Association between the Polymorphism rs3217927 of CCND2 and the Risk of Childhood Acute Lymphoblastic Leukemia in a Chinese Population

Abstract

CyclinD proteins, the ultimate recipients of mitogenic and oncogenic signals, play a crucial role in cell-cycle regulation. CyclinD2, one of the cyclinD family, is overexpressed in T-acute lymphoblastic leukemia (ALL) and B-cell chronic lymphocytic leukemia and involved in the pathogenesis of leukemias. Recent reports indicated that CCND2 polymorphisms are associated with human cancer risk, thusly we hypothesized that CCND2 gene polymorphisms may contribute to childhood ALL susceptibility. We selected the polymorphism rs3217927 located in the 3′UTR region of CCND2 to assess its associations with childhood ALL risk in a case-control study. A significant difference was found in the genotype distributions of rs3217927 polymorphism between cases and controls (P = 0.019) and homozygous GG genotype may be an increased risk factor for childhood ALL (adjusted OR = 1.84, 95% CI = 1.14 —2.99). Furthermore, this increased risk was more pronounced with GG genotype among high-risk ALL (adjusted OR = 1.95, 95% CI = 1.04–3.67), low-risk ALL (adjusted OR = 2.09, 95% CI = 1.13–3.87), B-phenotype ALL patients (adjusted OR = 1.78, 95% CI = 1.08–2.95) and T-phenotype ALL patients (adjusted OR = 2.87, 95% CI = 1.16–7.13). Our results provide evidence that CCND2 polymorphism rs3217927 may be involved in the etiology of childhood ALL, and the GG genotype of rs3217927 may modulate the genetic susceptibility to childhood ALL in the Chinese population. Further functional studies and investigations in larger populations should be conducted to validate our findings.

Interaction Between IGF1 Polymorphisms and the Risk of Acute Lymphoblastic Leukemia in Chinese Children

“…By binding to the IGF1R, it initiates intracellular signal pathway, including PI3K-AKT pathway, a stimulator of cell growth and proliferation, and a potent inhibitor of programmed cell death. Our previous studies have demonstrated that polymorphisms in the PI3K-AKT pathway are associated with risk for childhood ALL [10,11]. There is mounting evidence that IGF1 plays an important role in neoplasia [12,13,14,15].…”

“…Multiple GWAS identified a series of risk loci such as ARID5B, IKZF1, GATA3, CDKN2A, and BMI1-PIP4K2A [6,7,8,9], which have not been consistently identified across these GWAS but validated by meta-analyses. Our previous studies have demonstrated that polymorphisms in the PI3K-AKT pathway are associated with risk for childhood ALL [10,11]. …”

Identification of CD34+ and CD34− leukemia-initiating cells in MLL-rearranged human acute lymphoblastic leukemia

“…CCND2 (cyclin D2) and BAALC expression have prognostic relevance in leukemia and other malignancies. 58,59 In addition, we compared gene expression profiles of 5 MLL-AF4 cases, 4 MLL-AF9 cases, and 3 MLL-ENL cases with those of normal human BM CD34 1 CD38 2 HSCs isolated from 3 healthy donors. We found relative overexpression of cell surface molecules CD9, CD24, CD32, CD127, and CD180b in MLL-AF4 CD34 Figure 5A).…”

Transcription factor and miRNA co-regulatory network reveals shared and specific regulators in the development of B cell and T cell

“…They regulated different target genes in the two processes and also regulated a few shared target genes, such as CCND2, SH3BP5 and HHEX. Multiple studies suggested that abnormal expression of CCND2 involved in the pathogenesis of leukemia 29 30 .…”