Hubungan Polimorfisme Glutathion S­ Transferase P-1 (GSTPl) dengan Insidensi dan Derajat Mielosupresi pada Pasien Kanker Payudara yang Diterapi dengan Regimen Mengandung Siklofosfamid

Abstract

As one of most important breast cancer treatments, chemotherapy often complicated by hematopoetic toxicity. Today, Genetic polymorphism has been linked to inter individual differences in terms of toxic severity of various cytotoxic agent Glutathion S-Transferase (GSTs) enzymes detoxifies the chemotherapy drugs and their metabolites. However,AG polymorphism at nucleotide 313in exon 5 of GSTP1 gene leads toan amino acid substitution of isoleusin (Ile) by Valin (Val) at 105 amino acid position (Ile105Val). This substitution result in diminishing the enzymatic activity of Valine amino acid which lead to a reduction of detoxification ability, Hence, the aim of this study was to investigate the association between GSTP1 313AG polymorphism and the incidence and severity of myelosuppression in breast cancer patient treated with CAFICEF regimen.

91 Indonesian breast cancer patients of Haji Adam Malik Hospital who had been diagnosed and treated with Cyclophospamide, Doxorubicin/Epirubicin, 5-FU regimen (CAF/CEF) were selected for this cohort retrospective study. DNA was extracted from pheripheral leucocytes and the status of GSTP1 313 AG polymorphism was determined using Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) method. The incidence and grades myelosupression (anemia, leucopenia,neutropenia and thrombocytopenia) were collected from patient's medical record. The association of GSTP1 genotypes on the differences and grades myelosupression post-chemotherapy in the first and third cycle was assessed using ChiSquare. Logistic regression analysisi was used to assess the influence of GSTP1 Polymorphism and other covariat on the incidence of myelosupression. The proportion of A313A,A313G,G313G genotype GSTP1 are 60,4%,, 29,7% and 9,9% respectively. There was no association between the incidence of myelosupression from post chemotherapy in the first and third cycle in G313G GSTPI polymorphism (p>0.05). GSTP1 mutant (A313G GSTP1 and GSTPI) were associated significantly with leucopenia severity post chemotherapy of the third cycle as compared with GSTP1 A3134 genotype (wildtype) (p<0,05)). No association was found between the incidence of myelosupression with the age of patients, tumor staging liver function, renal function and nutrition state. In conclusion, This study showed that GSTP1 polymorphism was not associated with incidence of myelosupression in breast cancer patients receiving cyclophosphamide-contained chemaotherapeutic regimen, however, it associated with the severity of grade myelosuppression.