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

Int J Immunogenet. 2015 Apr;42(2):100-5. doi: 10.1111/iji.12182. Epub 2015 Feb 12.

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Case-Control Studies
  • Disease Progression
  • Female
  • Genetic Association Studies*
  • Genotype
  • Humans
  • Lymphoma, B-Cell / genetics*
  • Lymphoma, B-Cell / mortality
  • Lymphoma, B-Cell / pathology
  • Lymphoma, B-Cell / therapy
  • Male
  • Middle Aged
  • Minisatellite Repeats / genetics*
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • Telomerase / genetics*
  • Treatment Outcome
  • Young Adult

Substances

  • TERT protein, human
  • Telomerase