MITOCHONDRIAL DNA 4977 bp DELETION
IN CHRONIC CERVICITIS AND CERVIX CANCERS Kara M, Tatar A, Borekci B, Dagli F, Oztas S *Corresponding Author: Murat Kara M.D., Department of Genetics, School of Medicine, Firat University,
Universite cad. No. 2, 23119 Elazig, Turkey; Tel: +90-424-233-35-55/1938; Fax: +90-424-238-80-96;
E-mail: drmuratkara@hotmail.com page: 25
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DISCUSSION
Mutations in mitochondrial protein genes are
the reason of not only neurodegenerative diseases
but also ophthalmological and hematological diseases
[12]. Studies demonstrating the relationship of
mtDNA mutations with cancer and infections were
conducted in many different patient groups [10,18].
Accumulation of mtDNA mutations is directly related
to ageing and the development of degenerative
diseases. It has been shown that the 4977 bp deletion
accumulated in tissues such as brain, skeletal
and cardiac muscle increases with age [19]. In this
study, we demonstrated the relationship of 4977 bp mtDNA deletions with chronic cervicitis and cervix
cancer.
Liu et al. [20] determined 60.0% mtDNA mutations
in malignant ovarian tissues. The rate of mtDNA
mutations were 68.8 and 25.0%, respectively,
for malignant tumors and benign tumors. Wu et al.
[17] in their study on 31 gastric cancer patients,
found the 4977 bp deletion in normal gastric tissues
in 17 (55.0%) of 31 patients. They also found that
only three (10.0%) of all gastric cancer samples carried
mtDNA deletions. These fi ndings suggest that
the 4977 bp deletions accumulated in less frequency
in gastric cancer tissues [17].
Cervical cancer is the second most common
cause of cancer deaths after breast cancer in women
and it comprises 10.0% of all cancer deaths [21].
There are few studies investigating the relationship
between mtDNA mutations and cervix cancer
[2,22]. In our study, 9.5% heteroplasmic and homoplasmic
mtDNA 4977 bp deletions were observed in
cervix cancer. In addition, the ages of two patients
with mtDNA 4977 bp homoplasmic deletion were
73 and 79 years. These older ages suggest that the
age-dependent accumulation of mtDNA deletions
is one of the reasons of the frequent homoplasmy
in cervical cancer. Secondly, these patients might
be exposed to more infections because of their advanced
age, and mitochondrial ROS production
might be increased. Thus, chronic infl ammation via
ROS production may lead to mtDNA mutations and
accumulation of mutant mtDNA in cell.
The reason for the lack of deletions in other patients
might be that cells undergo apoptosis when
mitochondrial mutations exceed threshold value
[17]. The evidence suggests that the effects of ROS
on the pathogenesis of chronic diseases including
cancer vary [23]. Although cells have antioxidant
systems against ROS-dependent oxidative damage,
oxidative damages accumulate during life and
this accumulation leads to damage in DNA, proteins
and lipids. Therefore, it is suggested that oxidative
stress has an important role in the development of
age-dependent diseases such as neurodegenerative
disorders, arthritis, arteriosclerosis and cancer [24].
A study by Canakci et al. [25] found that 24 (80.0%)
of 30 chronic periodontitis patients had the 4881 bp
mtDNA deletion. They suggested that increased ROS
production due to infection in chronic periodontitis
may be related to 4881 bp mtDNA deletion [25].
In our study, patients with chronic cervicitis had
a higher frequent heteroplasmic mtDNA 4977 bp
deletions. This fi nding supports the hypothesis that
increased ROS production during chronic infl ammation
in cervix tissues leads to mtDNA mutations.
However, the minimum threshold effect should be
exceeded by the emergence of clinical fi ndings and
dysfunction in tissues [6,26]. This idea may show
that mutation rate is important in disease expression
and in defi ning mitochondrial diseases.
This is the fi rst study that uses the mtDNA
4977 bp deletion in understanding of pathogenesis
in patients with chronic cervicitis and cervix
cancer. Investigating other mtDNA mutations in
these patient groups may gain insight for clinical
approaches.
Declaration of Interest. The authors report no
confl icts of interest. The authors alone are responsible
for the content and writing of this article.
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