Biomarkers as Valuable tools in Clinical Diagnostics
Kaiser Jamil, Director, Jawaharlal Nehru Institute of Advanced Studies
Biomarkers in breast cancer have long been known and aberrations in BRCA1 or BRCA2 and CCNE1 for breast cancer and ovarian cancer modulate survival rates. Advanced ovarian cancer patients who achieve an excellent response to primary platinum-based chemotherapy with a cancer antigen 125 (CA-125) serum level less than 10 U/mL were more amenable to the benefits of paclitaxel maintenance therapy. Biomarkers can be valuable tools in clinical diagnostics as well as in therapeutic discovery and development. They are useful to predict response to therapy or risk of side effects for personalized medicine applications. Various types of biomarkers include predisposition, screening, diagnostic, prognostic, toxicity, suceptible and resistant biomarkers. In our study working with lung cancer patients, we examined the role of MDR1 C3435T polymorphisms in lung cancer patients undergoing chemotherapy. Frequencies of MDR1 C3435C, C3435T and T3435T genotypes were 61, 16 and 23 % in lung cancer patients and 86, 9 and 5 % in the controls, respectively as determined by PCR-RFLP. We also correlated the association between MDR1 genotypes with different combinations of chemotherapy. The combinations and genotype distributions in the group receiving paclitaxel and cisplatin were as follows: CC (67 %), CT (24 %) and TT (9 %) genotypes, respectively, and the group receiving carboplatin and gemcitabine were CC (46 %), CT (19 %) and TT (35 %) genotypes, respectively. We found that MDR1 (rs1045642) C3435T polymorphism and gene expression was significantly associated with the clinical outcome in lung carcinoma patients This is the first study to determine, quantitatively, expression of the MDR1 gene in lung carcinoma. MDR1 C3435T polymorphism and its expression were significantly associated with the clinical outcome and can be used as a genetic marker.
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