Genetic Polymorphic Impact of Metabolizing Enzyme (CYP3A4 and UGT1A4 genes) on Anastrazole Response in Iraqi Breast Cancer Women

1.1. Background and Objective: Anastrazole is an aromatase inhibitor used widely in therapy of breast cancer and has been metabolized by CYP3A4 and UGT1A4 in liver. Breast cancer is the most common cancer type in worldwide and the second causes of death after lung cancer and the one of therapy that use in its treatment is aromatase inhibiter, anastrazole has been indicated CYP3A1 and UGT1A4 are the main metabolizing enzyme, so the interindividual variation in anastrazole response are due to polymorphism of these gene. We have aimed to determine whether CYP3A4*22 and UGT1A4*2 single nucleotide polymorphisms can have affected on the response of anastrazole. 1.2. Method: 100 Iraqi females with hormone positive breast cancer were included in this study. patients were genotyped for SNPs in the CYP3A1 and UGT1A4 genes to research for response to anastrazole thought measured serum level of estradiol (E2) and tumor marker CA15.3. Highly polymorphic CYP3A4*22 (rs35599367) and UGT1A4*2 (rs6755571) were detected with different genotypes in variable percentage in Iraqi breast cancer women. 1.3. Results: For rs35599367 found that the wild genotype(GG) and for rs6755571 the mutant genotype (TT) were most abounded in 100 breast cancer women and also (AA) another mutant genotype of rs6755571 detected but in low percent. Non –significant association between different detected genotype of both SNPs and serum estradiol level, elevation of serum CA15.3 level and development of arthralgia. 1.4. Conclusion: Both SNPs suggesting had no effect on the serum levels of E2 and CA15.3 and development of arthralgia.