title: The rs61764370 Functional Variant in the KRAS Oncogene is Associated with Chronic Myeloid Leukemia Risk in Women.
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).
  
  
  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.
authors.affiliation: Posgrado en Ciencias Biologicas, Universidad Nacional Autonoma de Mexico, SS, Mexico, D.F. Mexico E-mail : ecordova@inmegen.gob.mx.
authors.forename: Humberto
authors.initials: H
authors.lastname: Gutiérrez-Malacatt
authors.forename: Manuel
authors.initials: M
authors.lastname: Ayala-Sanchez
authors.forename: Xochitl
authors.initials: X
authors.lastname: Aquino-Ortega
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Dominguez-Rodriguez
authors.forename: Adolfo
authors.initials: A
authors.lastname: Martinez-Tovar
authors.forename: Irma
authors.initials: I
authors.lastname: Olarte-Carrillo
authors.forename: Angelica
authors.initials: A
authors.lastname: Martinez-Hernandez
authors.forename: Cecilia Contreras-Cubas
authors.initials: CC
authors.lastname: C
authors.forename: Lorena
authors.initials: L
authors.lastname: Orozco
authors.forename: Emilio J
authors.initials: EJ
authors.lastname: Cordova
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D035683:MicroRNAs; D016283:Proto-Oncogene Proteins p21(ras)