dc.description.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 | en_US |