تأثير تعدد الأشكال الجينية لإنزيم استقلاب DPYD على فعالية عقار الـ Capecitabine في النساء المصابات بسرطان الثدي في العراق

Effect of Genetic Polymorphisms of DPYD metabolizing enzyme on Capecitabine Efficacy in Iraqi Breast Cancer Women

Background : Breast cancer is the major cause of cancer death in women living in industrialized countries. In Iraq, breast cancer ranked first as a cause of cancer mortality in women and is leading cause at the same time of death in the female population aged 30 to 54 years old. Dihydropyrimidine dehydrogenase (DPYD) gene’s product, a pyrimidine catabolic enzyme, is both the first step and the limiting one in the degradation of uracil and thymidine. Dihydropyrimidine dehydrogenase impairment is caused by mutations in this gene. The objective of study was to determine the association between breast cancer, the (G > A) (rs3918290) and of (rs55886062, T >G) polymorphisms of the DPYD gene, the haplotypes formed by them, and the serum concentrations of capecitabine and its active metabolite 5- flourouracuil (5FU) in postmenopausal women have breast cancer in Iraq,
Methods: The study was conducted on a total of 200 women, including 100 women without breast cancer who served as a control group aged range from (40-70years) and 100 women with breast cancer whose ages ranged from (45-75years), at the oncology center at Imam al-Hussain medical city in Kerbala, Iraq, were sorted into groups based on their age, body mass index, disease duration, and treatment length for this study, which was done between July 2022 and October 2022.
The concentration of capecitabine, the plasma levels of estradiol, carcinogenic type 15.3 (CA-15.3) and calcium were measured in 100 breast cancer patients who had been taking the drug for at least 3 months, all participants gave their informed consent. The determination of polymorphisms was performed by alelle specific PCR assay for two gene polymorphism (G > A) (rs3918290) and of (rs55886062, T > G) and that of drug concentration of capecitabine and Fluorouracil were calculated by high performance liquid chromatography (HPLC). Statistical analysis was performed with the SPSS and Haploview software.
Results: Serum blood concentrations of CA15.3, Capecitabine, and 5FU in breast cancer patients showed definite and significant variations, the polymorphism (G > A) (rs3918290). Results showed that their parameters concentration were significantly higher in Capecitabine, and 5FU in patients with the TT allele than in patients with the CC and CT alleles, and that it was significantly higher in Capecitabine and 5FU in patients with the CC allele than in patients with the AA and AC alleles in patients with DPYD*13 (rs55886062). The concentration of Fluorouracil was greater in patients with mutant alleles (p 0.001). The results showed a statistically significant increase (p 0.05) in the concentration of CA15.3 levels in women with breast cancer compared to the control group.
Conclusion: The presence of CA15.3, serum calcium, and estradiol in patient serum makes them potentially valuable novel diagnostic response biomarkers for patients with breast cancer due to their high levels of stability. Additionally, tumour markers, particularly CA15-3, may reflect the biological characteristics of tumours, and they may be useful prognostic indicators in cases of recurrent breast cancer, and genetic variation in DPYD metabolizing enzyme may be contributd to variability in efficacy to capacetabine therapy in asample of breast cancer Iraqi women besides variation in the incidence of adverse effects.