دراسة تأثير تعدد النمط الجيني لجين ABCB1 مع الاستجابه السريريه لعقار الباكليتاكسيل في النساء المصابات بسرطان الثدي في كربلاء

Study The Impact of The ABCB1 Gene Polymorphism On Clinical Outcomes of Paclitaxel Monotherapy in Women With Breast Cancer in Kerbala

Abstract
Background Breast cancer is defined as a disordered growth of cells from any of the tissues of the mammary gland (ducts or lobules) with the ability to spread, It is considered the most common cancer among women in both developed and non developing countries, wo. CA15.3 is an indicator of tumor response to treatment, which allows early identification of recurrence and adjustment of Paclitaxel treatment. In this sense, pharmacogenetics plays a fundamental role in understanding the individual factors that modify the response to breast cancer treatment, particularly the study of genes involved in the of Paclitaxel chemotherapy transporting . In this case, those of the A BCB1 3435G>A (rs1045642) and 2677G>A (rs2032582) pathway. The aim of study was to investigate of ABCB1gene polymorphism with two SNPs 3435G>A (rs1045642) and 2677G>A in postmenopausal women with breast cancer in Iraq as well as ABCB1gene polymorphism on paclitaxel efficacy and association between paclitaxel induce peripheral neuropathy and response.
Methods: This study included 100 patients (45-75 years) with a clinical diagnosis of breast cancer who were going to start (paclitaxel) chemotherapy . The able to identify genetic variants and their association with main adverse effect of this drug, as well as to complete neurological response in patients with chemotherapy treated Patients at the oncology center at Imam al-Hussain medical city in Kerbala, Iraq, who sorted into groups based on their postmenopausal age, disease duration, and treatment long for this study, which was done between July 2022 and december 2022 for sample collection, The efficacy of Paclitaxel, serum concentrations of (Estradiol and CA 15.3) were measured in women with breast cancer who had been taking the drug, forms of informed consent with participants’ signatures were collected from everyone. The determination of polymorphisms was performed by Allele-Specific PCR assay for two gene polymorphism 3435G>A (rs1045642) and of 2677G> A (rs2032582), and serum concentration of paclitaxel was measured by high performance liquid chromatography.
Results: The study found that patients with CA15-3 > 30 U/mL are at risk of non-responses compared to those with CA15-3< ( 30 U/mL). The findings demonstrated a statistically significant low in the amount of CA 15-3 found in breast cancer patients response (22.45± 9.28) group in comparison to the level found in the non-response (86.93 ± 11.34) group for patients who received Paclitaxel chemotherapy. There is a significant decrease in CA 15-3 levels with a significant increase in neuropathy score.it found reverse negative correlation value (-0.821) between concentration of CA15.3 and grade score of peripheral neuropathy in response to paclitaxel treatment. Also we found that ABCB1 gene highly polymorphism and two snips 3435G>A (rs1045642) . Patients with allele GG in their chromosomes respond better (15.56±6.89) than those with alleles AA and GA, as well as patients with the allele GG of the 2677G>A (rs2032582)that had a greater response to treatment (195.17±14.68) compared to those with the alleles AA and GA.
Conclusion: According to the findings of the study,ABCB1is highly polymorphism and in breast cancer women in Iraq .There is a substantial connection between two SNPs ABCB1 3435G>A (rs1045642) and 2677G>A (rs2032582) with paclitaxel efficacy. The incidence of peripheral neuropathy is the main adverse effect of Paclitaxel chemotherapy in women have breast cancer that have better response according to low Ca 15.3 . continuous ,effective measurement and close follow up are required to control situation.