The risk and prognostic influence of caspase 9 promotor polymorphisms in Egyptian patients with acute myeloid leukemia

Abstract

Acute myeloid leukemia (AML) is a genetic disorder of hematopoietic stem cells (HSCs) followed by clonal selection and uncontrolled proliferation leading to malignant neoplasm. Inappropriate regulation of apoptosis contributes to many human disorders including cancer. Caspase 9 (CASP9) is associated with the intrinsic pathway of apoptosis. Functional single-nucleotide polymorphisms (SNPs) in CASP9 might influence gene expression leading to altered apoptosis and increased AML risk. Previously, two CASP9 promoter polymorphisms (CASP9 1263 rs4645978A > G and CASP9 712 rs4645981C > T) were shown to be associated with increased risk of developing AML and inferior AML survival in South Indian subjects. This study was to evaluate these polymorphisms in an independent cohort of AML patients and controls in Egypt. PCR–RFLP for CASP9 1263 rs4645978 A > G and CASP9 712 rs4645981 C > T genotypes were done in 60 de novo AML cases and 40 healthy control subjects. Our study showed that CASP9 712 rs4645981 C > T gene polymorphism is associated with increased risk of developing AML and poor disease outcome (p value = 0.006, < 0.001; OR = 3.644, 26; and 95% CI = 1.39–9.528, 6.5–103.5, respectively). In contrast, CASP9 1263 rs4645978 A > G showed no significant difference between AML patients and the controls regarding the risk of developing AML or disease outcome (p value = 0.301, 0.573, respectively). CASP9 712 rs4645981 C > T could be involved in the pathophysiology and development of AML in Egypt and may be useful as a predictive molecular markers for inferior prognosis in AML. Notably, risk was highest and outcomes worst in patients with both the 712C > T and 1263A > G alleles.