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Genetic polymorphisms in candidate genes are not associated with increased vincristine-related peripheral neuropathy in Arab children treated for acute childhood leukemia: a single institution study.

OBJECTIVE: The aim of this study was to evaluate the potential association between candidate genetic polymorphisms and vincristine-related peripheral neuropathy in Arab children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: This is a retrospective evaluation of 133 Arab children treated for ALL at the Children's Cancer Center of Lebanon. Incidence and severity of, as well as the timing (in weeks) at which grade 2 or higher peripheral neuropathy occurred were recorded. Genotyping for ABCB1 (rs1045642), ABCB1 (rs1128503), ABCC2 (rs717620), CEP72 (rs924607), ETAA1 (rs17032980),

Report: Impact of drug combination of clopidogrel and pantoprazole In the prognosis of patients with transient ischemic attack.

The study aimed to investigate the impact of clopidogrel combined with proton pump inhibitors (PPI) pantoprazole treatment on the prognosis of patients with transient ischemic attack (TIA). A total of 478 cases of TIA patients treated with clopidogrel were randomly assigned half to clopidogrel combined with pantoprazole treatment and the control groups (clopidogrel treatment alone) from January 2012 to January 20l4. The platelet aggregation before and after treatment and cerebrovascular events incidence within 90 days were compared and analyzed. Multivariate analysis was used to estimate the i

CYP1A1 3801T>C polymorphism implicated in altered xenobiotic metabolism is not associated with variations in sperm production and function as measured by total motile sperm and fertilization rates with intracytoplasmic sperm injection.

OBJECTIVE: To evaluate the cytochrome P450 3801T>C polymorphism's frequency in relation to semen production, as determined by semen analysis parameters, and sperm function, as determined by fertilization rates with intracytoplasmic sperm injection (ICSI). DESIGN: Case-control study. SETTING: Academic-affiliated private practice. PATIENT(S): This study included patients undergoing IVF from 2004 to 2014 grouped into categories based on semen analysis parameters performed at a single andrology laboratory. Cases were patients with total motile sperm (TMS) counts of ≤20 × 10(6). Frequency-matche

Utility of a Systolic Blood Pressure Polygenic Risk Score With Chlorthalidone Response.

IMPORTANCE: The clinical utility of polygenic risk scores (PRS) for blood pressure (BP) response to antihypertensive treatment (AHT) has not been elucidated. OBJECTIVE: To investigate the ability of a systolic BP (SBP) PRS to predict AHT response and apparent treatment-resistant hypertension (aTRH). DESIGN, SETTING, AND PARTICIPANTS: The Genetics of Hypertension Associated Treatments (GenHAT) study was an ancillary pharmacogenomic study to the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT, which enrolled participants aged 55 years or older with

Derivation, Validation, and Prognostic Utility of a Prediction Rule for Nonresponse to Clopidogrel: The ABCD-GENE Score.

OBJECTIVES: The aim of this study was to develop a risk score integrating cytochrome P450 2C19 loss-of-function genotypes with clinical risk factors influencing clopidogrel response that would allow the identification with more precision of subjects at risk for high platelet reactivity (HPR) and adverse clinical outcomes. BACKGROUND: Clopidogrel is the most broadly used platelet P2Y12 inhibitor. However, a considerable number of patients achieve inadequate platelet inhibition, with persistent HPR, an established marker of increased thrombotic risk, underscoring the need for tools to help iden

DRD2 co-expression network and a related polygenic index predict imaging, behavioral and clinical phenotypes linked to schizophrenia.

Genetic risk for schizophrenia (SCZ) is determined by many genetic loci whose compound biological effects are difficult to determine. We hypothesized that co-expression pathways of SCZ risk genes are associated with system-level brain function and clinical phenotypes of SCZ. We examined genetic variants related to the dopamine D2 receptor gene DRD2 co-expression pathway and associated them with working memory (WM) behavior, the related brain activity and treatment response. Using two independent post-mortem prefrontal messenger RNA (mRNA) data sets (total N=249), we identified a DRD2 co-expres

A large-scale genome-wide association study meta-analysis of cannabis use disorder.

BACKGROUND: Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50-70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. METHODS: To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iP

Vitamin D in Type 2 Diabetes: Genetic Susceptibility and the Response to Supplementation.

Variants of vitamin D metabolism-genes may predispose to type 2 diabetes (T2D). This study investigated the impact of these variants on disease susceptibility, Vitamin D, parathyroid hormone, C-peptide and HbA1c levels before and after cholecalciferol supplementation in patients with T2D.Twelve polymorphisms within CYP2R1, CYP27B1, DBP, VDR and CYP24A1 were genotyped in 553 T2D patients and 916 controls. In addition 65 patients receiving either cholecalciferol or placebo were analyzed during 6 months intervention and 6 months follow-up.T2D risk alleles are VDR rs7975232 "G" (pc=0.031), rs15444

Pharmacogenomics and Big Data in medical oncology: developments and challenges.

Medical oncology, through conventional chemotherapy as well as targeted drugs, remains an important component of cancer patient management, particularly for systemic disease. Despite advances in all areas of medical oncology, certain challenges persist in the form of drug resistance and severe normal tissue toxicity. These unwanted effects can be counteracted through a patient-tailored treatment approach, which in chemotherapy is translated as pharmacogenomics. This research field investigates the way genetic makeup influences a patient's response to various drugs with the aim to minimize tria

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… Results lacked conclusiveness due to the mixed evidence concerning the value of genetic testing for cancer treatment guidance and owing to the fact that pharmacogenomics testing is a dominant strategy in only a limited number of studies. … Providers’ perspectives on the clinical utility of pharmacogenomic testing in pediatric patients . Pharmacogenomics 2021 ; 22 ( 5 ): 263 – 274 . 33657875 10.2217/pgs-2020-0112 PMC8050981 89 Avello K Bell M Stein Q , et al . …

Why pharmacogenomic biomarkers for chemotherapy-induced peripheral neuropathy fail: a systematic review of genetic associations, replication, and clinical translation.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting toxicity of cancer treatment, yet reliable biomarkers to predict individual susceptibility remain lacking. Germline genetic variation has been widely investigated as a potential contributor to CIPN risk; however, the consistency and clinical utility of these associations remain unclear. We performed a systematic review of genetic association studies evaluating CIPN across neurotoxic chemotherapies. PubMed, Embase, Web of Science, and the Cochrane Library were searched (April 2025) for human studies assessing germline

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… Despite extensive investigation, the lack of robust, reproducible associations limits the utility of pharmacogenomic testing in guiding treatment decisions or identifying high-risk patients. To overcome these limitations, future studies must adopt more rigorous and standardised approaches. …

The effects of OPRM1 118A>G on methadone response in pain management in advanced cancer at end of life.

Cancer pain is the most feared symptom at end of life. Methadone has advantages over other opioids but is associated with significant variability in clinical response, making dosing challenging in practice. OPRM1 is the most studied pharmacogene associated with the pharmacodynamics of opioids, however reports on the association of the A118G polymorphism on opioid dose requirements are conflicting, with no reports including methadone as the primary intervention. This association study on OPRM1 A118G and response to methadone for pain management, includes a review of this genetic factor's role i

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… As the technology in pharmacogenomic testing becomes more accessible and economical 4 , clinicians will be faced with having patients’ genotypes available even if they have not explicitly ordered a test with a specific drug in mind. …

Exploiting artificial intelligence in precision oncology: an updated comprehensive review.

Precision oncology considers the genetic makeup of both the tumor and the cancer patient, medical history, clinical metadata, lifestyle and environmental factors. Thus, adoption of precision cancer medicine mandates sophisticated integrative analysis. Being a master in sorting and solving the puzzle pieces, artificial intelligence (AI)-powered frameworks emerged to fill the gap via executing multimodal analysis and generating meaningful outputs. Herein, we systematically discussed the opportunities and challenges of exploiting AI-assisted models in preclinical cancer research and in clinical o

Using Genomic Data in Personalized Oncology Medicine: An Exploratory Expert-Elicitation Study with Narrative Regulatory Mapping of Regulations, Implementations, and Challenges in Saudi Arabia.

BACKGROUND/OBJECTIVES: Personalized medicine represents a transformative approach to healthcare in Saudi Arabia. However, a significant research gap exists regarding the specific regulatory, implementation, and practical challenges of integrating genomic data into personalized oncology care in the Saudi context. We aimed to conduct an exploratory assessment of the current regulatory landscape, practices, and challenges related to genomic data use in personalized oncology in Saudi Arabia and to identify regulatory and practical gaps, propose actionable solutions, and outline future directions f

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… Additionally, the training of healthcare providers varies depending on hospital-specific programs and individual experiences with pharmacogenomic testing. Figure 1 Human Cancer Genomic Research (HCGR) laboratory at King Faisal Specialist Hospital & Research Centre. … testing in Saudi oncology centers. …

Association of KCNJ6 rs2070995 and methadone response for pain management in advanced cancer at end-of-life.

Opioids are the therapeutic agents of choice to manage moderate to severe pain in patients with advanced cancer, however the unpredictable inter-individual response to opioid therapy remains a challenge for clinicians. While studies are few, the KCNJ6 gene is a promising target for investigating genetic factors that contribute to pain and analgesia response. This is the first association study on polymorphisms in KCNJ6 and response to methadone for pain management in advanced cancer. Fifty-four adult patients with advanced cancer were recruited across two study sites in a prospective, open lab

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… As the technology in pharmacogenomic testing becomes more accessible and economical, the ability for pain management therapy to be guided by precision genomic information provides a promising area for improving quality of life in palliative care. …

Machine learning in onco-pharmacogenomics: a path to precision medicine with many challenges.

Over the past two decades, Next-Generation Sequencing (NGS) has revolutionized the approach to cancer research. Applications of NGS include the identification of tumor specific alterations that can influence tumor pathobiology and also impact diagnosis, prognosis and therapeutic options. Pharmacogenomics (PGx) studies the role of inheritance of individual genetic patterns in drug response and has taken advantage of NGS technology as it provides access to high-throughput data that can, however, be difficult to manage. Machine learning (ML) has recently been used in the life sciences to discover

Leveraging stories of cardiac amyloidosis patients of African ancestry or descent to support patient-derived data elements for efficient diagnosis and treatment.

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Precision medicine and monoclonal antibodies: breach of promise?

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Long-Term Effects of Pediatric Acute Lymphoblastic Leukemia Chemotherapy: Can Recent Findings Inform Old Strategies?

During the last few decades, pediatric acute lymphoblastic leukemia (ALL) cure rates have improved significantly with rates exceeding 90%. Parallel to this remarkable improvement, there has been mounting interest in the long-term health of the survivors. Consequently, modified treatment protocols have been developed and resulted in the reduction of many adverse long-term consequences. Nevertheless, these are still substantial concerns that warrant further mitigation efforts. In the current review, pediatric-ALL survivors' late adverse events, including secondary malignant neoplasms (SMNs), car

Molecular Classification and Pharmacogenetics of Primary Plasma Cell Leukemia: An Initial Approach toward Precision Medicine.

Primary plasma cell leukemia (pPCL) is a rare and aggressive variant of multiple myeloma (MM) which may represent a valid model for high-risk MM. This disease is associated with a very poor prognosis, and unfortunately, it has not significantly improved during the last three decades. New high-throughput technologies have allowed a better understanding of the molecular basis of this disease and moved toward risk stratification, providing insights for targeted therapy studies. This knowledge, added to the pharmacogenetic profile of new and old agents in the analysis of efficacy and safety, could

Genetic Polymorphisms Associated with Vincristine Pharmacokinetics and Vincristine-Induced Peripheral Neuropathy in Pediatric Oncology Patients.

Vincristine (VCR) is an important component of curative chemotherapy for many childhood cancers. Its main side effect is VCR-induced peripheral neuropathy (VIPN), a dose limiting toxicity. Some children are more susceptible to VIPN, which is at least partially dependent on genetic factors and pharmacokinetics (PK). In this study, we identify and replicate genetic variants associated with VCR PK and VIPN. Patient samples from a randomized clinical trial studying the effect of administration duration of VCR on VIPN in 90 patients were used. PK sampling was conducted on between one and five occas