In this case report, our aim was to present an MCL patient with a rarely observed solitary rectal involvement mimicking rectal carcinoma and to discuss treatment options for this patient.

scholarly journals trans Fatty Acid Intake Is Associated with Increased Risk and n3 Fatty Acid Intake with Reduced Risk of Non-Hodgkin Lymphoma

2013 ◽  
Vol 143 (5) ◽  
pp. 672-681 ◽  
Author(s):  
Bridget Charbonneau ◽  
Helen M. O'Connor ◽  
Alice H. Wang ◽  
Mark Liebow ◽  
Carrie A. Thompson ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Hodgkin Lymphoma ◽  
Trans Fatty Acid ◽  
Fatty Acid Intake ◽  
Acid Intake ◽  
Non Hodgkin Lymphoma ◽  
Trans Fatty Acid Intake ◽  
Increased Risk ◽  
Reduced Risk

HLA-A*02 is associated with a reduced risk and HLA-A*01 with an increased risk of developing EBV+ Hodgkin lymphoma

Blood ◽  
2007 ◽  
Vol 110 (9) ◽  
pp. 3310-3315 ◽  
Author(s):  
Marijke Niens ◽  
Ruth F. Jarrett ◽  
Bouke Hepkema ◽  
Ilja M. Nolte ◽  
Arjan Diepstra ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Hla Class I ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Barr Virus ◽  
Increased Risk ◽  
Peptide Binding Groove ◽  
Epstein Barr ◽  
Binding Groove ◽  
Reduced Risk

AbstractPrevious studies showed that the HLA class I region is associated with Epstein-Barr virus (EBV)–positive Hodgkin lymphoma (HL) and that HLA-A is the most likely candidate gene in this region. This suggests that antigenic presentation of EBV-derived peptides in the context of HLA-A is involved in the pathogenesis of EBV+ HL by precluding efficient immune responses. We genotyped exons 2 and 3, encoding the peptide-binding groove of HLA-A, for 32 single nucleotide polymorphisms in 70 patients with EBV+ HL, 31 patients with EBV− HL, and 59 control participants. HLA-A*01 was significantly overrepresented and HLA-A*02 was significantly underrepresented in patients with EBV+ HL versus controls and patients with EBV− HL. In addition, HLA-A*02 status was determined by immunohistochemistry or HLA-A*02–specific polymerase chain reaction (PCR) on 152 patients with EBV+ HL and 322 patients with EBV− HL. The percentage of HLA-A*02+ patients in the EBV+ HL group (35.5%) was significantly lower than in 6107 general control participants (53.0%) and the EBV− HL group (50.9%). Our results indicate that individuals carrying the HLA-A*02 allele have a reduced risk of developing EBV+ HL, while individuals carrying the HLA-A*01 allele have an increased risk. It is known that HLA-A*02 can present EBV-derived peptides and can evoke an effective immune response, which may explain the protective phenotype.

scholarly journals Single-Nucleotide Polymorphism Variations Associated With Specific Genes Putatively Identified Enhanced Genetic Predisposition for 305-Day Milk Yield in the Girolando Crossbreed

2021 ◽  
Vol 11 ◽  
Author(s):  
Alex Silva da Cruz ◽  
Danilo Conrado Silva ◽  
Lysa Bernardes Minasi ◽  
Larissa Kamídia de Farias Teixeira ◽  
Flávia Melo Rodrigues ◽  
...  
Keyword(s):  
Milk Production ◽  
Milk Yield ◽  
Genetic Predisposition ◽  
Fixed Effects ◽  
Genome Wide Association Study ◽  
Significant Snps ◽  
Nucleotide Polymorphisms ◽  
Production Traits ◽  
Single Nucleotide ◽  
A Genome

Milk production phenotypes are the main focus of genetic selection in dairy herds, and although there are many genes identified as related to the biology of these traits in pure breeds, little is known about crossbreed animals. This study aimed to identify potential genes associated with the 305-day milk yield in 337 crossbreed Gir × Holstein (Girolando) animals. Milk production records were genotyped for 45,613 single-nucleotide polymorphisms (SNPs). This dataset was used for a genome-wide association study (GWAS) using the 305-day milk yield adjusted for the fixed effects of herd and year and linear and quadratic effects of age at calving (in days) and calving factor averaged per animal. Genes within the significant SNPs were retrieved from the Bos taurus ARS-UCD1.2 assembly (bosTau9) for gene ontology analysis. In summary, the GWAS identified 52 SNPs associated [p ≤ 10–4, false discovery rate (FDR) = 8.77%] with milk production, including NUB1 and SLC24A2, which were previously described as related to milk production traits in cattle. The results suggest that SNPs associated mainly with NUB1 and SLC24A2 could be useful to understand milk production in Girolando and used as predictive markers for selecting genetic predisposition for milk yield in Girolando.

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