Single nucleotide polymorphisms analysis of BRAC and ERCC1 as predictor of recurrence after chemoradiation for cervical cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13540-e13540
Author(s):  
Luis Roberto Féliz ◽  
Verónica Pereira ◽  
Mariano Monzo ◽  
Carmen Munoz ◽  
Pere Fuste ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Single Nucleotide Polymorphisms ◽  
Locally Advanced ◽  
Initial Response ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Single Nucleotide ◽  
Number Of Patients ◽  
The Status ◽  
Grade 3

e13540 Background: A number of patients with locally advanced cervical cancer will recur despite presenting initial response to chemoradiation. Single-nucleotide polymorphisms (SNP) of DNA repair genes have been found to be predictors of efficacy of chemotherapy and radiotherapy. Methods: We evaluated the presence of SNP in ERCC1, BRAC 1 and 2 genes. We analysed paraffin-embedded biopsies from patients who had relapsed after receiving treatment with chemoradiation, for SNP of the mentioned genes. The status of the alleles wild type (wt) or at least 1 SNP was compared with time to progression (TTP) and toxicity. Results: 90 patients who experience recurrence of their cervical cancer were included in the analysis. Of those, we only could obtain evaluable tumour from 43 patients. Median age: 52.5 yrs (31-81). Histology: 32 squamous cell, 8 adenocarcinoma, 3 adenosquamous. One SNP in BRAC1 (rs12516) was found to be significantly associated with better TTP for the mutant variant compared to the wild-type (124 m. vs. 14 m.). Furthermore, all six patients who presented with severe (grade 3-4) toxicity had this wild-type SNP (rs12516) in BRAC1 gene. Conclusions: We have identified a SNP which confers better outcome in patients with cervical cancer. Further analysis need to be done to determine its relation to radiation-induced toxicity in this group of patients.

Analysis of 4 Single-Nucleotide Polymorphisms in Relation to Cervical Dysplasia and Cancer Development Using a High-Throughput Ligation-Detection Reaction Procedure

2011 ◽  
Vol 21 (9) ◽  
pp. 1664-1671 ◽  
Author(s):  
Helmut von Keyserling ◽  
Thomas Bergmann ◽  
Miriam Schuetz ◽  
Ursula Schiller ◽  
Jonas Stanke ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Single Nucleotide Polymorphisms ◽  
Genetic Markers ◽  
Cervical Dysplasia ◽  
Semantic Integration ◽  
Cancer Development ◽  
Large Sample Size ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genetic Characteristics

BackgroundHost genetic characteristics and environmental factors may correlate with risk for cervical cancer development. Here we describe a retrospective screening study for single nucleotide polymorphisms (SNPs) in genetic markersTP53, MTHFR, CYP1A1,andCYP2E1in 749 patients.MethodsA multiplex ligation-dependent polymerase chain reaction approach was applied. We used archived material from human papillomavirus tests and correlated SNP genotypes to the corresponding clinical data. Semantic integration was used to identify and evaluate the clinical status from electronic health records.ResultsAn association with cervical cancer and high-grade dysplasia was found for the rare homozygous CC genotype (rs4646903) inCYP1A1(odds ratio [OR], 8.862). Odds ratios were also significantly elevated for heterozygousMTHFRCT genotype (rs1801133; OR, 1.457). No significant association was found inTP53(rs1042522) andCYP2E1(rs3813867). In addition, we found smokers at higher risk (OR, 2.688) and identified pregnancies as a significant risk factor (OR, 1.54).ConclusionsOur protocol enables a feasible way for further retrospective large sample size evaluation of potential genetic markers. This study revealed genetic associations of a rare SNP genotype with cervical dysplasia in one of the largest patient sample to date that warrants further investigation.

Associations between varied susceptibilities of PfATP4 inhibitors and genotypes in Ugandan Plasmodium falciparum isolates

2021 ◽  
Author(s):  
Oriana Kreutzfeld ◽  
Stephanie A. Rasmussen ◽  
Aarti A. Ramanathan ◽  
Patrick K. Tumwebaze ◽  
Oswald Byaruhanga ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Single Nucleotide Polymorphisms ◽  
Ex Vivo ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Single Nucleotide ◽  
Field Isolates ◽  
Frequent Mutations ◽  
Mixed Field ◽  
P Type

Among novel compounds under recent investigation as potential new antimalarial drugs are three independently developed inhibitors of the Plasmodium falciparum P-type ATPase (PfATP4): KAE609 (cipargamin), PA92, and SJ733. We assessed ex vivo susceptibilities to these compounds of 374 fresh P. falciparum isolates collected in Tororo and Busia districts, Uganda from 2016-2019. Median IC 50 s were 65 nM for SJ733, 9.1 nM for PA92, and 0.5 nM for KAE609. Sequencing of pfatp4 for 218 of these isolates demonstrated many non-synonymous single nucleotide polymorphisms; the most frequent mutations were G1128R (69% of isolates mixed or mutant), Q1081K/R (68%), G223S (25%), N1045K (16%) and D1116G/N/Y (16%). The G223S mutation was associated with decreased susceptibility to SJ733, PA92 and KAE609. The D1116G/N/Y mutations were associated with decreased susceptibility to SJ733, and the presence of mutations at both codons 223 and 1116 was associated with decreased susceptibility to PA92 and SJ733. In all of these cases, absolute differences in susceptibilities of wild type (WT) and mutant parasites were modest. Analysis of clones separated from mixed field isolates consistently identified mutant clones as less susceptible than WT. Analysis of isolates from other sites demonstrated presence of the G223S and D1116G/N/Y mutations across Uganda. Our results indicate that malaria parasites circulating in Uganda have a number of polymorphisms in PfATP4 and that modestly decreased susceptibility to PfATP4 inhibitors is associated with some mutations now present in Ugandan parasites.

scholarly journals Association of single-nucleotide polymorphisms in the ESR2 and FSHR genes with poor ovarian response in infertile Jordanian women

2021 ◽  
Vol 48 (1) ◽  
pp. 69-79
Author(s):  
Amer Mahmoud Sindiani ◽  
Osamah Batiha ◽  
Esra’a Al-zoubi ◽  
Sara Khadrawi ◽  
Ghadeer Alsoukhni ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Statistical Significance ◽  
Ovarian Response ◽  
Control Group ◽  
P Value ◽  
Case Group ◽  
Nucleotide Polymorphisms ◽  
Poor Ovarian Response ◽  
Single Nucleotide ◽  
Number Of Patients

Objective: Poor ovarian response (POR) refers to a subnormal follicular response that leads to a decrease in the quality and quantity of the eggs retrieved after ovarian stimulation during assisted reproductive treatment (ART). The present study investigated the associations of multiple variants of the estrogen receptor 2 (ESR2) and follicle-stimulating hormone receptor (FSHR) genes with POR in infertile Jordanian women undergoing ART.Methods: Four polymorphisms, namely ESR2 rs1256049, ESR2 rs4986938, FSHR rs6165, and FSHR rs6166, were investigated in 60 infertile Jordanian women undergoing ART (the case group) and 60 age-matched fertile women (the control group), with a mean age of 33.60±6.34 years. Single-nucleotide polymorphisms (SNPs) were detected by restriction fragment length polymorphism and then validated using Sanger sequencing.Results: The p-value of the difference between the case and control groups regarding FSHR rs6166 was very close to 0.05 (p=0.054). However, no significant differences were observed between the two groups in terms of the other three SNPs, namely ESR2 rs1256049, ESR2 rs4986938, and FSHR rs6165 (p=0.561, p=0.433, and p=0.696, respectively).Conclusion: The association between FSHR rs6166 and POR was not statistically meaningful in the present study, but the near-significant result of this experiment suggests that statistical significance might be found in a future study with a larger number of patients.

scholarly journals Causal Role of Single Nucleotide Polymorphisms within themprFGene of Staphylococcus aureus in Daptomycin Resistance

2013 ◽  
Vol 57 (11) ◽  
pp. 5658-5664 ◽  
Author(s):  
Soo-Jin Yang ◽  
Nagendra N. Mishra ◽  
Aileen Rubio ◽  
Arnold S. Bayer
Keyword(s):  
Staphylococcus Aureus ◽  
Single Nucleotide Polymorphisms ◽  
Point Mutations ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Single Nucleotide ◽  
Content Type ◽  
Reading Frame ◽  
A Charge

ABSTRACTSingle nucleotide polymorphisms (SNPs) within themprFopen reading frame (ORF) have been commonly observed in daptomycin-resistant (DAPr)Staphylococcus aureusstrains. Such SNPs are usually associated with a gain-in-function phenotype, in terms of either increased synthesis or enhanced translocation (flipping) of lysyl-phosphatidylglycerol (L-PG). However, it is unclear if suchmprFSNPs are causal in DAPrstrains or are merely a biomarker for this phenotype. In this study, we used an isogenic set ofS. aureusstrains: (i) Newman, (ii) its isogenic ΔmprFmutant, and (iii) several intransplasmid complementation constructs, expressing either a wild-type or point-mutated form of themprFORF cloned from two isogenic DAP-susceptible (DAPs)-DAPrstrain pairs (616-701 and MRSA11/11-REF2145). Complementation of the ΔmprFstrain with singly point-mutatedmprFgenes (mprFS295LormprFT345A) revealed that (i) individual and distinct point mutations within themprFORF can recapitulate phenotypes observed in donor strains (i.e., changes in DAP MICs, positive surface charge, and cell membrane phospholipid profiles) and (ii) these gain-in-function SNPs (i.e., enhanced L-PG synthesis) likely promote reduced DAP binding toS. aureusby a charge repulsion mechanism. Thus, for these two DAPrstrains, the definedmprFSNPs appear to be causally related to this phenotype.

scholarly journals XRCC2 R188H (rs3218536), XRCC3 T241M (rs861539) and R243H (rs77381814) Single Nucleotide Polymorphisms in Cervical Cancer Risk

2013 ◽  
Vol 19 (3) ◽  
pp. 553-558 ◽  
Author(s):  
Luis Orlando Pérez ◽  
Andrea Crivaro ◽  
Gisela Barbisan ◽  
Lucia Poleri ◽  
Carlos Daniel Golijow
Keyword(s):  
Cervical Cancer ◽  
Cancer Risk ◽  
Single Nucleotide Polymorphisms ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Cervical Cancer Risk

scholarly journals Influence of Genetic Variation in COMT on Cisplatin-Induced Nephrotoxicity in Cancer Patients

Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 358
Author(s):  
Bram C. Agema ◽  
Stijn L.W. Koolen ◽  
Mirjam de With ◽  
Nadia van Doorn ◽  
Niels Heersche ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Odds Ratio ◽  
Chemotherapeutic Agent ◽  
Kidney Injury ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Number Of Patients ◽  
Low Incidence ◽  
Grade 3

Cisplatin is a chemotherapeutic agent widely used for multiple indications. Unfortunately, in a substantial set of patients treated with cisplatin, dose-limiting acute kidney injury (AKI) occurs. Here, we assessed the association of 3 catechol-O-methyltransferase (COMT) single nucleotide polymorphisms (SNPs) with increased cisplatin-induced nephrotoxicity. In total, 551 patients were genotyped for the 1947 G>A (Val158Met, rs4680), c.615 + 310 C>T (rs4646316), and c.616–367 C>T (rs9332377) polymorphisms. Associations between these variants and AKI grade ≥3 were studied. The presence of a homozygous variant of c.616-367C>T was associated with a decreased occurrence of AKI grade 3 toxicity (p = 0.014, odds ratio (OR) 0.201, 95% confidence interval (CI) (0.047–0.861)). However, we could not exclude the role of dehydration as a potential cause of AKI in 25 of the 27 patients with AKI grade 3, which potentially affected the results substantially. As a result of the low incidence of AKI grade 3 in this dataset, the lack of patients with a COMT variant, and the high number of patients with dehydration, the association between COMT variants and AKI does not seem clinically relevant.

Single nucleotide polymorphisms (SNPs) analysis of CYP2C8, GSTT1, GSTP1, MDR1(A), MDR1(B) and ERCC1 as predictor of survival after weekly paclitaxel for relapsed advanced head & neck cancer patients (AHNCP)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2540-2540 ◽  
Author(s):  
J. J. Grau ◽  
M. Monzo ◽  
M. Vargas ◽  
S. Jansa ◽  
m. Campayo ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Phase 1 ◽  
High Rate ◽  
Weekly Paclitaxel ◽  
Head Neck Cancer ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Single Nucleotide ◽  
The Status ◽  
Head Neck

2540 Background: Gene SNPs correlate with survival in cancer patients (pts) treated with chemotherapy (CHM). CYP2C8 and GSTT1, GTSP1 genes are involved in phase 1 and 2 drug cellular metabolisms respectively; MDR1(A) and MDR1(B) are involved in drug membrane transport and ERCC1 in DNA repair Methods: We evaluated the presence of SNPs of these 6 genes and the survival of AHNCP treated with weekly paclitaxel, 80 mg/m2 iv for 6 weeks. Responding pts continue CHM till progression. All pts were cisplatin resistant and no other local therapies were available. We analysed paraffin-embedded biopsies from 47 consecutive AHNCP for SNPs of the mentioned genes. The status of the alleles wild type (wt) or at least 1 SNP was compared with response rate (RR), time to progression (TTP) and overall survival (OS) Results: Of 47 pts, 43 were male and 4 female. The median of age was 57 yr (46–80). RR was 45% (21/47) and the TTP in responders was 5 months of median. OS for all pts was 5.6 months. Wild type vs at least 1 SNPs frequencies according the genes were: CYP2C8 23/24; GSTT1 45/2; GSTP1 36/11; MDR1(A) 21/28; MDR1(B) 13/34; and ERCC1 27/20. OS was significantly better in pts with 2 or more SNPs accumulated (p=0.0455). No other significant differences were observed in RR, TTP or OS in SNPs vs wild type pts. Conclusions: SNPs of CYP2C8, MDR1(A) and MDR1(B) genes were more frequent than wt in our pts. OS was significantly better in pts with 2 or more SNPs accumulated. Paclitaxel provides high rate of responses of short duration in AHNC pts No significant financial relationships to disclose.

scholarly journals Single nucleotide polymorphisms in the HIF-1α gene and chemoradiotherapy of locally advanced rectal cancer

2012 ◽  
Vol 4 (5) ◽  
pp. 1056-1060 ◽  
Author(s):  
BIRGITTE MAYLAND HAVELUND ◽  
KAREN-LISE GARM SPINDLER ◽  
JOHN PLOEN ◽  
RIKKE FREDSLUND ANDERSEN ◽  
ANDERS JAKOBSEN
Keyword(s):  
Rectal Cancer ◽  
Single Nucleotide Polymorphisms ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Differentiation between wild-type and vaccines strains of varicella zoster virus (VZV) based on four single nucleotide polymorphisms

2017 ◽  
Vol 145 (12) ◽  
pp. 2618-2625
Author(s):  
L. JIN ◽  
S. XU ◽  
P. A. C. MAPLE ◽  
W. XU ◽  
K. E. BROWN
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Varicella Zoster Virus ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Single Nucleotide ◽  
Chain Reactions ◽  
Varicella Zoster ◽  
Polymerase Chain Reactions ◽  
Set Up ◽  
The Uk

SummaryVaricella–zoster virus (VZV) infection (chickenpox) results in latency and subsequent reactivation manifests as shingles. Effective attenuated vaccines (vOka) are available for prevention of both illnesses. In this study, an amplicon-based sequencing method capable of differentiating between VZV wild-type (wt) strains and vOka vaccine is described. A total of 44 vesicular fluid specimens collected from 43 patients (16 from China and 27 from the UK) with either chickenpox or shingles were investigated, of which 10 had received previous vaccination. Four sets of polymerase chain reactions were set up simultaneously with primers amplifying regions encompassing four single nucleotide polymorphisms (SNPs), ‘69349-106262-107252-108111’. Nucleotide sequences were generated by Sanger sequencing. All samples except one had a wt SNP profile of ‘A-T-T-T’. The sample collected from a patient who received vaccine 7–10 days ago, along with VZV vaccine preparations, Zostavax and Baike-varicella gave a SNP profile ‘G-C-C-C’. The results show that this method can distinguish vaccine-derived virus from wt viruses from main four clades, (clades 1–4) and should be of utility worldwide.

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