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[9005153.] رقم البحث : 9005153 - |
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PREVALENCE OF CYP2D6*4 AND ITS POSSIBLE RELATION TO THERAPEUTIC OUTCOMES OF ADJUVANT TAMOXIFEN THERAPY IN EGYPTIAN PREMENOPAUSAL WOMEN WITH BREAST CANCER / انتشار انزيم سيتوكروم 2 دي 6*4 وعلاقته المحتملة بالنتائج العلاجية لعقار التاموكسيفين المساعد لدى النساء المصريات المصابات بسرطان الثدي في مرحلة قبل انقطاع الطمث |
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قطاع الدراسات الصيدلية / الفارماكولوجى |
| تخصص البحث : الفارماكولوجى |
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Bulletin of Pharmaceutical sciences / |
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سارة يوسف محمد ( Sarahyousef30@yahoo.com - ) |
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د/ أميرة فوزي طه - مؤلف رئيسي |
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الفارماكولوجى |
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Background: Although tamoxifen is a main adjuvant therapy in estrogen positive breast cancer especially in premenopausal women, reliance on genetic polymorphisms of its CYP2D6 metabolizing enzyme and/or therapeutic drug monitoring of its active metabolite, endoxifen to determine tamoxifen-therapeutic outcomes is debatable. Objective: The goal of the study was to investigate the prevalence of CYP2D6*4 and possible association between its nonfunctional allele (A) and both tamoxifen-induced adverse effects and cancer relapse in premenopausal breast cancer patients. Method:Polymerase chain reaction -restriction fragment length polymorphism (PCR-RFLP) analysis was applied for detection of CYP2D6*4 (1846 G>A) genotypes. Results:Genotyping analysis of CYP2D6*4 showed a minimal allele frequency of 23%. Increased endometrial thickness in mm was significantly correlated with CYP2D6*4 GA and AA genotypes in comparison with GG genotypes (P< 0.01). No other relations were found between CYP2D6*4 alleles and other tamoxifen adverse effects (P > 0.9) or cancer relapse (P= 0.7). Conclusion: The prevalence of CYP2D6*4 polymorphism in Egyptian premenopausal females with breast cancer who are given tamoxifen is similar to that in Caucasians. The nonfunctional allele (A-allele) of CYP2D6*4 showed a significant association with increased endometrial thickness possibly related to tamoxifen, but no association with other drug adverse effects or cancer relapse. |
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