From the AGA Journals

New blood test could reshape early CRC screening



A simple blood test that looks for a combination of specific RNA snippets may become a novel way to screen for early-onset colorectal cancer, suggests a new study published online in Gastroenterology.

Researchers identified four microRNAs that together comprise a signature biomarker that can be used to detect and diagnose the presence of colorectal cancer from a liquid biopsy in a younger population.

MicroRNAs, or miRNAs, are small RNA molecules that do not encode proteins but are used instead to regulate gene expression. The study authors developed and validated a panel that detects four miRNAs occurring at higher levels in plasma samples from patients with early-onset colorectal cancer, with high sensitivity and specificity.

“The point would be to use this test as a routine part of annual healthcare, or for people in high-risk families every 6 months,” study senior author Ajay Goel, PhD, MS, chair of the department of molecular diagnostics and experimental therapeutics at the City of Hope Comprehensive Cancer Center, Duarte, Calif., said in an interview.

“It’s affordable, it can be done easily from a small tube of blood, and as long as that test stays negative, you’re good,” Dr. Goel said, because even if patients miss a test, the next one, whether it’s 6 months or a year later, will catch any potential cancer.

“Colon cancer is not going to kill somebody overnight, so this should be used as a precursor to colonoscopy. As long as that test is negative, you can postpone a colonoscopy,” he said.

Andrew T. Chan, MD, MPH, a professor of medicine at Harvard Medical School and vice chair of gastroenterology at Massachusetts General Hospital, both in Boston, who was not involved in the research, said in an interview that the findings are exciting.

“It would be really value-added to have a blood-based screening test,” Dr. Chan said, adding that researchers have pursued multiple different avenues in pursuit of one. “It’s very nice to see that area progress and to actually have some evidence that microRNAs could be a potential biomarker for colorectal cancer.”

Screening now insufficient for early-onset disease

The U.S. Preventive Services Task Force recently lowered the recommended age to 45 years to begin screening for colorectal cancer. Part of the rationale for the change came from the rising rates of early-onset colorectal cancer, a distinct clinical and molecular entity that tends to have poorer survival than late-onset disease, the authors noted.

Early-onset disease, occurring primarily in people under 50 without a family or genetic history of colorectal cancer, now makes up about 10%-15% of all new cases and continues to rise, they write.

“Early-onset colorectal cancer patients are more likely to exhibit an advanced stage tumor at initial presentation, distal tumor localization, signet ring histology, and a disease presentation with concurrent metastasis,” the authors wrote. “This raises the logistical clinical concern that, since the tumors in early-onset colorectal cancer patients are often more aggressive than those with late-onset colorectal cancer, a delayed diagnosis could have a significant adverse impact and can lead to early death.”

Yet current screening strategies are insufficient for detecting enough early-onset cases, the authors assert.

Colonoscopies are invasive, carry a risk for complications, and are cost- and time-prohibitive for people at average risk. Meanwhile, existing fecal and blood tests “lack adequate diagnostic performance for the early detection of colorectal cancer, especially early-onset colorectal cancer, as these assays have yet to be explored or developed in this population,” they wrote.

The ideal “diagnostic modality should preferably be acceptable to healthy individuals, inexpensive, rapid, and preferably noninvasive,” they note.


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