Role of the functional MNS16A VNTR‐243 variant of the human telomerase reverse transcriptase gene in progression and response to therapy of patients with non‐Hodgkin's B‐cell lymphomas

Abstract

MNS16A is a functional polymorphic tandem repeat within the human telomerase reverse transcriptase (hTERT) gene. To investigate whether any of the MNS16A repeats represents a genetic risk factor for NHL susceptibility, progression of or response to therapy in 75 patients with non-Hodgkin's lymphomas (NHLs) and 126 healthy individuals were genotyped using the PCR-VNTR technique. A slightly higher frequency of the MNS16A VNTR-243 variant was detected among patients who did not respond to treatment (NR) as compared to patients with complete or partial remission (0.83 vs. 0.51, P = 0.055). NR patients more frequently developed aggressive than indolent type of the disease (0.92 vs. 0.41, P = 0.001). The VNTR-243 allele was more frequently detected among patients with an intermediate-high/high International Prognostic Index (IPI 3-4) score (P = 0.063), especially in patients with advanced age and IPI 3-4 (P = 0.040). In multivariate analysis, higher IPI 3-4 score (OR = 11.364, P = 0.051) and aggressive type of the disease (OR = 18.182, P = 0.012) were found to be independent genetic markers associated with nonresponse to treatment. Presence of the MNS16A VNTR-243 variant also strongly tended to affect the risk of a less favourable response to therapy and was more frequently present among nonresponders (OR = 5.848, P = 0.059). Genetic variation within the hTERT gene may affect the progression and treatment of lymphoproliferative disorders.

Association of MNS16A VNTR and hTERT rs2736098: G>A polymorphisms with susceptibility to diffuse large B-cell lymphoma

“…These results are in disagreement with the study on European populations by Wysoczanska et al (22), who reported that MNS16A genotypes and allele frequencies did not show association with predisposition to B-NHL. Ethnicity differences in the study population should be considered, as polymorphisms vary with ethnicity and geographic distribution of the observation group.…”

“…Ethnicity differences in the study population should be considered, as polymorphisms vary with ethnicity and geographic distribution of the observation group. Furthermore, Wysoczanska et al (22) investigated a heterogeneous sample of B-NHLs that included 26 patients with DLBCL. Wang et al (10) proposed that MNS16A has hTERT repressor promoter activity that is significantly lower in the construct containing the shorter repeats.…”

TERT—Regulation and Roles in Cancer Formation

“…As a result, the S allele is associated with higher telomerase activity, while LL homozygotes have lower telomerase activity ( 158 ). Our previous work showed that the S variant was more frequent in non-Hodgkin’s B-cell lymphoma patients how did not respond to treatment, as well as those with intermediate/high International Prognostic Index ( 159 ). In contrast, the S variant was less frequent in chronic lymphocytic leukemia patients with high disease stage ( 160 ).…”

Telomerase Activation in Hematological Malignancies

“…The rs2735940 T allele increased the levels of the TERT mRNA compared with the C allele [ 84 ]. The role of the mechanism of hTERT regulation was also demonstrated via MNS16A polymorphism in patients with Non-Hodgkin Lymphoma (NHL) [ 85 ]. The polymorphic element MNS16A, located downstream of exon 16 of the TERT gene and upstream of the putative promoter region of an antisense TERT transcript, has promoter activity depending on the number of tandem repeats.…”