AccScience Publishing / GTM / Volume 2 / Issue 1 / DOI: 10.36922/gtm.v2i1.184

Leukocyte telomere length and mitochondrial DNA copy number association with colorectal cancer risk in an aging population

Sofia Malyutina1* Vladimir Maximov1 Olga Chervova2 Pavel Orlov1 Vitaly Voloshin3 Andrew Ryabikov1 Mikhail Voevoda1 Tatiana Nikitenko1
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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
Global Translational Medicine 2023, 2(1), 184
Submitted: 5 September 2022 | Accepted: 1 December 2022 | Published: 10 January 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( )

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 an inverse association of LTL and mtDNA-CN baseline values with the 15-year risk of incident CRC. Carriers of shorter telomeres had an increased 15-year risk of incident CRC with adjusted OR 3.2 (95% CI: 2.56 – 3.87, P < 0.001) per 1 decile decrease in LTL, independent of baseline age, sex, smoking, body mass index, blood pressure, lipid levels, and education. Similarly, lower mtDNA-CN was associated with the higher risk of incident CRC with adjusted OR 1.7 (95% CI: 1.12 – 1.89, P < 0.001) per 1 decile decrease in mtDNA-CN, independent of the aforementioned factors. Using the modified values of LTL and mtDNA-CN adjusted for multiple factors and their interactions with a case–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 independent inverse predictors of the 15-year risk of CRC in the Russian cohort. These findings highlight the relevance for subsequent research to exploit the mechanisms through which LTL and mtDNA-CN may reflect human health.

Leukocyte telomere length
Mitochondrial DNA copy number
RSF grant

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Conflict of interest
The authors declare no conflict of interest.
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Global Translational Medicine, Electronic ISSN: 2811-0021 Published by AccScience Publishing