Page 82 - GTM-2-1

Global Translational Medicine Telomere length, mtDNA copy number and colorectal cancer

Cancer primarily represents an age-related group of 2. Methods
pathologies and is among the top 20 causes of death .
[2]
Colorectal cancer (CRC) is the third most common type of 2.1. Study participants
cancer in men and the second in women worldwide, with a A random population sample of men and women aged
mortality rate of 11.0 and 7.2/100,000, respectively . 45 – 69 years old was examined at baseline in 2003/05
[3]
(n = 9360, mainly Caucasoid) and re-examined in 2006/08
Environmental factors contribute significantly to the
risk of CRC development; however, there are also non- and 2015/18 in Novosibirsk (Russia) in the frame of the
HAPIEE study (Health, Alcohol and Psychosocial Factors
modifiable risk factors, such as older age, family history of in Eastern Europe; http://www.ucl.ac.uk/easteurope/
cancer , and molecular genetic contributors .
[4]
[5]
hapiee-cohort.htm). The baseline cohort was followed-up
Considering the multifaceted process of aging for cancer, CVD, and all-cause mortality until December
accompanied by health decline, the molecular markers 31, 2019, for an average of 15.6 years (standard deviation,
of “biological age” may reflect the signals of the pace of SD 0.70; median 15.6; range 14.5 – 17.0), calculated across
aging. Among the potential markers of biological age, those alive until censoring date.
telomere length and mitochondrial DNA copy number In the present analysis, we focused on the most common
(mtDNA-CN) have been extensively studied. Telomeres are cancer: CRC. Data on CRC (ICD-10: C18 – C20) in the
nucleoprotein complexes that are located at chromosome cohort were collected, including fatal and non-fatal events.
ends and support chromosomal stability by protecting For cancer events ascertainment, we used the Cancer
against DNA degradation . Shortened telomeres Register of Novosibirsk city. In addition, the following
[6]
eventually lead to cellular senescence, and telomere length sources were used to collect information on all-cause
is regarded as a likely biomarker of a history of replication and cause-specific mortality: The Bureau of Population
and cumulative oxidative stress . When telomeres Registration (ZAGS), the State Statistical Bureau of the
[6]
become critically short, the life cycle of cells stops . Novosibirsk Region, and the data obtained from additional
[7]
A shorter leukocyte telomere length (LTL) has been sources at two re-examinations of the cohort (including
found to be associated with age [8,9] , male sex , age-related the address bureau and proxy-information on deceased
[10]
risk factors for cardiovascular disease (CVD) and non- respondents of the study).
communicable disease [11,12] , and all-cause mortality [9,13-15] .
These associations are independent of chronological age, 2.2. Ethical approval and consent
which points at an extra value of telomere length as a sign The study was conducted in accordance with the guidelines
of cellular or biological aging. of the Declaration of Helsinki. The ethical approval for the
In multiple cellular processes such as lipid study was from the Ethics Committee of IIPM – Branch
metabolism, apoptosis, and cell differentiation, of IC&G SB RAS (Institute of Internal and Preventive
mitochondria are engaged in energy production Medicine – Branch of Federal State Budgeted Research
(oxidative phosphorylation) and also participate in the Institution, “Federal Research Center, Institute of Cytology
generation of reactive oxygen species (ROS), which is and Genetics, Siberian Branch of the Russian Academy of
the crux of the free-radical theory of aging [16] . According Sciences”) (protocol #1, March 14, 2002, and protocol #12,
to experimental results, ROS could act as “mediators” of December 8, 2020). All the study participants signed an
the stress response to the damage induced by aging [17] . informed consent.
MtDNA-CN is a marker of mitochondrial replication 2.3. Sample selection
and cellular energy reserve [18] . Although mtDNA-CN is
an indirect indicator of mtDNA damage, it is associated Among 9360 people, 160 events of CRC were ascertained
with mitochondrial enzyme activity and adenosine during a 15-year follow-up period, including repeated
triphosphate production [19] . events in several participants. The present study was
designed as a nested case-control. We selected incident
The evaluation of the possible association between LTL
and the risk of cancer [14,20-23] and that between alternations CRC cases among those free from baseline cancer of any
site and with available DNA samples (n = 154) for analysis.
in mtDNA-CN and cancer [24-27] has shown inconsistent The universal control group for the present study was
findings. formed based on certain criteria; we excluded those with
We aimed to study the association of LTL and baseline cancer or CVD, or those who died within the
mtDNA-CN with the risk of incident CRC during a 15-year follow-up period. These exclusion criteria were applied to
follow-up period. generate universal controls suitable for several outcomes.

Volume 2 Issue 1 (2023) 2 https://doi.org/10.36922/gtm.v2i1.184