© 2017 Wichtg Publishing
TJ
ISSN 0300-8916
Tumori 2017; 00(00): 000-000
ORIGINAL RESEARCH ARTICLE
identfed. Difuse large B-cell lymphoma risk increases among
patents having a family history of NHL, favoring a genetc con-
tributon to disease risk (2). Genetc susceptbility studies (3, 4)
of DLBCL may be employed to characterize at-risk populatons
and understand disease mechanisms.
The telomeres are a region of repeated noncoding DNA
nucleotdes that block the ends of eukaryotc chromosomes.
Their functon is to protect chromosomal DNA from being lost.
They are shortened afer each cycle of replicaton (5, 6). Telom-
erases are an RNA enzyme complex whose functon is to add
DNA sequence repeats (“TTAGGG”) in the telomere regions.
Human telomerase complex is composed of 2 main compo-
nents: human telomerase reverse transcriptase (hTERT), which
is the catalytc component (7), and telomerase RNA compo-
nent (8). The hTERT gene exists on 5p15.33 (9).
MNS16A is a polymorphic tandem repeat minisatellite
that is located in the downstream area of the hTERT gene. It
was found to possess a promoter actvity. The length of the
MNS16A tandem repeats was found to afect its promoter
actvity, referring to a possible role of MNS16A in regulatng
antsense hTERT mRNA expression (10). Wang et al (10) clas-
sifed MNS16A variable number of tandem repeats (VNTR)
alleles as short repeats (S allele), VNTR-243 and VNTR-272,
DOI: 10.5301/tj.5000653
Associaton of MNS16A VNTR and hTERT rs2736098:
G>A polymorphisms with susceptbility to difuse large
B-cell lymphoma
Enas S. Essa
1
, Hagar A. Alagizy
2
1
Department of Clinical Pathology, Faculty of Medicine, Menoufa University, Shebein ElKom, Menoufa - Egypt
2
Department of Clinical Oncology, Faculty of Medicine, Menoufa University, Shebein ElKom, Menoufa - Egypt
Introducton
Difuse large B-cell lymphoma (DLBCL) is the most common
non-Hodgkin lymphoma (NHL), consttutng up to 25%-30% of
NHL cases worldwide (1). Mechanisms of genetc alteraton in
DLBCL include chromosomal translocatons and aberrant so-
matc hypermutaton. Moreover, altered gene expression in
DLBCL, like nonlymphoid tumors, can be caused by copy num-
ber alteratons or somatc point mutatons. With the emer-
gence of genome-wide single nucleotde polymorphism array
and next-generaton sequencing, more lesions seem to be
ABSTRACT
Purpose: Genetc studies of difuse large B-cell lymphoma (DLBCL) may serve to clarify disease pathogenesis and
mark at-risk populatons. Evidence of long telomeres and high telomerase actvity have been demonstrated in
DLBCL. We aimed to examine human telomerase gene (hTERT) MNS16A variable number of tandem repeats and
hTERT rs2736098: G>A polymorphisms in relaton to DLBCL susceptbility.
Methods: In a case control study, 71 patents with DLBCL and 156 controls were genotyped for MNS16A us-
ing polymerase chain reacton and hTERT rs2736098: G>A using polymerase chain reacton restricton fragment
length polymorphism.
Results: In both codominant and recessive models, there was a signifcant diference in the distributon of
MNS16A genotypes between patents with DLBCL and controls (p = 0.047 and p = 0.018, respectvely). In both
models, carriers of S/S genotype were at higher risk to develop DLBCL (odds rato [OR] 2.51, 95% confdence
interval [CI] 1.19-5.29 and OR 2.19, 95% CI 1.15-4.17, respectvely). In the log-additve model, each copy of S
allele signifcantly increased DLBCL risk in an additve form (p = 0.018, OR 1.57, 95% CI 1.08-2.29). The frequency
distributon of MNS16A S alleles was signifcantly higher in patents than controls (p = 0.012). Carriers of S alleles
were at higher risk to develop DLBCL than carriers of L alleles (OR 1.67, 95% CI 1.12-2.49). hTERT rs2736098: G>A
genotype distributon did not difer signifcantly between patents with DLBCL and controls.
Conclusions: MNS16A genetc variatons are associated with DLBCL susceptbility.
Keywords: Difuse large B-cell lymphoma, hTERT rs2736098, MNS16A, Susceptbility
Accepted: May 22, 2017
Published online: September 23, 2017
Corresponding author:
Enas S. Essa
Department of Clinical Pathology
Faculty of Medicine
Menoufa University
Shebein ElKom
+20/32511 Menoufa, Egypt
enas_said_essa@yahoo.com