Current Pharmacogenomics and Personalized Medicine (Formerly Current Pharmacogenomics) - Volume 21, Issue 1, 2024

Background: The field of pharmacogenomics investigates the ways in which genes impact the body's reaction to drugs. Through the integration of genetics and medical knowledge, it is possible to develop individualised and efficient therapies that are based on genetic profiles. Specifically, this evaluation focuses on three aspects: 1) Finding molecular targets and gaining a grasp of their structures is the first step. 2) Using pharmacogenomics to lessen the harmful effects of drugs 1. 3) Predicting pharmacological mechanisms based on genetic variances. Methods: A systematic review examining pharmacogenomics' role in cancer chemotherapy, focusing on target molecules, drug resistance, and mechanism, was conducted using PRISMA-compliant databases. The review included English-published journals from 2000-2023, aiming to reduce bias and ensure all relevant research is found, chosen, and critically assessed. Results: The results show that over the past 20 years, cytotoxic medications and personalized treatments have significantly improved cancer treatment strategies. Targeted drugs, small molecule drugs, and pharmacogenomic biomarkers offer targeted treatment for carcinoma tissues. Conclusion: Understanding genetic profiles and drug resistance is crucial for effective cancer treatment. Combination therapies have advanced treatment for advanced or metastatic cancers.

Introduction: Prostate cancer is the second most frequent malignancy after lung cancer among men, accounting for 7% of new cancers diagnosed around the world (15% in developed regions). This disease has become more prevalent in Iran over the past few decades, moving up the rankings from 13th in 1986 to 4th in 2005 and finally reaching third place in a recent study in 2016. The purpose of this study is to investigate the association of rs10486567, rs13149290, rs6983267, and rs1545985 with prostate cancer predisposition in the Iranian population. Due to the genetic heterogeneity, each of the SNP should be studied separately in various communities. Material and Methods: This study was conducted as a case-control study on 200 patients referred to Hashminejad Hospital in Tehran. 103 men with prostate adenocarcinoma were selected as case, and 97 men with benign prostatic hyperplasia (BPH) were selected as control. In this research, according to FAVORGENE-Taiwan extraction kit instructions, genomic DNA was extracted from peripheral blood lymphocytes Tetra-primer ARMS-PCR method was used for SNP genotyping. Results: The significance level at the first stage was p-value≤0.4. rs10486567 (p-value = 0.802) and rs6983267 (p-value = 0.684). Based on the additive and multiplicative genetic model, no association of these polymorphisms with prostate adenocarcinoma was observed. As a result, rs10486567 and rs6983267 were removed at this stage. rs13149290 (p-value=0.4) and rs1545985 (p-value=0.4) at this stage were selected for the next stage. At the second stage rs13149290 (p-value=0.043) showed a significant difference in the comparison between the two groups, but this difference was not observed in relation to rs1545985 (p-value=0.392) rs1545985 was not associated with prostate adenocarcinoma in the additive genetic model. According to P=0.013 and OR (95% CI) =3.837 (1.306-11.268), rs13149290 polymorphism is associated with prostate adenocarcinoma in the additive genetic model (TT vs. CC). Conclusion: As a result of this study, it was observed that rs13149290 is associated with prostate cancer in the Iranian population. Also this polymorphism is associated with Gleason score=7 and PSA ≤4. Prostate cancer as an exposure effect is heterogeneous between different PSA levels. It is suggested that this polymorphism be investigated in a larger population and in each ethnic group separately.

Background: Clinical trial participants play a crucial role in advancing medical research, and the data generated from their participation can indeed be invaluable for future studies. However, the reuse of genetic or clinical research data comes with ethical challenges that need careful consideration. Here are some of the key ethical issues associated with the re-use of such data: Reusing data without clear informed consent raises issues of autonomy and respect for individuals' choices. Objective: The main aim of this study is to assess the understanding of individuals involved in clinical trials regarding the sharing of genetic research information. Moreover, it seeks to explore the ethical issues and benefits linked with the use of genetic research data for future research initiatives. Methods: A cross-sectional observational study was applied to assess Knowledge Attitude Practices of clinical trial participants on reuse of genetic research data. Results: The majority 70% of clinical trial participants were unsure about the difficulties that may arise in future regarding the re-use of genomic data, with concerns about confidentiality being the most common. Conclusion: The present study prioritized the involvement of clinical trial participants due to their critical role in both genetic and clinical research endeavors. There is a lack of awareness and understanding regarding the re-use of genetic research data and ethical issues among the trial participants. Researchers must take measures to de-identify or anonymize data to protect participants. There is a clear need for comprehensive awareness programs and guidelines aimed at all clinical trial stakeholders. These initiatives would ensure that researchers, participants, and other involved parties are well-informed and adhere to ethical standards when utilizing genetic data for subsequent research endeavors.

Aim: To analyse the nsSNPs associated with the human WWOX gene using bioinformatics tools. Background: WW domain-containing oxidoreductase (WWOX) is a protein-coding gene that controls several biological processes, including RNA splicing, transcription, and protein degradation. The modification in the WWOX gene is associated with osteopenia, metabolic syndrome, gestational diabetes, tumour progression, and disruption in lipid metabolism. Objective: The study focused on understanding the structural and functional distribution of high-risk nsSNPs of the WWOX gene using several bioinformatics tools. Methods: Retrieval of nsSNPs of WWOX gene from NCBI and Uniprot database. Identification of deleterious missense SNPs using the tools SIFT, Polyphen v2, PROVEAN, FATHMM, PhD-SNP, and SNPs & GO. The gene-gene and protein-protein interactions were investigated using GeneMANIA and STRING, respectively. The structural and functional characterisation of the gene was predicted using I-Mutant, MUPro, SOPMA, Alpha Fold, and NetPhos 3.1. Results: The study identified 7 out of 646 nsSNPs (rs193001955, rs200371768, rs370792938, rs2303192, rs371364838, rs372362643, rs374343152) as deleterious. The identified nsSNPs were destabilizing the WWOX protein. The secondary structure prediction indicated that the majority of the nsSNPs were random coil and alpha-helix. Meanwhile, phosphorylation was observed in several positions in threonine and serine residues, and the least phosphorylation was observed for tyrosine in the WWOX gene. Phosphorylation of high-risk variants of this gene may lead to alteration in the regulation of posttranslational modification. Conclusion: Our study predicted 7 functional nsSNPs that had detrimental effects on the structure and function of the WWOX gene. This will aid in the identification of candidate deleterious nsSNPs markers as a potential therapeutic target for disease diagnosis.