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

Finally, we assessed the association of CRC with Wentzensen et al., in their meta-analysis, have indicated
generated LTL and mtDNA-CN values, preliminary an inverse association between LTL and CRC risk in a
adjusted for multiple covariates, and their interaction with retrospective case–control study .
[41]
case–control status. The results were weaker with OR of On the other hand, our findings are opposite to the
CRC 2.53 (95% CI: 2.16 – 2.97) per 1 decile decrease in fully data obtained from a prospective study in Singapore
adjusted baseline LTL (Supplementary File, Table S3) and (n = 26.000, 12-year follow-up) , which has reported a
[42]
with OR of CRC 1.52 (1.39 – 1.65) per 1 decile decrease in positive association between LTL and CRC risk, with a
fully adjusted baseline mtDNA-CN (Supplementary File, HR of 1.32 (95% CI: 1.08 – 1.62) for the top quartile of
Table S4). telomere length versus bottom quartile. In a meta-analysis
4. Discussion of 28 prospective studies (2 on CRC), no associations were
reported between LTL and CRC risk . Similarly, the
[21]
The present nested case-control study included individuals pooled results of eight prospective studies have revealed
with incident CRC (cases) and age and sex frequency- that LTL is associated with neither a better or poorer
matched controls from a Novosibirsk population cohort prognosis of CRC patients . Interestingly, in a Mendelian
[43]
(Russia). The carriers of shorter telomeres had an increased randomization study (MRS) of the UK Biobank data
15-year risk of incident CRC with adjusted OR 3.2 per 1 (7.5-year follow-up, n = 261,837), genetically determined
decile decrease in LTL. Lower mtDNA-CN was associated longer telomeres were found to be associated with a
with an increased risk of incident CRC with adjusted modestly elevated risk of pooled cancer. However, the risk
OR 1.7 per 1 decile decrease in mtDNA-CN. The risk of CRC was found to be below 1 among those with longer
coefficients of CRC were attenuated to OR 2.53 per 1 decile telomeres, while remaining statistically insignificant .
[22]
decrease in adjusted baseline LTL and OR 1.52 per 1 decile A recent MRS using genetic risk score for LTL has found
decrease in adjusted baseline mtDNA-CN. that short LTL score is related to a reduced risk of nine
A number of epidemiological studies, with varying types of cancer (not including CRC) in the UK Biobank
samples and designs, have explored the associations dataset, but there has been an observation that is suggestive
between LTL and the risk of cancer, but the results are of an association between short LTL score and a high death
inconsistent [14,20-23] . Specifically for CRC incidence and hazard of rectum adenocarcinoma in The Cancer Genome
[23]
mortality, both negative and positive relationships, Atlas (TCGA) dataset , of which the latter is in line with
U-shaped, and absence of association with LTL have been our findings.
reported. Concerning the alternations of mtDNA in relation
[24]
Our findings of an inverse relationship between to cancer, different results have been reported . For a
baseline LTL and CRC incidence are consistent with the number of cancer types, an inverse, multidirectional, or
prospective Bruneck study , a case–control study in nonlinear relationship with mtDNA has been reported
[35]
[36]
China , and are in line with the CRC mortality findings (colorectal, breast, kidney, and lung) [25,27] ; the absence of
in two meta-analyses [37,38] . In the Bruneck study with a distinction between tumor tissue and adjacent unaffected
10-year follow-up, the adjusted hazard ratio was 1.56 (95% tissue has also been reported (colorectal, kidneys, pancreas
[26]
CI: 1.32 – 1.85) for CRC incidence and 1.88 (95% CI: 1.48 and thyroid glands, prostate, stomach, and uterus) .
– 2.40) for CRC mortality per 1 SD shorter baseline LTL . Our results of an inverse association between baseline
[35]
In a case-control study of a Chinese population, shorter mtDNA-CN and CRC incidence are in line with the
LTL was modestly associated with higher risk of CRC (OR Shanghai Women’s Health Study and, partly, with a
[44]
per LTL tertile 1.13; 95% CI: 1.00 – 1.28) . In a study recent prospective Swedish study . In a case–control
[45]
[36]
conducted by Kroupa et al., shorter telomeres were found design for CRC established on a population sample (n=
in CRC tumor tissue than in adjacent mucosa . This 444/1,423 women, >9 years follow-up) under the Shanghai
[39]
finding is supported by evidence from recent studies . Women’s Health Study, the researchers found an inverse
[40]
Zhang et al., in a meta-analysis based on 45 prospective association between baseline mtDNA-CN and incident
studies of incident cancer (2 for CRC), have shown that CRC with adjusted OR = 1.26 (95% CI: 0.93 – 1.70) and
short telomeres are related to increased CRC mortality, 1.44 (95% CI: 1.06 – 1.94) for the middle and bottom tertiles
with an RR of 2.54 (95% CI: 1.73 – 3.72) for short telomere of mtDNA-CN values, respectively . In a prospective
[44]
length compared to long telomere length as dichotomized Swedish study (women, 15.2 years follow-up), baseline LTL
[37]
variable . In another meta-analysis of prospective and and mtDNA-CN were not associated with the prevalence
retrospective studies, short LTL was associated with poorer and incidence of a digestive cancer as a cumulative
survival for CRC (HR = 2.01; 95% CI: 1.46 – 2.77) . category (including CRC). However, mtDNA-CN (but not
[38]
Volume 2 Issue 1 (2023) 8 https://doi.org/10.36922/gtm.v2i1.184