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The rs61764370 Functional Variant in the KRAS Oncogene is Associated with Chronic Myeloid Leukemia Risk in Women

  • Gutierrez-Malacatt, Humberto (Posgrado en Ciencias Biologicas, Universidad Nacional Autonoma de Mexico) ;
  • Ayala-Sanchez, Manuel (Service of Hematology, Hospital de Especialidades) ;
  • Aquino-Ortega, Xochitl (Service of Hematology, Hospital de Especialidades) ;
  • Dominguez-Rodriguez, Jacqueline (Service of Hematology, Hospital de Especialidades) ;
  • Martinez-Tovar, Adolfo (Department of Hematology, Hospital General de Mexico) ;
  • Olarte-Carrillo, Irma (Department of Hematology, Hospital General de Mexico) ;
  • Martinez-Hernandez, Angelica (Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Genomica, INMEGEN) ;
  • Cecilia, Contreras-Cubas C (Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Genomica, INMEGEN) ;
  • Orozco, Lorena (Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Genomica, INMEGEN) ;
  • Cordova, Emilio J (Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Genomica, INMEGEN)
  • Published : 2016.06.01

Abstract

Background: Chronic myeloid leukemia (CML) is one of the most frequent hematopoietic malignancies in the elderly population; however, knowledge is limited regarding the genetic factors associated with increased risk for CML. Polymorphisms affecting microRNA (miRNA) biogenesis or mRNA:miRNA interactions are important risk factors in the development of different types of cancer. Thus, we carried out a case-control study to test the association with CML susceptibility of gene variants located in the miRNA machinery genes AGO1 (rs636832) and GEMIN4 (rs2740348), as well as in the miRNA binding sites of the genes BRCA1 (rs799917) and KRAS (rs61764370). Materials and Methods: We determined the genotype of 781 Mexican-Mestizo individuals (469 healthy subjects and 312 CML cases) for the four polymorphisms using TaqMan probes to test the association with CML susceptibility. Results: We found a borderline association of the minor homozygote genotype of the KRAS_rs61764370 polymorphism with an increased risk for CML susceptibility (P = 0.06). After gender stratification, this association was significant only for women (odds ratio [OR] = 13.41, P = 0.04). The distribution of the allelic and genotypic frequencies of the four studied SNPs was neither associated with advanced phases of CML nor treatment response. Conclusions: To the best of our knowledge, this study is the first to show a significant association of the KRAS_rs61764370 SNP with CML. To further determine such an association of with CML susceptibility, our results must be replicated in different ethnic groups.

Keywords

CML;polymorphisms;microRNAs;KRAS

Acknowledgement

Supported by : Universidad Nacional Autonoma de Mexico

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