Association of CYP3A4*1B and CYP3A5*3 Genetic Polymorphisms with Lung Cancer and its Impact on Taxane Metabolism in Indian Population.

ABSTRACT

Background: The purpose of this study was to investigate the genotype frequencies of CYP3A4*1B and CYP3A5*3 in lung cancer patients which may be useful in determining the patients’ predisposition to platinum based therapies, and may be helpful for individualized drug dosing and improved therapeutics and disease management. Results: We evaluated these two common polymorphisms in south Indian population, based on case-control study of 126 lung cancer cases and 111 controls using a PCR-RFLP-based assay. The investigation of the CYP3A4*1B gene polymorphism revealed, no significant difference in distribution between the lung cancer patients and the controls (p=0.65) . The distribution of CYP3A5*3 homozygous genotypes and heterozygous plus homozygous genotypes were significantly associated (p=0.0004 & p=0.0001) with lung cancer patients, and the *3/*3 genotype had a 4.38 fold increased risk for lung cancer. In our study *1A/*1B heterozygous genotype patients were found to constitute a major percentage of patients receiving Gemcitabine plus carboplatin therapy. Conclusions: In conclusion, the results of our study indicated a relationship between CYP 3A4*1B and CYP3A5*3 polymorphisms and genetic predispositions to lung cancer. Thus detection of CYP3A4*1B/CYP3A4 and CYP3A5*3/CYP3A5 genotype frequencies in Indian population may be important in view of interindividualized drug dosing, improved therapeutics and disease management.