Cisplatin (CDDP) combined with radiotherapy (RT) is employed in head and neck squamous cell carcinoma (HNSCC) with variable toxicities and clinical response. Glutathione S-transferases (GSTs) participate in CDDP excretion from cells, and genes encoding GSTs, GSTM1, GSTT1and GSTP1, are polymorphic in humans. This prospective study aimed to evaluate the roles of GSTM1, GSTT1, and GSTP1 Ile105Val polymorphisms in outcomes of HNSCC patients treated with CDDP chemoradiation. Ninety patients were genotyped by multiplex PCR. Urinary CDDP measurements were performed by HPLC. Treatment side effects and response were analysed by conventional criteria. Patients with GSTT1 genes showed 7.23- and 5.37-fold higher likelihood of presenting vomiting and ototoxicity, lower glomerular filtration rate (GFR), and lower elimination of CDDP in urine relative to patients with deleted genes. Patients harbouring the GSTP1 IleVal or ValVal genotypes showed 4.28-fold higher likelihood of presenting grade 2 or 3 vomiting and lower GFR with treatment than those harbouring the IleIle genotype. In multivariate Cox analysis, patients with the GSTP1 105ValVal genotype had 3.87 more chance of presenting disease progression than those with the IleIle or IleVal genotype (p < 0.01). Our findings provide preliminary evidence that inherited abnormalities in CDDP metabolism, related to GSTT1 and GSTP1 Ile105Val polymorphisms, alter outcomes of HNSCC patients treated with CDDP and RT.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597539 | PMC |
| http://dx.doi.org/10.1038/s41598-019-45808-6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Investigation of Genetic Polymorphisms Related GSTM1, GSTT1, GSTP1 Genes and their Association with Radiotherapy Toxicity among Head and Neck Cancer Patients.
Asian Pac J Cancer Prev
January 2025
Department of Molecular Biology & Genetics, Krishna Institute of Allied Sciences, Krishna Vishwa Vidyapeeth "Deemed to be University", Taluka-Karad, Dist- Satara, Pin-415 539, (Maharashtra) India.
Background: In this study we explored the association of polymorphisms of glutathione s transferase gene including GSTM1, GSTT1 and GSTP1 with adverse acute normal tissue reactions resulted from radiotherapy in HNC patients. We assessed the association of GSTM1 and GSTT1 null genotypes and Ile105Val of exon-5 and Ala114Val of exon-6 of GSTP1 gene polymorphisms with the risk of acute skin toxicity reactions after therapeutic radiotherapy in HNC patients.
Methods: Four hundred HNC patients administered with Intensity modulated radiation therapy were enrolled in this study for the evaluation of radiotherapy associated toxicity reactions.
Response to azathioprine treatment in autoimmune hepatitis is dependent on glutathione transferase genotypes.
Dig Liver Dis
January 2025
Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Department of Laboratory Medicine, Region Jönköping County, Jönköping, Sweden. Electronic address:
Background: Azathioprine (AZA) is part of the standard treatment for autoimmune hepatitis (AIH). The first step in the complex bioconversion of AZA to active metabolites is mediated by glutathione transferases (GSTs).
Aims: Elucidate the association between GSTM1 and GSTT1 copy number variation (CNV), genetic variation in GSTA2, GSTP1, and inosine-triphosphate-pyrophosphatase, and the response to AZA in AIH.
Characterization of NAT, GST, and CYP2E1 Genetic Variation in Sub-Saharan African Populations: Implications for Treatment of Tuberculosis and Other Diseases.
Clin Pharmacol Ther
January 2025
Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Tuberculosis (TB) is a major health burden in Africa. Although TB is treatable, anti-TB drugs are associated with adverse drug reactions (ADRs), which are partly attributed to pharmacogenetic variation. The distribution of star alleles (haplotypes) influencing anti-TB drug metabolism is unknown in many African populations.
View Article and Find Full Text PDFMolecular Approach of Oxidative Stress and Bronchopulmonary Dysplasia: Relationship of GSTM1 and GSTT1 Genes.
Med Princ Pract
January 2025
Surgical Specialties Department, School of Medicine of São José of Rio Preto (FAMERP), São José of Rio Preto, Brazil.
Bronchopulmonary dysplasia (BPD) is a chronic lung disease, with its own clinical, radiological, and histopathological characteristics, which mainly affects premature newborns (NBs), resulting from a combination of factors that include immaturity, inflammation, and lung injury, in addition to therapy with mechanical ventilation and exposure to high concentrations of oxygen. However, even with advances in care for critically ill NBs, BPD continues to be a challenge for the care team and family members. This has been identified as one of the most important causes of morbidity and mortality due to prematurity and can have significant impacts on the quality of life of the affected patients.
View Article and Find Full Text PDFThe association between the Glutathione S-transferase polymorphisms and addiction to opioids and methamphetamine in the Iranian population.
Front Psychiatry
December 2024
Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran.
Introduction: Glutathione S-transferase (GST) has the ability to detoxify the cellular environment of xenobiotic compounds and by-products of oxidative stress. The expression levels of GST genes and their polymorphisms are associated with various human diseases. Methamphetamine and opiate addiction also account for a significant proportion of SUDs in Iran.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!