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Fred Hutch Researchers Identify Oral Bacteria That Appear to Play a Role in Certain Colon Cancers

Discovery highlights how ongoing microbiome research points to new opportunities that can lead to development of more effective cancer screening clinical laboratory tests

New research from the Fred Hutchinson Cancer Center in Seattle once again demonstrates that the human microbiome plays a sophisticated role in many biological processes. Microbiologists and anatomic pathologists who diagnose tissue/biopsies will find this study’s findings intriguing.

This breakthrough in colon cancer research came from the discovery that a “subspecies” of a common type of a bacteria that resides in the mouth and causes dental plaque also “shields tumor cells from cancer treatment,” according to NBC News.

The scientists inspected colorectal cancer (CRC) tumors and found that 50% of those examined featured a subspecies of Fusobacterium nucleatum (F. nucleatum or Fn) and that this anaerobic bacterium was “shielding tumor cells from cancer-fighting drugs,” NBC News noted. Many of these tumors were considered aggressive cases of cancer. 

“The discovery, experts say, could pave the way for new treatments and possibly new methods of screening,” NBC News reported.

The Fred Hutchinson Cancer Center scientists published their findings in the journal Nature titled, “A Distinct Fusobacterium Nucleatum Clade Dominates the Colorectal Cancer Niche.”

“Patients who have high levels of this bacteria in their colorectal tumors have a far worse prognosis,” Susan Bullman, PhD (above), who jointly supervised the Fred Hutch research team and who is now Associate Professor of Immunology at MD Anderson Cancer Center, told NBC News. “They don’t respond as well to chemotherapy, and they have an increased risk of recurrence,” she added. Microbiologists and clinical laboratories working with oncologists on cancer treatments will want to follow this research as it may lead to new methods for screening cancer patients. (Photo copyright: Fred Hutchinson Cancer Center.)

Developing Effective Treatments

Susan Bullman, PhD, Associate Professor of Immunology at MD Anderson Cancer Center, who along with her husband and fellow researcher Christopher D. Johnston, PhD, Assistant Professor at Fred Hutchinson Cancer Center, jointly supervised an international team of scientists that examined the genomes of 80 F. nucleatum strains from the mouths of cancer-free patients and 55 strains from tumors in patients with colorectal cancer, according to the National Institutes of Health (NIH). The NIH funded the research.

The researchers targeted a subspecies of F. nucleatum called F. nucleatum animalis (Fna) that “was more likely to be present in colorectal tumors. Further analyses revealed that there were two distinct types of Fna. Both were present in mouths, but only one type, called Fna C2, was associated with colorectal cancer” the NIH wrote in an article on its website titled, “Gum Disease-related Bacteria Tied to Colorectal Cancer.”

“Tumor-isolated strains predominantly belong to Fn subspecies animalis (Fna). However, genomic analyses reveal that Fna, considered a single subspecies, is instead composed of two distinct clades (Fna C1 and Fna C2). Of these, only Fna C2 dominates the CRC tumor niche,” the Fred Hutch researchers wrote in their Nature paper.

“We have pinpointed the exact bacterial lineage that is associated with colorectal cancer, and that knowledge is critical for developing effective preventive and treatment methods,” Johnston told the NIH.

How Bacteria Got from Mouth to Colon Not Fully Understood

Traditionally, F. nucleatum makes its home in the mouth in minute quantities. Thus, it is not fully understood how these bacteria travel from the mouth to the colon. However, the Fred Hutch researchers showed that Fna C2 could survive in acidic conditions, like those found in the gut, longer than the other types of Fna. This suggests that the bacteria may travel along a direct route through the digestive tract.

The study, which focused on participants over 50, comes at a time when colorectal cancer rates are trending upward. Rates are doubling for those under 55, jumping from 11% in 1995 to 20% in 2019. CRC is the second-leading cancer death and over 53,000 will succumb to the disease in 2024, according to NBC News.

Many of the newer diagnoses are in later stages with no clear reason why, and the Fred Hutch scientists are trying to understand how their findings tie into the increase of younger cases of colon cancer.

Bullman says it will be important to look at “whether there are elevated levels of this bacterium in young onset colorectal cancer, which is on the rise globally for unknown reasons,” she told NBC News.

Possibility of More Effective Cancer Screening

There is hope that scientists equipped with this knowledge can develop new and more effective screening and treatment options for colon cancer, as well as studying the microbiome’s impact on other diseases.

On the prevention side, researchers have seen that in mice the addition of Fna “appeared to cause precancerous polyps to form, one of the first warning signs of colorectal cancer, though Bullman added that this causation hasn’t yet been proven in humans.” NBC reported.

Future research may find that screening for Fna could determine if colorectal tumors will be aggressive, NIH reported.

“It’s possible that scientists could identify the subspecies while it’s still in the mouth and give a person antibiotics at that point, wiping it out before it could travel to the colon,” Bullman told NBC News. “Even if antibiotics can’t successfully eliminate the bacteria from the mouth, its presence there could serve as an indication that someone is at higher risk for aggressive colon cancer.”

There is also the thought of developing antibiotics to target a specific subtype of bacteria. Doing so would eliminate the need to be “wiping out both forms of the bacteria or all of the bacteria in the mouth. Further, it’s relevant to consider the possibility of harnessing the bacteria to do the cancer-fighting work,” NBC noted.

“The subtype has already proven that it can enter cancer cells quite easily, so it might be possible to genetically modify the bacteria to carry cancer-fighting drugs directly into the tumors,” Bullman told NBC News.

Further studies and research are needed. However, the Fred Hutch researchers’ findings highlight the sophistication of the human microbiome and hint at the potential role it can play in the diagnosis of cancer by clinical laboratories and pathology groups, along with better cancer treatments in the future.

—Kristin Althea O’Connor

Related Information:

A New Type of Bacteria was Found in 50% Of Colon Cancers. Many Were Aggressive Cases.

Gum Disease-related Bacteria Tied to Colorectal Cancer

A Distinct Fusobacterium Nucleatum Clade Dominates the Colorectal Cancer Niche

Clinical Trial Shows New Laboratory Developed Blood Test 83% Effective at Detecting Colorectal Cancer

Accurate blood-based clinical laboratory testing for cancer promises to encourage more people to undergo early screening for deadly diseases

One holy grail in diagnostics is to develop less-invasive specimen types when screening or testing for different cancers. This is the motivation behind the creation of a new assay for colorectal (colon) cancer that uses a blood sample and that could be offered by clinical laboratories. The data on this assay and its performance was featured in a recent issue of the New England Journal of Medicine(NEJM).

The company developing this new test recognized that more than 50,000 people will die in 2024 from colon cancer, according to the American Cancer Society. That’s primarily because people do not like colonoscopies even though the procedure can detect cancer in its early stages. Similarly, patients tend to find collecting their own fecal samples for colon cancer screening tests to be unpleasant.

But the clinical laboratory blood test for cancer screening developed by Guardant Health may make diagnosing the deadly disease less invasive and save lives. The test “detects 83% of people with colorectal cancer with specificity of 90%,” a company press release noted.

“Early detection could prevent more than 90% of colorectal cancer-related deaths, yet more than one third of the screening-eligible population is not up to date with screening despite multiple available tests. A blood-based test has the potential to improve screening adherence, detect colorectal cancer earlier, and reduce colorectal cancer-related mortality,” the study authors wrote in the NEJM.

As noted above, this is the latest example of test developers working to develop clinical laboratory tests that are less invasive for patients, while equaling or exceeding the sensitivity and specificity of existing diagnostic assays for certain health conditions.

“I do think having a blood draw versus undergoing an invasive test will reach more people, My hope is that with more tools we can reach more people,” Barbara H. Jung, MD (above), President of the American Gastroenterological Association, told NPR. Clinical laboratory blood tests for cancer may encourage people who do not like colonoscopies to get regular screening. (Photo copyright: American Gastroenterology Association.)

Developing the Shield Blood Test

Colorectal cancer is the “third most common cancer among men and women in the US,” according to the American Gastrological Association (AGA). And yet, millions of people do not get regular screening for the disease.

To prove their Shield blood test, Guardant Health, a precision oncology company based in Redwood City, Calif., enrolled more than 20,000 patients between the ages of 45-84 from across the US in a prospective, multi-site registrational study called ECLIPSE (Evaluation of ctDNA LUNAR Assay In an Average Patient Screening Episode).

“We assessed the performance characteristics of a cell-free DNA (cfDNA) blood-based test in a population eligible for colorectal cancer screening. The coprimary outcomes were sensitivity for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions) relative to screening colonoscopy. The secondary outcome was sensitivity to detect advanced precancerous lesions,” the study authors wrote in the NEJM.

In March, Guardant completed clinical trials of its Shield blood test for detecting colorectal cancer (CRC) in men and women. According to the company press release, the test demonstrated:

  • 83% sensitivity in detecting individuals with CRC.
  • 88% sensitivity in detecting pathology-confirmed Stages I-III.

Additionally, the Shield test showed sensitivity by stage of:

  • 65% for pathology-confirmed Stage I,
  • 55% for clinical Stage I,
  • 100% for Stage II, and
  • 100% for Stage III.

“The results of the study are a promising step toward developing more convenient tools to detect colorectal cancer early while it is more easily treated,” said molecular biologist and gastroenterologist William M. Grady, MD, Medical Director, Gastrointestinal Cancer Prevention Program at Fred Hutchinson Cancer Center and corresponding author of the ECLIPSE study in the press release. “The test, which has an accuracy rate for colon cancer detection similar to stool tests used for early detection of cancer, could offer an alternative for patients who may otherwise decline current screening options.”

Are Colonoscopies Still Needed?

“More than three out of four Americans who die from colorectal cancer are not up to date with their recommended screening, highlighting the need for a more convenient and less invasive screening method that can overcome barriers associated with traditional options,” Daniel Chung, MD, gastroenterologist at Massachusetts General Hospital and Professor of Medicine at Harvard Medical School, said in the Guardant press release.

Barbara H. Jung, MD, President of the American Gastroenterological Association, says that even if Guardant’s Shield test makes it to the public the “dreaded colonoscopy” will still be needed because the procedure is used to locate and test polyps. “And when you find those you can also remove them, which in turn prevents the cancer from forming,” she told NPR.

There is hope that less invasive clinical laboratory testing will encourage more individuals to get screened for cancer earlier and regularly, and that the shift will result in a reduction in cancer rates.

“Colorectal cancer is highly treatable if caught in the early stages,” said Chris Evans, President of the Colon Cancer Coalition, in the Guardant press release.

Guardant Health’s ECLIPSE study is a prime example of the push clinical laboratory test developers are making to create user-friendly test options that make it easier for patients to follow through with regular screening for early detection of diseases. It echoes a larger effort in the medical community to think outside the box and come up with creative solutions to reach wider audiences in the name of prevention.

—Kristin Althea O’Connor

Related Information:

Guardant Health ECLIPSE Study Data Demonstrating Efficacy of Shield Blood-based Test for Colorectal Cancer Screening to be Published in The New England Journal of Medicine

A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening

Guardant Health Announces Positive Results from Pivotal ECLIPSE Study Evaluating a Blood Test for the Detection of Colorectal Cancer

A Simple Blood Test Can Detect Colorectal Cancer Early, Study Finds

Key Statistics for Colorectal Cancer

Colorectal Cancer Facts and Statistics

Cancer Stat Facts: Colorectal Cancer

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