Impact of ERCC1 gene polymorphisms on response to cisplatin based therapy in oral squamous cell carcinoma (OSCC) patients
ML Avinash Tejasvi1, G Maragathavalli2, Uday Kumar Putcha3, M Ramakrishna4, R Vijayaraghavan5, CK Anulekha Avinash6
1 Department of Oral Medicine and Radiology, Kamineni Institute of Dental Sciences, Narketpally, Telangana, Ph.D Scholar (Oral Medicine and Radiology), Saveetha University, Chennai, Tamil Nadu, India
2 Department of Oral Medicine and Radiology, Saveetha Dental College and Hospitals, Chennai, Tamil Nadu, India
3 Department of Pathology and Microbiology, National Institute of Nutrition, Hyderabad, Telangana, India
4 Department of Radiation Oncology, MNJ Institute of Oncology and Regional Cancer Centre, Hyderabad, Telangana, India
5 Department of Research and Development, Saveetha University, Chennai, Tamil Nadu, India
6 Department of Prosthodontics, Kamineni Institute of Dental Sciences, Narketpally, Telangana, India
C K Anulekha Avinash
Professor, Department of Prosthodontics, Kamineni Institute of Dental Sciences, Narketpally, Nalgond, Telangana State
Source of Support: None, Conflict of Interest: None
Background and Objectives: Cisplatin is one of the major drugs that used in the treatment of oral cancer.Excision repair cross-complementation group 1 (ERCC1) is a key DNA repair gene in the nucleotide excision repair pathway which is activated in the repair of intra- and interstrand DNA crosslink caused by platinum-based treatment. The aim of this study was to investigate the association between polymorphisms in ERCC1 (C118T & C8092A) genes and the response to cisplatin-based chemotherapy.
Methods: ERCC1polymorphisms (C118T & C8092A) were studied using PCR-RFLP method from 150 OSCC patients as cases as well as 150 normal tissues from the same patients were collected as controls for this study. Results: Frequencies of ERCC1 C118C, C118T and T118T genotypes were 60%, 28% and 12% in OSCC patients and 78%, 19% and 3% in the controls, respectively. The C118T & T118T genotype had a 1.69 and 4.97 -folds increased risk for OSCC. Frequencies of ERCC1 C8092C, C8092A and A8092A were 78%, 18% and 4% in the OSCC patients and 89%, 10%, amd 1% in the controls, respectively. The C8092A genotype showed a 1.97-fold increased risk for OSCC.
Interpretation & Conclusions: In conclusion, this study highlights the DNA repair gene polymorphisms that might play a role in mediating susceptibility to oral squamous cell carcinoma and cisplatin therapy. Our data suggest that the ERCC1 C118T, T118T and ERCC1 C8092A genotypes are genetic risk factors for Oral squamous cell carcinoma and ERCC1 118 C/T and C8092A polymorphisms have significant influence on clinical outcome.