5 Potentially Non-invasive Colorectal Cancer Screening Methods

When it comes to detecting colorectal cancer, a colonoscopy is still considered the gold standard as it allows doctors to view the inside of the colon in real time. Besides colonoscopies, stool-based tests are quick and inexpensive screening methods that are also available, however, each of these have their drawbacks.

For one, stool-based tests aren’t the most sensitive or conclusive, and at times could test false positives due to other underlying conditions besides colorectal cancer. Colonoscopies, while reliable, are considered invasive and can cause discomfort and minor internal trauma to the patient.

The downsides of these screening methods often mean that patients or individuals who are potentially at risk of colorectal cancer are less inclined to go for screening, lest they have to put up with the discomfort. As such, new, non-invasive screening methods may help encourage sooner and more frequent testing, both of which have potentially lifesaving outcomes.

Compared to having a long tube inserted into your body, having a small amount of blood drawn from you is arguably a much less invasive way to screen for colorectal cancer. As it stands, there is already one FDA-approved cancer blood test called Epi proColon™, which looks for methylated SEPT9 genes in circulating tumor DNA (ctDNA) that is often found in the blood.

Aside from testing components found in the blood, testing the DNA found in white blood cells may also be a potential screening test in future. Specifically, peripheral blood mononuclear cells — immune cells that originate from the bone marrow that contain a single, round nucleus — that are found in circulation can also be tested for methylated SEPT9 genes.

The use of non-coding genetic material as a biomarker for cancer is not new either. In fact, there are already successful cases of such cancer screening tests currently available, such as GASTROClear, which detects the presence of microRNA (miRNA) in the blood to screen for gastric cancer.
However, Piwi-Interacting RNA (piRNA) is another type of genetic material with untapped potential as a colorectal cancer biomarker.

piRNA form complexes with proteins from the piwi family, and these complexes are largely responsible for epigenetic and post-transcriptional silencing (that is, turning off a gene after a protein has been made). Studies have shown that piRNA expression is often deregulated or impaired in different cancers, including colorectal cancer.

Given that piRNA is small, highly stable and easy to detect, monitoring the levels of piRNA can potentially be a strong diagnostic and predictive biomarker for colorectal cancer.

Gut flora and bacteria play important roles in our digestive tract, and examining the gut microbiota can provide an indication of colorectal cancer. This is especially true since it has been found that compared to healthy individuals, colorectal cancer patients have lower gut bacteria species diversity, a lower quantity of bacteria that confer protective qualities and an increased presence of procarcinogenic bacteria.

Particularly, the presence of F. nucleatum has so far identified colorectal cancer patients with almost 70% sensitivity and about 77% specificity. As a future screening tool, the gut bacteria population can be sampled by examining the patient's stool sample.

We’ve all heard of the breathalyzer test to estimate blood alcohol levels. Now, it may also be possible to detect colorectal cancer through exhaled breath by testing for specific volatile organic compounds (VOCs).

VOCs are organic chemicals that arise as a result of pathophysiological metabolic processes, and many cancer-related metabolic processes produce these chemicals. VOCs can be found in many different body secretions including stool and urine, but is most easily tested in the exhaled breath, in which case would be known as a breath biopsy.

VOCs are typically presented in higher levels in patients with colorectal cancer compared to healthy individuals, and the ease of sample testing means that it may be possible for a device to provide a binary yes-no result quickly and conveniently.

Similar to the breathalyzer test, urine tests are also commonplace screening methods that have different applications. Soon, urine may also be used to detect the presence of colorectal cancer by specifically screening for the presence of ctDNA.

While ctDNA can be found in various body fluids including the blood, colorectal cancer in particular has a high tumor cell loss factor, that is, many of the newly produced cells as a result of carcinogenesis die or fail to divide, and is often discharged through the blood or other body fluids.

One study explored the use of methylated NDRG4 gene as a colorectal cancer biomarker found in both the stool and urine. By using nested methylation-specific PCR and denaturing high-performance liquid chromatography (DHPLC) on DNA samples collected from patients, the mRNA form of the NDRG4 gene was present not only in colorectal carcinoma tissue, but also blood, stool and urine.