title: Frequency and prognostic significant of CYP3A4-A-290G polymorphism in acute myeloid leukemia.
abstract: Cytochrome P450 3A4 (CYP3A4) is the most plentiful cytochrome P450 in adult human liver and small intestine and is responsible for detoxification of more than 50% of drugs in addition to the metabolic deactivation and metabolism of many carcinogens. Polymorphism of CYP3A4-A-290G considered the only allele that appears to stimulate CYP3A4 expression and has been associated with a number of clinical phenotypes, including prostate cancer, breast cancer, leukemia and the early onset of puberty. In this study, we analyzed the presence of CYP3A4-A-290G polymorphism in 77 newly diagnosed AML cases and 72 healthy control using PCR/RFLP aiming to show CYP3A4-A-290G polymorphism pattern in acute myeloid leukemia patients, and its role in disease severity and progression. A highly statistically significant difference was found between the control and AML groups as regards the heterozygous genotype (p-value = 0.002) and increases the risk of AML 11.4-fold. Also there was a highly significant difference between the control and AML patients regarding variant allele (G in AG and GG genotypes) (p-value 0.001) and increases the risk of AML 19-fold. No statistically significant association found between the CYP3A4-A-290G polymorphism and different clinical or laboratory parameters as well as an initial response to treatment, overall survival and the disease free survival. We concluded that CYP3A4-A-290G polymorphism is a genotypic factor that increases the CYP3A4 enzymatic activity and increases the risk of AML by 18.9-fold.
authors: Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
authors: Gamal T
authors: GT
authors: Ali
authors: Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
authors: Nevin M
authors: NM
authors: Al-Azhary
authors: Clinical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors: Doha A
authors: DA
authors: Mokhtar
keywords: 290G; AML; CYP3A4-A; PCR/RFLP; Prognosis