The influence of glutathion S-transferase P-1 polymorphism A313G rs1695 on the susceptibility to cyclophosphamide hematologic toxicity in Indonesian patients
Abstract: Chemotherapy often
causes side effects such as hematologic toxicity. The degree of toxicity is
often associated with genetic polymorphism. This study aims to determine the
influence of GSTP1 A313G polymorphism, an enzyme responsible for detoxifying
cyclophosphamid, on incidence and severity of cyclophosphamid hematologic
toxicity.
Methods: 91 Indonesian females diagnosed with breast cancer at Haji Adam
Malik Central General Hospital, Medan, receiving cyclophosphamide,
doxorubicin/epirubicin and 5-FU were included in this retrospective cohort
study. DNA was extracted from peripheral leukocytes and GSTP1 A313G genotyping
was analyzed using polymerase chain reaction-restriction length fragment
polymorphism (PCR-RFLP). Genotype deviation and allele frequencies were also
determined by Hardy-Weinberg Equilibrium. The degrees of hematologic toxicity
(leucopenia and neutropenia data after chemotherapy cycles 1 and 3) were
collected from the patient medical records. The data were analyzed using
chi-square test.
Results: 60.4% of the patients had the wildtype (A/A), while 29.7% were
heterozygous (A/G), and 9.9% were homozygous mutant (G/G). There was no
significant deviation of allele and genotype frequency from Hardy-Weinberg
Equilibrium. The G allele (A/G & G/G) contributes to more severe degree of
leukopenia compared to patients with wild type allele (A/A) (p<0.05) after the 3rd chemotherapy
cycles.
Conclusion: There was association between GSTP1 polymorphism with the
degree of hematologic toxicity in breast cancer patients receiving
cyclophosphamide chemotherapy regimen.
Author: Dita Hasni, Kamal B.
Siregar, Hadyanto Lim
Journal Code: jpkedokterangg160142