Leukocyte Telomere Length Shortening, hTERT Genetic Polymorphisms and Risk of Childhood Acute Lymphoblastic Leukemia

Background: Telomeres are involved in chromosomal stability, cellular immortality and tumorigenesis. Human telomerase reverse transcriptase (TERT) is essential for the maintenance of telomere DNA length. Recently, a variable tandem-repeats polymorphism, MNS16A, located in the downstream region of the TERT gene, was reported to have an effect on TERT expression and telomerase activity. Previous studies have linked both relative telomere length (RTL) and TERT variants with cancer. Therefore, we evaluated associations between RTL, TERT gene polymorphisms (hTERT, rs2735940 C/T and MNS16A Ins/Del) and risk of childhood acute lymphoblastic leukemia (ALL) in an Iranian population. Methods: RTL was determined by a multiplex quantitative PCR-based method, and variants of the hTERT, rs2735940 C/T and MNS16A Ins/Del, were genotyped by amplification refractory mutation system PCR (ARMS-PCR), and PCR, respectively. Results: Our results indicated that RTL was shorter in ALL patients (1.53±0.12) compared to the control group (2.04±0.19) (P=0.029). However, no associations between hTERT gene variants or haplotypes and the risk of childhood ALL were observed (P>0.05). Also hTERT polymorphisms were not associated with RTL or patient clinicopathological characteristics, including age (P=0.304), sex (P=0.061) organomegally (P=0.212) CSF involvement (P=0.966) or response to treatment (P=0.58). Conclusions: We found that telomere attrition may be related to the pathogenesis of childhood ALL, irrespective to TERT variants.