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

ratios (ORs) of CRC per 1 decile decrease in LTL and ORs of CRC risk per 1 decile decrease in adjusted LTL and
mtDNA-CN as continuous variables. Incident CRC case mtDNA-CN as continuous variables.
status was the dependent variable. Model 1 was adjusted
for baseline age and sex; Model 2 included additional 3. Results
adjustments for smoking, BMI, systolic blood pressure 3.1. Basic phenotype characteristics of studied
(SBP), and TC; Model 3 was additionally controlled by the groups
level of education.
Table 1 presents the basic characteristics of the studied
Third, we conducted several sensitivity analyses. Analysis case and control.
stratified by sex was repeated based on the same models, and
we conducted analyses separately for CRC at different sites Participants with incident CRC were somewhat older;
(colon and rectal). To eliminate the potential reverse effect they had higher SBP, serum glucose level, and waist/hip
of an early cancer stage on the reduction of biomarkers’ ratio but similar BMI; they were also more likely to have
values, we excluded cancer cases with onset (i) within the hypertension and diabetes mellitus type 2; in addition,
first 2 years from the baseline and (ii) within the first 8 years their level of education was lower compared with the
from the baseline (i.e., below the median period value), and control group; and women with CRC were more likely to
repeated two variants of logistic regression analysis using be in menopause.
the same covariates and models as above. In a structure of incident CRC, the proportion of
The adjusted LTL and mtDNA-CN values were then colon cancer was 66%, rectal cancer was 32%, and the
generated to incorporate the possible non-linear joint combination of both sites was 2%. The mean (SD; median)
influence of the covariates and case–control status. This onset age of cancer as registered was 68.5 (8.01; 69.7);
was done by adding extra interaction terms between the period between the time blood was drawn and the
case–control and every covariate into the linear regression identification of incident CRC was 7.74 years (4.53; 7.92).
analyses of LTL or mtDNA-CN (dependent variable); The mean (SD; median) of baseline LTL and
for example, case-control status, baseline age, and the mtDNA-CN was 1.27 (0.48; 1.26) and 1.23 (0.49; 1.12),
interaction term between case-control and age. This was respectively. The baseline LTL and mtDNA-CN values
repeated for every covariate, including baseline age, sex, were lower among cases compared to controls: 0.61 (0.31)
smoking, BMI, SBP, TC, education, waist-hip ratio (WHR), versus 1.39 (0.39), P < 0.001 for LTL; and 0.87 (0.29) versus
and glucose level. The adjusted LTL and mtDNA-CN values 1.30 (0.49), P < 0.001 for mtDNA-CN (Figure 1). Both
were generated (i.e., adjusted for baseline age and sex; biomarkers were correlated well between themselves and
controlled for age, sex, smoking, BMI, SBP, TC, education; negatively correlated with baseline age. The correlation
and, additionally adjusted for WHR and glucose level). coefficient between LTL and baseline age was −0.211,
Subsequently, we applied logistic regression to evaluate the P < 0.001; between mtDNA-CN and age was −0.086,

Figure 1. Boxplot of leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-CN) values in cases of colorectal cancer and control
groups (cases/controls: n = 146/799 for LTL and n = 146/785 for mtDNA-CN).

Volume 2 Issue 1 (2023) 5 https://doi.org/10.36922/gtm.v2i1.184