Page 81 - GTM-2-1

Global Translational Medicine

ORIGINAL RESEARCH ARTICLE
Leukocyte telomere length and mitochondrial

DNA copy number association with colorectal
cancer risk in an aging population

Sofia Malyutina *, Vladimir Maximov , Olga Chervova , Pavel Orlov , Vitaly
1
1
2
1
Voloshin , Andrew Ryabikov , Mikhail Voevoda , and Tatiana Nikitenko 1
1
1
3
1 Research Institute of Internal and Preventive Medicine - Branch of Institute of Cytology and Genetics
SB RAS, Novosibirsk 630089, Russia
2 UCL Cancer Institute, University College London, London WC1E6BT, UK
3 Royal Botanical Gardens Kew, London TW9 3AE, UK
Abstract

In this study, we evaluated the association of blood leukocyte telomere length (LTL)
and mitochondrial DNA copy number (mtDNA-CN) with the risk of incident colorectal
cancer (CRC). We studied and followed-up a cohort of Russian men and women
(aged 45 – 69 years, n = 9360, 54% female) from the HAPIEE study for 15 years. Using
the nested case-control design, we selected cases with incident CRC among those
free from any baseline cancer (n = 146) and sex- and age-stratified controls among
those free from baseline cancer and cardiovascular disease and alive at the end of
the follow-up (n = 799). We employed multivariable-adjusted logistic regression to
estimate the odds ratios (ORs) of CRC per 1 decile of LTL or mtDNA-CN. We observed
*Corresponding author: an inverse association of LTL and mtDNA-CN baseline values with the 15-year risk of
Sofia Malyutina incident CRC. Carriers of shorter telomeres had an increased 15-year risk of incident
(smalyutina@hotmail.com)
CRC with adjusted OR 3.2 (95% CI: 2.56 – 3.87, P < 0.001) per 1 decile decrease in LTL,
Citation: Malyutina S, Maximov V, independent of baseline age, sex, smoking, body mass index, blood pressure, lipid
Chervova O, et al., 2023, Leukocyte
telomere length and mitochondrial levels, and education. Similarly, lower mtDNA-CN was associated with the higher risk of
DNA copy number association with incident CRC with adjusted OR 1.7 (95% CI: 1.12 – 1.89, P < 0.001) per 1 decile decrease
colorectal cancer risk in an aging in mtDNA-CN, independent of the aforementioned factors. Using the modified values
population. Global Transl Med,
2(1): 184. of LTL and mtDNA-CN adjusted for multiple factors and their interactions with a case–
https://doi.org/10.36922/gtm.v2i1.184 control status, the ORs of CRC were 2.53 and 1.52 per 1 decile decrease in adjusted
baseline LTL and mtDNA-CN, respectively. In conclusion, LTL and mtDNA-CN were
Received: September 5, 2022
Accepted: December 1, 2022 independent inverse predictors of the 15-year risk of CRC in the Russian cohort. These
Published Online: January 10, findings highlight the relevance for subsequent research to exploit the mechanisms
2023 through which LTL and mtDNA-CN may reflect human health.
Copyright: © 2023 Author(s).
This is an Open Access article
distributed under the terms of the Keywords: Leukocyte telomere length; Mitochondrial DNA copy number; Aging; Cancer;
Creative Commons Attribution Case–control; Population
License, permitting distribution,
and reproduction in any medium,
provided the original work is
properly cited.
Publisher’s Note: AccScience 1. Background
Publishing remains neutral with The world population is expected to reach 8.6 billion people by 2030, with about 1.4
regard to jurisdictional claims in [1]
published maps and institutional billion being over 60 years old . An increase in life expectancy goes hand-in-hand with
affiliations. the aging of population and the aggregation of age-related diseases.

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