title: Investigation and analysis of single nucleotide polymorphisms in Janus kinase/signal transducer and activator of transcription genes with leukemia.
abstract: Aberrant activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway may predispose to leukemia due to deregulation of proliferation, differentiation or apoptosis. This study was conducted to investigate whether any association exists between genetic polymorphisms in the JAK2, STAT3 and STAT5 genes and individual susceptibility to leukemia. A case-control study was carried out using a Chinese sample set with 344 cases of leukemia and 346 controls matched by age and ethnicity. Genomic DNA was assayed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) on 13 single nucleotide polymorphisms (SNPs). Genotype analyses showed that two SNPs, namely rs17886724 and rs2293157 located in STAT3 and STAT5, respectively, were significantly associated with leukemia (p < 0.05 for all). Interaction analyses of SNPs (rs17886724|rs2293157; rs11079041| rs2293157) showed that there were inferior associations in chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) compared to the control group (0.1 > p > 0.05). Linkage disequilibrium existed between rs11079041 and rs2293157 in both leukemia and control groups (r(2) = 0.7). The haplotypes displayed significant association between rs11079041 and rs2293157 in both leukemia and control groups (p < 0.05). The accuracy rate of the support vector machine (SVM) classification model in making a prediction of leukemia was 97%. The results indicated that STAT3 and STAT5 gene SNPs may be prognostic of leukemia.
authors: Jiangsu Institute of Cancer Research, Nanjing, China.
authors: Yuejiao
authors: Y
authors: Zhong
authors: Jianzhong
authors: J
authors: Wu
authors: Baoan
authors: B
authors: Chen
authors: Rong
authors: R
authors: Ma
authors: Haixia
authors: H
authors: Cao
authors: Zhuo
authors: Z
authors: Wang
authors: Lu
authors: L
authors: Cheng
authors: Jiahua
authors: J
authors: Ding
authors: Jifeng
authors: J
authors: Feng
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053614:Janus Kinase 2 / Q000032:analysis / Q000235:genetics; D053612:Janus Kinases / Q000032:analysis / Q000235:genetics*; D007938:Leukemia / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D050791:STAT Transcription Factors / Q000032:analysis / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000032:analysis / Q000235:genetics; D050799:STAT5 Transcription Factor / Q000032:analysis / Q000235:genetics; D055815:Young Adult
chemical_list: D050791:STAT Transcription Factors; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D053612:Janus Kinases