The Effect of FOXO3a rs4946936 Gene Polymorphism on Imatinib Mesylate Therapy Response in Javanese Race CML patients at Dr. Saiful Anwar General Hospital Malang

Abstract

Genetic factors are known to play a role in the therapeutic response of several diseases, especially malignancy. In the process of apoptosis, Forkhead O transcription factor sub family 3a (Foxo3a) is involved in mitochondria-related and unrelated processes by triggering the expression of death receptor ligands such as Fas ligands, TNF apoptotic ligands and Bcl-xL, bNIP3, Bim from members of the Bcl2 family. In a study using a cell line, Foxo3a inactivation was shown due to a mutation in the FOXO3a gene, and this inactivation was associated with cancer progression. In addition, failure to induce apoptosis so that cancer cells continue to survive and spread is also the cause of failure to achieve a treatment response. This study aims to determine the role of genetic factors in the form of the FOXO3a rs4946936 gene polymorphism in response to imatinib mesylate therapy. This prospective cohort study was conducted at dr. Saiful Anwar General Hospital between February 2019 and February 2021. The method used for sampling was consecutive sampling. This study was approved by the ethic department of dr. Saiful Anwar General Hospital. Regression test were used to observe the effect of the FOXO3a rs 4946936 gene on the therapeutic response. Our results showed that the CC genotype was more common in the treatment response group, while the TT genotype was more common in the non-treated group. The TC genotype FOXO3a rs4946936 had a 6.96 (p=0.004) times risk of not achieving a major molecular response compared to the CC genotype. The TT genotype had a 17 times risk (p=0.003) of not achieving a major molecular response than the CC genotype. FOXO3a rs4946938 gene polymorphism influenced the response to imatinib mesylate therapy in CML patients. The CC genotype was more likely to achieve a therapeutic response than other genotypes and the T-allele was a susceptibility allele not to achieve a major molecular response.