Detection of Cytochrome P450 Polymorphisms in Breast Cancer Patients May Impact on Tamoxifen Therapy

Document Type: Research Articles

Authors

1 Department of Pharmacology, Krishna University, Rajupeta, Machilipatnam, India.

2 Department of Pharmacology, Shri Vishnu College of Pharmacy, Bhimavaram, India.

3 Dr. MRAR PG Centre, Krishna University, Patha Pet, College Road, Nuzvid, India.

Abstract

Background: Breast cancer is the most common cancer among women worldwide. Tamoxifen (TAM), a selective
estrogen receptor modulator, is widely used in its treatment. TAM is metabolized by cytochrome P450 (CYP450) enzymes,
including CYP2D6, CYP3A5 and CYP2C19, whose genetic variations may have clinicopathological importance.
However, reports on the association of various P450 polymorphisms with certain cancers are contradictory. Methods:
We here investigated whether the prevalence of the four most common polymorphism in the CYP2D6*4 (G1934A),
CYP2D6*10 (C188T), CYP3A5*3 and CYP2C19*2 alleles has any link with breast cancer using genomic DNA and
polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. Results: Prevalences of
CYP2D6*4, CYP2D6*10 and CYP2C19*2 genotypes were differed significantly (P = 0.01 and P = 0.004) between
breast cancer patients and controls. The CYP3A5*3 genotype did not demonstrate statistically significant variation.
Conclusion: Polymorphisms in CYP2 appear to be associated with breast cancer risk. Our data taken together with
other reports indicates that drug resistance gene polymorphisms might be indicators of response to tamoxifen therapy
in breast cancer cases.

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