DNA-Repair Gene Polymorphisms Predict Favorable Clinical Outcome Among Patients With Advanced Squamous Cell Carcinoma of the Head and Neck Treated With Cisplatin-Based Induction Chemotherapy
| العنوان: | DNA-Repair Gene Polymorphisms Predict Favorable Clinical Outcome Among Patients With Advanced Squamous Cell Carcinoma of the Head and Neck Treated With Cisplatin-Based Induction Chemotherapy |
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| المؤلفون: | Luis Manso, Soledad Gamarra, Pedro P. Medina, Ricardo Hitt, Miguel Quintela-Fandino, Hernán Cortés-Funes, Montserrat Sanchez-Cespedes |
| المصدر: | Journal of Clinical Oncology. 24:4333-4339 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2006. |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Male, Oncology, Cancer Research, Pathology, DNA Repair, Glutamine, Polymerase Chain Reaction, XRCC1, Gene Frequency, Antineoplastic Combined Chemotherapy Protocols, Genotype, Medicine, Prospective Studies, Aged, 80 and over, Alanine, DNA, Neoplasm, Middle Aged, Prognosis, DNA-Binding Proteins, Treatment Outcome, Epidermoid carcinoma, Head and Neck Neoplasms, Carcinoma, Squamous Cell, Female, Asparagine, Polymorphism, Restriction Fragment Length, medicine.drug, Adult, medicine.medical_specialty, DNA repair, Single-nucleotide polymorphism, Arginine, Polymorphism, Single Nucleotide, Predictive Value of Tests, Internal medicine, Carcinoma, Humans, Cysteine, Aged, Neoplasm Staging, Proportional Hazards Models, Xeroderma Pigmentosum Group D Protein, Cisplatin, Aspartic Acid, business.industry, Lysine, Endonucleases, medicine.disease, Survival Analysis, X-ray Repair Cross Complementing Protein 1, Multivariate Analysis, ERCC1, business |
| الوصف: | Purpose Cisplatin kills tumor cells through DNA cross linking. Alterations in the function of DNA repair genes may affect DNA repair proficiency and influence cancer patients' response to cisplatin. We studied whether single nucleotide polymorphisms (SNPs) of DNA repair genes predict the response to cisplatin or prognosis in patients with squamous cell carcinoma of the head and neck (SCCHN). Methods A polymerase chain reaction–restriction fragment length polymorphism (RFLP) approach was used to determine the frequency of the SNPs: XPD-Asp312Asn, XPD-Lys751Gln, ERCC1-C8092A, and XRCC1-Arg399Gln in DNA from peripheral lymphocytes of 103 stage IV SCCHN patients. Results The frequencies of the distinct genotypes were, respectively, for the homozygous common allele, heterozygous and homozygous polymorphic variant: 53%, 40%, and 7% for ERCC1; 50%, 42%, and 8% for XPD-312; 35%, 57%, and 8% for XPD751; and 35%, 51%, and 13% for XRCC1. Patients with only common alleles at all the SNPs tested had a median overall survival of 5.1 months (range, 4.3 to 6.0 months) as compared with not reached for patients with at least one polymorphic variant (P < .001). Estimates from Cox's multivariate analysis suggest that the accumulation of each polymorphic variant decreases the probability of dying by a factor of 2.1 (P < .001; the presence of seven polymorphic variants confers a 175-fold protection). The accumulation of polymorphic variants increases by 2.94-fold the probability of achieving a complete response to treatment (P = .041). Conclusion Using a multivariate model, the presence of polymorphic variants in DNA-repair genes are powerful prognosis factors and response to cisplatin predictors among SCCHN patients. |
| تدمد: | 1527-7755 0732-183X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::739996965a09d4d73e174012b4dcea86Test https://doi.org/10.1200/jco.2006.05.8768Test |
| رقم الانضمام: | edsair.doi.dedup.....739996965a09d4d73e174012b4dcea86 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
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