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

Malyutina, Sofia; Maximov, Vladimir; Chervova, Olga; Orlov, Pavel; Voloshin, Vitaly; Ryabikov, Andrew; Voevoda, Mikhail; (2023) Leukocyte telomere length and mitochondrial DNA copy number association with colorectal cancer risk in an aging population. Global Translational Medicine , 2 (1) , Article 184. 10.36922/gtm.v2i1.184. Green open access

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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 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.

Type: Article
Title: Leukocyte telomere length and mitochondrial DNA copy number association with colorectal cancer risk in an aging population
Open access status: An open access version is available from UCL Discovery
DOI: 10.36922/gtm.v2i1.184
Publisher version: https://doi.org/10.36922/gtm.v2i1.184
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Leukocyte telomere length, Mitochondrial DNA copy number, Aging, Cancer, Case–control, Population
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/10163050
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