DNA Methylation Indicates Left and Right Colon Do Not Age at Same Rate

Human colon
Racial differences in age of onset and laterality of colorectal cancer are well documented. This study examines race- and side-specific differences in epigenetic aging of normal colon.

Epigenetic-specific aging has been found to occur at differing speeds along the left and right colon and is associated with ethnicity. These findings, from an analysis of DNA methylation, were published in the Journal of the National Cancer Institute.

Researchers from the University of Virginia assessed right and left normal colon biopsy specimens from 128 individuals for methylation changes, which likely alter gene expression. They only considered sites with more than 5% changes in mean methylation as significant.

Study participants were Black (n=88) or White of European ancestry (n=40).

The researchers correlated chronologic ages and methylation-based DNA ages. The correlation was stronger among the White participants (left: r =0.85; right: r =0.86) than the Black participants (left: r =0.67; right: r =0.66), indicating a more rapid aging process among Black individuals.

The investigators observed methylation-based age to be accelerated in the left colon among White participants (difference, 1.93 years; 95% CI, 0.65-3.21; P =.004) as was the right colon among Black participants (difference, 1.51 years; 95% CI, 0.62-2.4; P =.001).

Compared between ethnic groups, White participants exhibited increased methylation in the left colon (2.74; 95% CI, 1.21-4.44 years; P =.001), and more Black participants had epigenetically older right colons (60.2% vs 27.5%; P =.001).

The researchers observed 14,547 differentially methylated positions (DMPs), 558 and 456 of which were ethnicity-specific in the left and right colon, respectively. In the right colon, 69.5% of DMPs were hypermethylated among Black individuals (P =3.67 × 10−7).

This study was likely limited by its small and unbalanced sample sizes, indicating future studies with larger samples are needed to verify these findings.

These data indicated ethnicity and location-specific hypermethylation of DNA may be driving the patterns and rates of colorectal cancer among Black and White patients, in which Black patients have higher rates of right colon lesions occurring at younger ages compared with White patients. These differentially methylated positions may be valuable biomarkers for cancer and help guide interventions.


Devall M, Sun X, Yuan F, et al. Racial disparities in epigenetic aging of the right vs left colon. J Natl Cancer Inst. Published online December 30, 2020. doi:10.1093/jnci/djaa206