Genetic variants in the candidate genes of the apoptosis pathway and susceptibility to chronic myeloid leukemia.
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder, characterized by the presence of BCR/ABL fusion gene. It is unclear which cellular events drive BCR/ABL gene translocation or initiate leukemogenesis in CML. Bcl-2 promotes survival of hematopoietic stem cells. Accordingly, apoptosis-related pathway may involve in the leukemogenesis of CML. In the current study, we evaluated 80 single nucleotide polymorphism (SNP) markers involved in the pathways of apoptosis (n = 30), angiogenesis (n = 7), myeloid cell growth (n = 14), xenobiotic metabolism (n = 13), WT1 signaling (n = 7), interferon signaling (n = 4), and others (n = 5) in 170 CML patients and 182 healthy controls. In a single-marker analysis, the following SNPs were identified including VEGFA, BCL2, CASP7, JAK3, CSF3, and HOCT1. In the multivariate logistic model with these SNPs and covariates, only BCL2 (rs1801018) was significantly associated with the susceptibility to CML (P = .05; odds ratio [OR] 2.16 [1.00-4.68]). In haplotype analyses, haplotype block of BCL2 consistently showed significant association with the susceptibility to CML. Risk allele analysis showed that a greater number of risk alleles from BCL2 SNP correlated to increasing risk of CML (overall P = .1, OR 1.84 [1.06-3.22] for 3-4 risk alleles vs 0-1 risk alleles). The current study indicated that BCL2 SNP seemed to be associated with increasing susceptibility to CML.
Kim
Dong Hwan Dennis
DH
Chronic Myelogenous Leukemia Group, Department of Hematology/Medical Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, ON, Canada. drkiim@medimail.co.kr
Xu
Wei
W
Ma
Clement
C
Liu
Xiangdong
X
Siminovitch
Katherine
K
Messner
Hans A
HA
Lipton
Jeffrey H
JH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D018816:Genes, cdc; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D038042:Myelopoiesis / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction / Q000235:genetics; D055815:Young Adult