P-glycoprotein expression as a predictor of response to neoadjuvant chemotherapy in breast cancer.

BACKGROUND: Chemoresistance is an important factor determining the response of tumor to neoadjuvant chemotherapy (NACT). P-glycoprotein (P-gp) expression-mediated drug efflux is one of the mechanisms responsible for multi-drug resistance. Our study was aimed to determine the role of P-gp expression as a predictor of response to NACT in locally advanced breast cancer (LABC) patients. MATERIALS AND METHODS: P-gp expression was performed by real-time quantitative polymerase chain reaction [qRT-PCR] in 76 patients with LABC. Response to adriamycin-based regimen was assessed both clinically and with contrast enhanced computed tomography (CECT) scan before and after NACT. The significance of correlation between tumor and P-gp levels was determined with Chi-square test. RESULTS: Twenty-one had high and 55 had low P-gp expression. On analyzing P-gp expression with response by World Health Organization (WHO) criteria, statistical significance was obtained (P = 0.038). Similarly, assessment of P-gp expression with response by Response Evaluation in Solid Tumors (RECIST) criteria in 48 patients showed statistical significance (P = 0.0005). CONCLUSION: This study proves that P-gp expression is a determinant factor in predicting response to NACT. Finally, detection of P-gp expression status before initiation of chemotherapy can be used as a predictive marker for NACT response and will also aid in avoiding the toxic side effects of NACT in non-responders.

Association of aldosterone synthase (CYP11B2 C-344T) gene polymorphism & susceptibility to essential hypertension in a south Indian Tamil population.

Background & objective: Renin-angiotensin aldosterone system (RAAS) plays an important role in the regulation of blood pressure. Aldosterone, synthesized by aldosterone synthase in the adrenal cortex is encoded by the CYP11B2 gene. In this case-control study we examined the association between CYP11B2 C-344T polymorphism and essential hypertension in south Indian Tamil population. Methods: The study was conducted in 406 hypertensive cases and 424 healthy controls from Tamil population. Genotyping was performed by PCR-restriction fragment length polymorphism method. Statistical analysis was performed by logistic regression analysis. Results: The 344TT homozygous variant genotype (OR-1.8; 95% CI: 1.1-2.8; P=0.02) and T allele (P=0.007) were found to be significantly associated with hypertension. In gender based analysis, the risk was significantly higher in male hypertensives (OR-1.8; 95% CI: 1.0-3.6, P=0.05) but not in female subjects. Interpretation & conclusion: A significant association between CYP11B2 gene polymorphism and essential hypertension was observed and the risk was confined to male subjects in south Indian Tamil population.