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Differences in Right vs Left Colon in Black vs White Individuals

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The right colon appears to age faster in Black people than in White people, perhaps explaining the higher prevalence of right-side colon cancer among Black Americans, according to results from a biopsy study.

The findings were published online December 30 in the Journal of the National Cancer Institute.

For the study, investigators analyzed colon biopsy specimens from 128 individuals who underwent routine colorectal screening.

The researchers compared DNA methylation levels in right and left colon biopsy samples from the same patient. They then assigned epigenetic ages to the tissue samples using the Hovarth clock, which estimates tissue age on the basis of DNA methylation.

DNA methylation is influenced by age and environmental exposures. Aberrant DNA methylation is a hallmark of colorectal cancer, the researchers explain.

The epigenetic age of the right colon of the 88 Black patients was 1.51 years ahead of their left colon; the right colon of the 44 White patients was epigenetically 1.93 years younger than their left colon.

The right colon was epigenetically older than the left colon in 60.2% of Black patients; it was younger in more than 70% of White patients.

A unique pattern of DNA hypermethylation was found in the right colon of Black patients.

“Our results provide biological plausibility for the observed relative preponderance of right colon cancer and younger age of onset in African Americans as compared to European Americans,” comment the investigators, led by Matthew Devall, PhD, a research associate at the Center for Public Health Genomics at the University of Virginia, Charlottesville, Virginia.

“Side-specific colonic epigenetic aging may be a promising marker to guide interventions to reduce CRC [colorectal cancer] burden,” they suggest.

If these findings are “corroborated in African Americans in future studies, these results could potentially explain racial differences in the site predilection of colorectal cancers,” said Amit Joshi, MBBS, PhD, and Andrew Chan, MD, gastrointestinal molecular epidemiologists at Harvard University, Boston, Massachusetts, in an accompanying editorial.

However, “it is not clear if the higher epigenetic aging measured using the Horvath clock…directly translates to a higher risk of colorectal cancer,” they note.

Some differences between the Black patients and the White patients in the study could explain the methylation differences, they point out. A higher proportion of Black patients smoked (37.5% vs 15%), and Black patients were younger (median age, 55.5 years, vs 61.7 years). In addition, the study included more Black women than White women (67% vs 58%), and body mass indexes were higher for Black patients than White patients (31.36 kg/m2 vs 28.29 kg/m2).

“One or more of these factors, or others that were not measured, may be linked to differential methylation in the right compared with left colon,” the editorialists write.

Even so, among the Black patients, almost 70% of differentially methylated positions in the right colon were hypermethylated, compared to less than half in the left colon. These included positions previously associated with colorectal cancer, aging, and ancestry, “suggesting a role for genetic variation in contributing to DNA methylation differences in AA right colon,” the investigators say.

The work was supported the National Cancer Institute Cancer, the Case Comprehensive Cancer Center, and the University of Virginia Cancer Center. The authors and editorialists have disclosed no relevant financial relationships.

J Natl Cancer Inst. Published online December 30, 2020. Abstract, Editorial

M. Alexander Otto is a physician assistant with a master’s degree in medical science, and an award-winning medical journalist who has worked for several major news outlets before joining Medscape, including McClatchy and Bloomberg. He is an MIT Knight Science Journalism fellow. Email: [email protected]

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