title: Association between TERT promoter polymorphisms and acute myeloid leukemia risk and prognosis.
abstract: Telomerase reverse transcriptase gene (TERT) promoter mutations are identified in many malignancies but not in hematological malignancies. Here we analyzed TERT and protection of telomeres 1 gene (POT1) mutations, and four different TERT SNVs in 226 acute myeloid leukemia (AML) patients and 806 healthy individuals in a case referent design, where also overall survival was assessed. A significant association for increased risk of AML was found for TERT SNVs, rs2853669 (OR = 2.45, p = 0.00015) and rs2736100 (OR = 1.5, p = 0.03). The overall survival for patients with CC genotype of rs2853669 was significantly shorter compared to those with TT or TC genotypes (p = 0.036 and 0.029 respectively). The influence of TERT rs2853669 CC on survival was confirmed in multivariable Cox regression analysis as an independent risk biomarker in addition to high risk group, higher age and treatment. No hot spot TERT promoter mutations at -228C > T or -250C > T or POT1 mutations could be identified in this AML cohort. We show that rs2853669 CC may be a risk factor for the development of AML that may also be used as a prognostic marker to identify high risk normal karyotype-AML (NK-AML) patients, for treatment guidance.
authors: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors: Mohamed Ali
authors: MA
authors: Mosrati
authors: Department of Haematology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors: Kerstin
authors: K
authors: Willander
authors: Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors: Ingrid Jakobsen
authors: IJ
authors: Falk
authors: Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors: Monica
authors: M
authors: Hermanson
authors: Division of Hematology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors: Martin
authors: M
authors: Höglund
authors: Section for Hematology and Coagulation, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors: Dick
authors: D
authors: Stockelberg
authors: Section for Hematology and Coagulation, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors: Yuan
authors: Y
authors: Wei
authors: Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.|Department of Hematology, County Council of Östergötland, Linköping, Sweden.
authors: Kourosh
authors: K
authors: Lotfi
authors: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors: Peter
authors: P
authors: Söderkvist
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D053208:Kaplan-Meier Estimate; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D012307:Risk Factors; D019098:Telomerase / Q000235:genetics*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C509186:TERT protein, human; D019098:Telomerase
keywords: AML; SNV; TERT; prognostic markers