Gut bacteria may be factor in rising colorectal cancer incidence among younger adults
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Fusobacterium nucleatum may be partially responsible for the sharp increase in colorectal cancer incidence among individuals aged younger than 45 years, according to preliminary results of an ongoing study presented at Gastrointestinal Cancers Symposium.
“We haven’t seen large genetic differences in colorectal tumors in younger vs. older people, so we think that something in the microbiome may be behind the rise in incidence of colorectal cancer in young people,” Benjamin Adam Weinberg, MD, assistant professor of medicine at Georgetown University and a HemOnc Today Next Gen Innovator, told Healio.
“The approach to [treatment for] younger and older patients is generally the same; [however], studies have shown that younger patients tend to get more aggressive treatments without an improvement in outcomes,” he added.
Rates of colorectal cancer, particularly in the distal colon and rectum, have increased among those aged younger than 45 years despite declines in overall incidence.
Weinberg and colleagues hypothesized that the microbiome may be behind this rise because certain bacteria disrupt colonic luminal integrity and promote inflammation, which leads to oncogenic mutations in colonic epithelial cells.
Specifically, F. nucleatum may promote colorectal cancer by suppressing immune response within the tumor microenvironment, triggering the beta-catenin pathway and inducing chemoresistance due to autophagy.
The researchers analyzed the DNA and microbiome of tumors from 18 younger patients (median age, 39.2 years; range, 18.2-44.6; 61% women) and 13 older patients (median age, 72.8 years; range, 65.9-85; 62% women). They extracted and evaluated DNA using 16S ribosomal gene sequencing.
Primary tumors constituted the vast majority of those analyzed in both groups (94% vs. 100%).
Researchers compared the frequency of F. nucleatum and other bacterial and fungal DNA in tumors of younger and older patients.
Results showed that, among 478 unique bacterial and fungal species detected, F. nucleatum appeared in tumors of five younger patients (28%), including four left-sided tumors and one right-sided tumor, and three older patients (23%), including one left-sided and two right-sided tumors.
Compared with older patients, younger patients had a significantly lower rate of Moraxella osloensis (11% vs. 46% P = .04), another bacterium that has been found to be nearly four times more common in tumors of people aged older than 75 years compared with those aged younger than 45 years.
Researchers observed no significant differences in microbiome diversity between the two groups.
Further studies involving more tumors are needed to determine whether F. nucleatum can fully explain the rising incidence of young-onset colorectal cancer, according to the researchers.
“We are planning to enroll a total of 128 patients to evaluate the F. nucleatum question; here, we present the first 31 patients analyzed,” Weinberg said. “We are also trying to get NCI-biobanked specimens to do the research more expeditiously.” – by John DeRosier
Reference:
Weinberg BA, et al. Abstract 241. Presented at: Gastrointestinal Cancers Symposium; Jan. 23-25, 2020; San Francisco.
Disclosures: Colorectal Cancer Alliance funded this study. Weinberg reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
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Mark Hanna, MD
There is growing evidence that the microbiome may contribute to incidence of disease, its pathogenesis and outcomes of cancer treatment. There also is interest in whether the microbiome has any effect on incidence of complications such as surgical site infections and anastomotic leaks, so this study is very interesting and timely for us in the oncologic community.
It is not yet clear how research into the microbiome will affect practice. Right now, there is some evidence that changes in the microbiome may contribute to differences in cancer incidence and response to treatment.
Certain strains of bacteria have been identified as related to cancer incidence and treatment response. In this study, researchers looked at F. nucleatum, and although the results were not significantly different than other strains, they did find a significant difference in the composition of the microbiome of younger patients with colorectal cancer compared with older patients. .
Additionally, the implications of the microbiome are not based on the presence of certain strains of bacteria over others. Rather, it’s more about the interaction of these bacteria. The presence of one overgrowing bacterium doesn’t necessarily indicate a higher risk for cancer or developing complications. However, the interaction of certain bacteria or the absence of other bacteria may be the answer. Our understanding is still in its infancy, and we still have a lot to learn about this domain.
I do believe there will be greater focus on the microbiome in ongoing clinical research in colorectal cancer. For instance, based on a better understanding of the microbiome, we could in the future screen individuals for colorectal cancer using colonoscopy and take samples of their microbiome to stratify their risks for cancer. We also would be able to screen the microbiome to see if a certain treatment will work for specific patients. This would allow a more tailored precision medicine-based approach to screening and treatment of patients with cancer based on their specific microbiome.
In the surgical domain, despite improved minimally invasive techniques such as laparoscopy and robotics, we continue to struggle in improving other quality metrics such as infections and anastomotic leaks. A consensus is forming around the microbiome as a potential untapped avenue where we may find answers and make improvements. I look forward to seeing more positive results as we move forward.
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