Hubungan Polimorfisme Glutathion S- Transferase P-1 (GSTP1) dengan Insidensi dan Derajat Mielosupresi pada Pasien Kanker Payudara yang Diterapi dengan Regimen Mengandung Siklofosfamid

Abstract

As one of mast intportant breast c(mcer treatments, chemotherapy ofien complicated by hematopoettc toxictty. Toduy, Genetic polymorphism has been linlred to inter individual dffirences in terms af toric severtty of various cytotoxic ogent. Glutathion S-Traruferase (GSTs) en4ntes detoxifies the chemotherayy drugs otrd their metabolites. However,AlG polymorphism at mtcleotide 313in exon 5 of GSTPI gene leads taan amino ocid substitution of isoleusin Qle) by Volin (VaI) dt 105 amina acid position (Itel05Val).This substitution result in diminishing the enrymatic activityof Yaline amino acidwhich lead to a reduction of daoxtfication ability, Hence, the aim of this study wos to invesfigate the associatio,n between GSTPI 3l3AGpolynorphism and the ircidence and severity of myerysuppression in breast cancir patient treatedwith CAFiCEF regimen. Sl9I Indonesian breast cancer patients of Haii Adam Malik Hospttal who had been diagnosed and treated with Cycloplnspantide,DoxarubicidEpirubicia 5-FU regimen (CAF/CEF) were selectedfor this cohort retrospecttve stady. DNA was extracted from pheripheral leucoqttes and the status of GSTPI i13 AG polymorphism was determined using Polynerase Chain Reaetion Restriction Fragment Length Polynorphism (PCR-fuFLP) method. The incidence and grades myelosupression (anemia,leucopenta,neutropenia and thrombocytopenia) were collected from patient's medical record. Tlw association of GSTPI gerntypes on the dffirences and grades myelosupression post-chemotherapy in the first and third cycle was dssessed using Chisquare. Logistic regression analysisi was used to assess the influence of GSTPI Polymorphism and other coyariat on the

incidence of nryelosupr ession- The proportion of A3|3A,A3L3G,G?I3G gerntype GSTPI are 60,40/o,,

29,795 and 9,9 96 respectively. There wos no association between the incidence of myelosupression from post chemotlwrapy in the first and third cycle in G3l3G GSTPI polymorphism (p:0,372 vs 0,930). GSTPI mutant (A313G GSTPT and GSTPI) were associatedsignificantly wtth leucopenia severity post chemotherapy of the third q,cle qs cot"4wred wtth GSTPI A3l jA genofi,pe (wildtype) (p:0,008). No associatton wos found between the incidence af myelosupresstan with the age of patienls, tumor stagingliverfunction, renalfunction and nutrition state. In concluston, Ihis study showed that GSTPI polymorphism was not associoted with incidence of myelosupression in breast cancer patients receiving cyclophosphamide-contoined chemaotherapeutic regimen,however,it was

associatedwith the severity of grade myelosuppression