Researchers have found that the bacteria, fungi, and viruses within the tumors of patients with colorectal cancer varied significantly depending on whether they were diagnosed with early-onset or late-onset disease, according to new findings presented by Weinberg et al at the 2023 ASCO Annual Meeting (Abstract 3530). The results of the study may help researchers better understand why more individuals aged 45 years and younger are developing colorectal cancer, particularly those who have no known identifiable risk factors for the disease.
Background
Despite the declining rates of colorectal cancer among individuals aged over 55 years—partially the result of more screenings with colonoscopies that are capable of finding and removing polyps before they become cancerous—rates of colorectal cancer among individuals younger than 55 years have been increasing. Nearly double the number of younger individuals are being diagnosed with colorectal cancer compared with the amount from a decade ago, with the incidence rate rising from 11% in 1995 to 20% in 2020.
“Younger [patients] with colorectal cancer have more biologically aggressive cancers and whatever survival benefit they have by being younger is outweighed but the more aggressive tumor biology. We also know that for the most part, genetics doesn’t explain the recent rise in young-onset disease,” stressed lead study author Benjamin Adam Weinberg, MD, Associate Professor of Medicine in the Division of Hematology and Oncology at the Lombardi Comprehensive Cancer Center at Georgetown University. “But we have trillions of bacteria residing in our body—including in our gut—some of which are implicated in the development of colorectal cancer. [H]ence, we think the microbiome may be an important factor in the development of the disease as it is involved in the interplay between an [individual’s] genetics, environment, diet, and immune system,” he added.
Researchers have known for a while that certain microbes can disturb the lining of the colon and promote tissue inflammation. This can result in DNA mutations in the colon cells and lead to cancer. Researchers also know that one type of bacterium, Fusobacterium nucleatum, can promote cancerous growth by suppressing immune responses in the colon.
Study Methods and Results
In the new study, the researchers sought to better understand the role of the microbiome and how its influence may vary depending on the age of cancer onset by analyzing the DNA and tumor microbiomes of 36 patients with colorectal cancer who were diagnosed with early-onset disease before the age of 45 as well as those of 27 patients who were diagnosed with late-onset disease after the age of 65.
In both groups, the researchers identified 917 unique bacterial and fungal species in the tumors. One of the most common bacteria they found was F nucleatum, which appeared equally in about 30% of both patients with early- and late-onset disease. Additionally, the researchers discovered differences between the two groups—including that Cladosporium sp. was found more commonly in early-onset disease; whereas Pseudomonas luteola, Ralstonia sp., and Moraxella osloensis were seen more commonly in late-onset disease. In terms of composition, Clostridium perfringens, Escherichia coli, Leptotrichia hofstadii, Mycosphaerella sp., Neodevriesia modesta, Penicillium sp., and Leptosphaeria sp. each made up 11% of the microbiome in patients with late-onset disease; however, these organisms were not detected in patients with early-onset disease.
Conclusions
The researchers hope that with the current data, and with future efforts to collect more samples, they can expand their research efforts to continue exploring the relationship between the microbiome and other factors that contribute to colorectal cancer.
“Because we have tumor genetic data and diet questionnaire results from many of our patients, we hope to explore more relationships and other aspects of how the microbiome impacts colorectal cancer progression in the future,” Dr. Weinberg explained. “We are also interested in the circulating microbiome, such as bacteria that could be picked up in a blood sample, and how this correlates with bacteria in the gut and in the tumor,” he concluded.
Disclosure: For full disclosures of the study authors, visit meetings.asco.org.
