The Influence of genetic polymorphism in GSTP1 and ABCB1 genes on cyclophosphamide/doxorubicin- related myelosuppression in Indonesian Patients.
The Cyclophosphamide/Doxorubicin chemotherapy is a common cytotoxic medication used in neoadjuvant breast cancer treatment. Patients often experience myelosuppression. As a side effect of the treatment, it was known to have caused increased morbidity , mortality , treatment cost and affect the quality of life.
Currently, the variety of response and severity of side effect often related to the genetic polymorphism genetic. This research aims at finding the relationship of polymorphism gene of GSTP1 and ABCB1 acting as detoxification enzyme and drug transporter on the incident and severity of myelosuppression induced with cyclophosphamide/doxorubicin.
In this research, we conducted PCR-RFLP examination and sequencing analysis to identify the polymorphism of GSTP1 rs1695(313A>G) and ABCB1 rs1128503(1236C>T) on 79 patients suffered from breast cancer having the therapy with cyclophosphamide, doxorubicin, and fluorouracil. The analysis of relationship with myelosuppression (leukopenia and neutropenia) is then performed postchemotherapy cycle 1 and 3.
The patient found with GSTP1 AG+GG were tend to suffer neutropenia and leukopenia with a severe degree compared to patients with GSTP1 AA (p=0.034, 0R= 5.11, 95% CI = 1,047-24,957) and (p=0, 006 0R=1,8, 95% CI = 1,003-3,229) post chemotherapy cycle 3, and patients with GSTP1 (AG+GG) - ABCB1 (CT+ TT) tend to suffer from neutropenia and leukopenia with a more severe degree than non-GSTP1 (AG+GG) - ABCB1 (CT+ TT) patients (p=0,04, OR=4,899, 95% CI=0,999-23,929) and (p= 0,003, OR = 2.00, 95% CI=1,0002-3,999)
Conclusion:
Our research suggests that polymorphism of GSTP1 and ABCB1 can be assumed as the risk factor of myelosuppression induced with cyclophosphamide/doxorubicin to Indonesian patients.
