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Chronic  myeloid leukemia is a hematopoietic stem cell disorder that causes uncontrolled  proliferation of white blood cells. Although the clinical and biological  aspects are well documented, little is known about individual susceptibility to  this disease. We conducted a case-control study analyzing the prevalence of the  polymorphisms MTHFR C677T, MTHFR A1298C, del{GSTM1}, del{GSTT1},  and haptoglobin in 105 patients with chronic myeloid leukemia (CML) and 273  healthy controls, using PCR-based methods. A significant association with risk  of developing CML was found for MTHFR 1298AA (odds ratio (OR) = 1.794;  95% confidence interval (CI) = 1.14-2.83) and GSTM1 non-null (OR =  1.649; 95%CI = 1.05-2.6) genotypes, while MTHFR 1298AC (OR = 0.630;  95%CI = 0.40-0.99) and GSTM1 null (OR = 0.606; 95%CI = 0.21-0.77)  genotypes significantly decreased this risk. There appeared to be selection for  heterozygosity at the MTHFR 1298 locus. The considerable range of  variation in this and other human populations may be a consequence of  distinctive processes of natural selection and adaptation to variable  environmental conditions. The Brazilian population is very mixed and  heterogeneous; we found these two loci to be associated with CML in this  population.

genetics and molecular research

Association between methylene tetrahydrofolate reductase and glutathione S-transferase M1 gene polymorphisms and chronic myeloid leukemia in a Brazilian population