[Genetic background of cisplatin induced ototoxicity].

نویسندگان

  • M Jurajda
  • T Talach
  • R Kostřica
  • R Lakomý
  • I Kocák
  • M Cvanová
چکیده

BACKGROUND Cisplatin induced ototoxicity is a serious adverse effect of cisplatin therapy. Cisplatin induced ototoxicity shows significant interindividual variability. This variability is probably based on genetic background. Recent papers describe association of cisplatin ototoxicity with allelic variants of glutathion-S-transferase coding genes. PATIENTS AND METHODS We have analyzed 55 patients treated with cisplatin therapy without any previous hearing impairment. Audiometric examination was performed before the start of cisplatin therapy and then before and after each cycle of cisplatin. DNA isolated from peripheral blood samples was used to analyze genetic polymorphisms of selected genes coding for glutathion-S-transferases. RESULTS We have demonstrated association of early onset of cisplatin induced hearing impairment with absence of null allele of GSTT1 (p = 0.009). Both GSTM1 gene deletion and single nucleotide polymorphism in GSTP1 gene (rs1695) did not show any association with cisplatin induced ototoxicity. CONCLUSION Early onset of cisplatin induced hearing impairment is more probable in persons with two functional alleles of GSTT1 gene.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Cisplatin-induced ototoxicity in pediatric solid tumors: the role of glutathione S-transferases and megalin genetic polymorphisms.

Cisplatin-induced ototoxicity, an important dose-limiting side effect, has proven high interindividual variability. Glutathione S-transferases (GSTs) are isoenzymes involved in cellular detoxification processes. Megalin has been demonstrated to bind aminoglycosides, known to be similar to cisplatin for their ototoxicity. The GSTs and megalin expression is genetically polymorphic, which might be...

متن کامل

A Dose-Effect Study of Cisplatin Ototoxicity in Albino Guinea Pigs

Introduction: Cisplatin is one of the most commonly used antineoplastic drugs; nonetheless, its ototoxic dose-limiting side effects have remained a significant challenge in clinical practice. The recognition of the exact template of hearing loss induced by multiple low doses of cisplatin could be of great help in managing the treatment process. The present study aimed to investigate the e...

متن کامل

Analysis of Cisplatin-Induced Ototoxicity Risk Factors in Iranian Patients with Solid Tumors: a Cohort, Prospective and Single Institute Study

Background: Cisplatin has been associated with irreversible hearing damage. Up to now, there is no therapeutic intervention showing benefit in preventing Cisplatin-induced ototoxicity. The aim of this study was to determine risk factors contributing to hearing impairment after cisplatin administration in Iranian patients. Methods: Hearing thresholds of 124 patients before and after cisplatin ad...

متن کامل

Reversible p53 inhibition prevents cisplatin ototoxicity without blocking chemotherapeutic efficacy

Cisplatin is a widely used chemotherapy drug, despite its significant ototoxic side effects. To date, the mechanism of cisplatin-induced ototoxicity remains unclear, and hearing preservation during cisplatin-based chemotherapy in patients is lacking. We found activation of the ATM-Chk2-p53 pathway to be a major determinant of cisplatin ototoxicity. However, prevention of cisplatin-induced ototo...

متن کامل

Downstream Targets of Lmo4 Are Modulated by Cisplatin in the Inner Ear of Wistar Rats

Lmo4, a transcriptional regulator, appears to be a key player in mediating the cochlear pathology in cisplatin ototoxicity, as it controls cellular responses by modulating the formation of transcriptional complexes. We provided the first evidence of in vivo nitration of Lmo4 in cisplatin ototoxicity. Our data suggested that nitration of Lmo4 and associated decrease in its cochlear expression ha...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti

دوره 25 3  شماره 

صفحات  -

تاریخ انتشار 2012