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《Drug discovery today》2022,27(4):1108-1114
This project demonstrates the use of the IEEE 2791–2020 Standard (BioCompute Objects [BCO]) to enable the complete and concise communication of results from next generation sequencing (NGS) analysis. One arm of a clinical trial was replicated using synthetically generated data made to resemble real biological data and then two independent analyses were performed. The first simulated a pharmaceutical regulatory submission to the US Food and Drug Administration (FDA) including analysis of results and a BCO. The second simulated an FDA review that included an independent analysis of the submitted data. Of the 118 simulated patient samples generated, 117 (99.15%) were in agreement in the two analyses. This process exemplifies how a template BCO (tBCO), including a verification kit, facilitates transparency and reproducibility, thereby reinforcing confidence in the regulatory submission process. 相似文献
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Paul G. Richardson Fredrik Schjesvold Katja Weisel Philippe Moreau Larry D. Anderson Darrell White Paula Rodriguez-Otero Pieter Sonneveld Monika Engelhardt Matthew Jenner Alessandro Corso Jan Dürig Michel Pavic Morten Salomo Meral Beksac Albert Oriol Jindriska Lindsay Anna Marina Liberati Monica Galli Pawel Robak Alessandra Larocca Munci Yagci Filiz Vural Abraham S. Kanate Ruiyun Jiang Lara Grote Teresa Peluso Meletios Dimopoulos 《European journal of haematology》2022,108(1):73-83
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Amir FarmohammadiAli MomeniBanafshe BahmaniHossein GhorbaniRamin Ramzanpour 《Asian Pacific journal of cancer prevention》2020,21(1):255-258
Background: Paraoxonase 1 (PON1), a multifactorial antioxidant enzyme, has a defensive role against oxidative stress, which is believed to contribute to cancer development. This study aimed to investigate the association of PON1-L55M functional polymorphism with breast cancer risk. Material and methods: In the experimental study, blood samples were collected from 150 healthy women controls and 150 breast cancer subjects. The L55M genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. Results: Our analysis showed that the genotypes distribution is in Hardy-Weinberg equilibrium for both case and control groups. Our data revealed that there are significant associations between PON1-L55M polymorphism and breast cancer risk in homozygote (OR= 2.13, 95%CI= 1.14-4.00, p= 0.018), dominant (OR= 1.72, 95%CI= 1.07-2.76, p= 0.024), and allelic (OR= 1.55, 95%CI= 1.12-2.15, p= 0.008) models. Conclusions: Our results suggest that the PON1-L55M genetic variation could be a genetic risk factor for breast cancer risk and it could be considered as a molecular biomarker for screening of susceptible women. 相似文献
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Glutathione S-transferase Polymorphisms in Head and Neck Squamous Cell Carcinoma Treated with Chemotherapy and/or Radiotherapy 下载免费PDF全文
Mauricio Pereira ManigliaAnelise RussoPatrícia Matos Biselli-ChicoteJuliana Garcia de Oliveira-CucoloGabriela Helena Rodrigues-Flemingjosé Victor -ManigliaÉrika Cristina PavarinoEny Maria Goloni-Bertollo 《Asian Pacific journal of cancer prevention》2020,21(6):1637-1644
Background/Aim: The Glutathione S-transferases (GSTs) are important carcinogen-metabolizing enzymes. Polymorphisms involved in these enzymes can modulate the development and treatment of head and neck cancer. To investigate the association of GSTs polymorphisms with head and neck cancer and risk factors, clinical-pathological features, and survival time of the patients treated with chemotherapy and/or radiotherapy. Methods: The GST gene polymorphisms were evaluated in 197 cases and 514 controls by PCR-RFLP-Polymerase Chain Reaction Restriction Fragment Length Polymorphism. Results: The GSTP-313 was associated with a decreased risk for HNSCC (p=0.050). The GSTP1 haplotype analysis revealed a higher frequency of the AC and AT haplotypes in the case group than in the control group (p=0.013 and p=0.019, respectively), and the opposite for G-C haplotype (p = 0.015). Yet, the different combinations between the genotypes were associated with an increased risk of cancer. The study showed no association between the polymorphisms and primary tumor site, clinical-pathological characteristics, treatment (chemotherapy and/or radiotherapy) and survival time of the patients. Conclusion: The GST polymorphisms combination showed an increased risk for carcinogenesis, and studies with larger casuistry can contribute to the clarification of the role in individual patient differences for the response to chemotherapy and/or radiotherapy and identify biomarkers of susceptibility. 相似文献
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Valérie Boige Caroline Mollevi Sophie Gourgou David Azria Jean-François Seitz Marc Vincent Ludovic Bigot Beata Juzyna Isabelle Miran Jean-Pierre Gerard Pierre Laurent-Puig 《International journal of cancer. Journal international du cancer》2019,145(11):3163-3172
We examined whether 66 germline single-nucleotide polymorphisms (SNPs) in 10 candidate genes would predict clinical outcome in 316 patients with resectable locally advanced rectal cancer (LARC) enrolled in the ACCORD-12 phase III trial who were randomly treated with preoperative radiotherapy plus capecitabine (CAP45; n = 155) or dose-intensified radiotherapy plus capecitabine and oxaliplatin (CAPOX50; n = 161). The primary endpoint was tumor response according to the Dworak score. Multivariate logistic regression models adjusted on treatment arm and T stage determined the SNPs prognostic and predictive values for tumor response. In univariate analysis, five SNPs in ERCC2, XPA, MTHFR and ERCC1 were associated with the Dworak score in the CAPOX50 arm. In the overall population, interaction with treatment arm was significant for ERCC2 rs1799787 (pinteraction = 0.05) and XPA rs3176683 (pinteraction = 0.008), suggesting a predictive effect for response to oxaliplatin-based chemoradiotherapy (CRT). All but XPA rs3176683 had a prognostic effect on tumor response. In a multivariate model, interaction remained significant for XPA rs3176683 ([OR 7.33, 95% CI 1.40–38.23], pinteraction = 0.018) and the prognostic effect significant for ERCC2 rs1799787 ([OR 0.55, 95%CI 0.32–0.93], p = 0.027) and ERCC1 rs10412761 ([OR 0.57, 95%CI 0.34–0.98], p = 0.042). Patients with the T/G haplotype of rs1799787 and rs10412761 had a 60% decrease in odds of response (p < 0.001). None of the five SNPs were associated with toxicity, overall and disease-free survival. These data suggest that genetic variation in DNA repair genes influences response to preoperative CRT in LARC and identify patients who benefit from the addition of oxaliplatin to CRT. 相似文献
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《Clinical lung cancer》2020,21(2):171-176
BackgroundPatients with lung cancer continue to smoke owing to complex factors. Failure to quit smoking (defined as nicotine dependence) is significantly associated with genetic status. This study aimed to investigate the relationship between polymorphisms in nicotine dependence genes and smoking status after the diagnosis of lung cancer.Patients and MethodsA total of 240 patients with lung cancer were included from July 2017 to March 2018. According to the actual smoking condition after lung cancer diagnosis, eligible patients were divided into 3 groups: the never-smoking group, the failure to quit smoking group, and the successful smoking cessation group. Fagerstrom Test for Nicotine Dependence scores were used to evaluate the smoking status of each group. Three nicotine-dependent genes with 6 loci were detected.ResultsAmong the 240 patients, 86 were never-smokers, 51 failed to quit smoking, and 104 successfully quit smoking. The initial age of smoking in the failure to quit smoking group was significantly younger than those in the successful smoking cessation group (P = .001). There was a significant difference in the GG and AG and AA genotype distributions of CHRNA3 (rs578776) among the 3 groups (P = .003). There was also a significant difference in the distribution of CHRNA4 (rs2229959) genotypes among the 3 groups (P = .003). However, there was no significant difference in the genotype distribution of CHRNA5 (rs588765) among the 3 groups (P = .277).ConclusionsGene polymorphisms of CHRNA3 (rs578776) and CHRNA4 (rs1044396 and rs2229959) were associated with the success of smoking cessation after the diagnosis of lung cancer, which should be considered in the management of smoking cessation after patients are diagnosed with lung cancer. 相似文献