Dr Marshall on the Potential Role of the Microbiome in Early-Onset CRC

"[Approximately] 90% of these tumors are [located] in the left side distal colon. This, to me, comes back to the microbiome. We're seeing the emergence of this population which looks to be its own disease."

John L. Marshall, MD, the chief of Hematology and Oncology, director of the Otto J. Ruesch Center for the Cure of Gastrointestinal Cancers and a professor of medicine and oncology at Georgetown Lombardi Comprehensive Cancer Center, discussed whether specific microbiome configurations or environmental triggers concentrated in the distal colon could explain why patients with early-onset colorectal cancer (EO-CRC) are showing increasing left-sided tumor predominance.

In honor of CRC Awareness Month, Marshall joined his colleague, Christopher Lieu, MD, to examine the potential drivers behind the rising incidence of CRC in younger populations. Although the oncology community has seen significant success in treating and curing traditional colorectal cancer, the emergence of EO-CRC represents a distinct challenge that increasingly appears to be its own unique disease entity.

A defining characteristic of EO-CRC is the overwhelming predominance of left-sided, distal tumors, Marshall stated. Although traditional CRC typically presents with approximately 40% of tumors on the right side and 60% on the left, the distribution in younger patients is vastly different, he asserted. In his experience, most of these tumors are located in the left distal colon, frequently occurring at the rectosigmoid junction. This striking clinical observation suggests that the biology and origin of EO-CRC are fundamentally different from late-onset disease, he stated.

Marshall posits that the microbiome is a primary suspect in this shift. He suggested that specific alterations in the microbiome—potentially influenced by factors such as diet or environment—might be concentrated in the distal colon, serving as a catalyst for oncogenesis. Although scientific observation currently outpaces the mechanical explanation for this phenomenon, Marshall compared the current state of research to Darwin’s discovery of natural selection: oncologists are witnessing a clear biological pattern before they fully possess the tools to explain or influence the underlying mechanics.

This rise in cancer among young individuals is not exclusive to the colon, as similar trends are being seen in breast and other gastrointestinal malignancies, Marshall noted. However, the phenomenon is most pronounced in CRC. Marshall concluded that solving the mystery of the microbiome's role in the colon could have significant downstream effects on understanding and treating other young-adult cancers.

To hear more exclusive insights on this alarming trend from Drs Marshall and Lieu, be sure to check out our accompanying feature.