الفهرس 
LUNG CANCEROnly 14 pages are availabe for public view
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Abstract
L
ung cancer was assumed as a rare disease; now it’s considered a public health problem. It is one of the leading common causes of cancer-related deaths worldwide. In Egypt, lung cancer represents 5.0-7.0% of all cancers and ranks the fifth in males and in both sexes, and ninth among females.
The two main types of lung cancer include: non-small cell lung cancer and small cell lung cancer. The NSCLC is the major one representing about 85% of lung cancers. Approximately two thirds of patients with NSCLC are diagnosed at an advanced stage. Moreover, NSCLC is a chemo-resistant tumor. The prognosis for patients with NSCLC is dismal regardless of the chemotherapy regimen used.
Platinum-based chemotherapy is the standard treatment for most advanced NSCLC. Their clinical success is limited due to severe side effects and intrinsic or acquired resistance to the treatment.
Platinum salts bind to DNA forming DNA adducts which then inhibit DNA replication. DNA adducts of platinum are mainly removed by the nucleotide excision repair (NER) pathway. This is one of the four DNA repair mechanisms that has a role in the control of the progression of the cell cycle and apoptosis via DNA damage checkpoints.
The Excision Repair Cross Complementation group 1(ERCC1) gene is an important member of the nucleotide excision repair pathway that counteract the DNA damaging effect of chemotherapy and therefore may be associated with drug resistance.
The ERCC1 rs 11615 SNP impairs the activity of the nucleotide excision repair pathway and may affect the efficacy of platinum-based chemotherapy. Our study aimed to investigate the relationship between the ERCC1 gene polymorphism rs 11615 and the response to platinum-based chemotherapy in patients with NSCLC and the overall survival in order to prevent the non-necessary exposure to the toxic effect of chemotherapy.
The present study is a pilot cross-sectional study which was conducted on fifty (50) NSCLC patients who were recruited from the Oncology Clinic in Ain Shams University Hospitals; twenty (20) of them were responders to platinum-based chemotherapy and the other thirty (30) were non-responders according to the RECIST criteria. Detection of the ERCC1 11615 polymorphism by real-time PCR was done for both the responders’ and the non-responders’ groups.
Our study showed no statistically significant difference regarding the genotypic frequencies of the ERCC1 rs 11615 (T/C) polymorphism between the responders’ and the non-responders’ groups. Moreover, a non-significant association was observed between PFS and the genotypic variation of ERCC1 rs 11615.
CONCLUSION
I
n conclusion, our study did not confirm the presence of significant association between the ERCC1 rs 11615 polymorphism and the response to platinum-based chemotherapy. This collection of data might provide a useful platform for research and clinical health practice for the identification of molecular biomarkers that may affect the response to platinum-based chemotherapy.
RECOMMENDATIONS
– Further studies with larger sample size and longer follow up time are recommended to clarify the statistical significance of the association of the ERCC1 rs11615 gene polymorphism with the response to platinum-based chemotherapy and overall survival in NSCLC patients.
– Further studies are needed to investigate the predictive value of other functional SNPs in different DNA repair genes on the efficacy of platinum based-chemotherapy and monitor disease progression in NSCLC patients to integrate the genomic information of multiple markers.