Can Polymorphisms In Oxidative Stress Related Genes Be a Risk Factor For CML?

Oxidative stress (OS) is recognized to be a evident feature in cancer development and progression. Indirect evidences suggest a role for oxidative stress (OS) in Chronic Myelogenous Leukemia (CML) etiology and pathogenesis. OS, resulting from an imbalance between Reactive Oxygen Species (ROS) production and antioxidant defenses, contributes to cell damage, apoptosis and ineffective hematopoiesis. The antioxidant enzymes superoxide dismutases (SOD) and catalase (CAT) are important components of cell defense against OS, and polymorphisms in the genes may contribute to differences in susceptibility of individuals to oxidative damage since it can lead to reduced protection against OS.

In the present study we set to investigate the influence of polymorphisms of oxidative stress related genes, namely SOD1 (A251G), SOD2 (Ala16Val), COX2 (G-765C), CAT (C-262T) and NADPH oxidase p22 phox (C242T), as a risk factor for CML development and also as a prognostic risk marker in CML patients.

Our study population consisted of 48 patients diagnosed with CML and the same number of healthy controls. Diagnosis was set according to international criteria. The genetic polymorphisms of SOD1 (A251G), SOD2 (Ala16Val), COX2 (G-765C), CAT (C-262T) and NADPH oxidase p22 phox (C242T) were assessed by RFLP-PCR. The patient group median age was 51 years (18-86), gender M/F=27/21. The strength of association between polymorphisms and CML risk was assessed by odds ratio (OR) with the corresponding 95% confidence interval (CI95%) and Kaplan-Meier survival analysis will be assessed to investigate the prognostic importance of these polymorphisms.

Our preliminary results show a higher wild type allelic frequency of SOD1 (94%), COX2 (80%), CAT (82%) and NADPH oxidase p22 phox (67%) polymorphism and a higher variant allelic frequency SOD2 (52%) in CML patients, compared to controls. In these patients the predominant genotype was AA (88%), CG (52%), GG (67%), CC (73%) and CT (46%), respectively for SOD1, SOD2, COX2, CAT and NADPH oxidase p22 phox. Besides that, individuals with CC genotype of NADPH oxidase p22 phox and with TT genotype of CAT have an increase risk for CML about 2,3636-fold (CI95% 1,0346-5,3997; p=0,032) and 12,368-fold (CI95% 1,5151-100,9687; p=0,0076), respectively.

These preliminary results show that CAT (C-262T) and NADPH oxidase p22 phox (C242T) genetic polymorphisms might be related with CML development and may be a novel genetic markers for CML susceptibility.