Although the overall incidence rate of colorectal cancer is falling in the U.S., it is increasing in young adults, particularly young African Americans. The American Cancer Society reports that African Americans are 20% more likely to develop colorectal cancer and 40% more likely to die from it. A team of scientists at UVA Cancer Center led by cancer researcher and family physician Li Li, MD, PhD, is actively working to find not only an explanation for this widening disparity, but also a path to prevention.
The Aging Colon
Advanced age is a risk factor for many diseases, including colorectal cancer, Li reminds. Yet we now know a patient’s birth age is only part of the equation. Early research has shown that we also have to consider biological age of tissues to determine the health of an organ. This background discovery drove Li’s efforts to pinpoint how the colon ages — more specifically, how each side of the colon ages in Caucasians and African Americans. That distinction was key to a critical discovery.
“We’ve come to realize that left- and right-sided colorectal cancers are two distinctly different diseases even though they are both colon cancers. Right-sided colon cancer is more aggressive and has worse outcomes,” says Li, leader of the Cancer Control and Population Health program at UVA Cancer Center. “African Americans tend to have more right-sided cancers compared to whites, who more often develop the disease on the left side.”
With support from a National Cancer Institute Cancer Disparities SPORE P20 Planning Grant for research, Li and his team launched a study to find out why African Americans are at increased risk for this more deadly right-side colon cancer.
The researchers collected tissue samples from the normal, right- and left-side colons of 128 patients — 88 Black and 40 Caucasian. They then performed epigenome DNA methylation analysis of the tissue, looking at the epigenetic changes that come with age. What they found was that the right side of the colon in most African Americans had a unique pattern of hypermethylation, affecting gene expression. It was, in essence, like the right side of the colon was old beyond its years.
“For Blacks in the study, the right side of the colon aged much faster than the left in the same person,” says Li. “The right-side colon was about 1.5 years older than the left.”
This, the researchers believe, could contribute to African Americans’ increased cancer risk and could explain why they are more likely to develop cancerous lesions on the right side.
The research could also explain why younger people of European descent are more likely to develop lesions on the left side – the side that tends to age faster in that group. “For white patients, our analysis showed it was the left side of the colon that aged faster; it was about 1.9 years older than the right,” says Li.
“This discovery provides novel insight of the mechanistic underpinning for the observed racial disparities in age-of-onset and anatomical distribution of colon neoplasia. Side-specific biological aging of the colon might emerge as a novel biomarker to guide the development of personalized prevention and intervention strategies,” he adds.
A Step Toward Prevention
The challenge, of course, is understanding why these differences exist. “What drives this distinction across the two races? That’s where we are now,” says Li. “We need to understand why this happens; what is the underlying driver for the racial disparity?”
To address these outstanding questions, Li and his team are in the process of launching a new, larger study he hopes will provide insight into how environment and lifestyle play a role in colon cancer rates.
“We aim to begin recruiting another cohort of patients for this study soon,” he says. “We will prioritize the inclusion of patients who come from rural areas and who identify as Black or minority so that we reach that data set. This way we can validate the findings we already have, but also start to acquire more omics-based data.”
The study will evaluate a patient’s upper stream social environment, stress and individual lifestyle factors such as diet and exercise, but will also drill down into other mechanisms that may be involved in the aging process, such as metabolism and the makeup of the microbiome. “This research focuses on the intersection of biology and environmental factors in the population,” says Li.
“In addition to asking patients about their diet, physical activity, sleep habits, stress and living environment. We also hope to take biosamples — hair, fingernails, saliva — that will allow us to look for biological biomarkers and trace elements from the environment. We believe the outcome will have a lot of implications for prevention.”
Li and his team published their findings on the aging colon in the Journal of the National Cancer Institute.