NEW DELHI — Chronic inflammation may increase the stiffness of the colon, potentially driving the development and progression of early-onset colorectal cancer, according to a new study.
Colorectal cancers that are not linked to genetic syndromes and typically occur after age 50 are known as average-onset or sporadic cases. While the incidence and death rates from these cancers have declined over the past three decades, colorectal cancers diagnosed before age 50 — referred to as early-onset cases — have risen sharply during the same period.
The study, led by researchers from the University of Texas at Dallas and UT Southwestern Medical Center, suggests that changes in the physical properties of colon tissue may play a key role in this troubling trend and could open new avenues for prevention and treatment.
“This is the first study to highlight the key role of biomechanical forces in the pathogenesis of early-onset colorectal cancer,” said Jacopo Ferruzzi, an assistant professor of bioengineering at the University of Texas. “Our observations are consistent across multiple length scales and link connective tissue stiffening to altered biochemical signaling in cancer cells.”
Published in the journal Advanced Science, the research analyzed intestinal tissue from patients who underwent surgery to remove colorectal tumors. The team examined 19 samples from patients with average-onset colorectal cancer and 14 from patients with early-onset disease. Each sample included both cancerous tumors and surrounding noncancerous tissue.
The analysis showed that both tumor tissue and adjacent noncancerous margins were significantly stiffer in early-onset cases compared with average-onset cases. Researchers said this suggests that increased tissue stiffness may occur before early-onset colorectal cancer develops.
To understand the cause of the increased rigidity, the team focused on collagen, a structural protein that becomes more abundant and altered during scarring. They found that collagen in early-onset cancer samples was denser, longer, more mature, and more uniformly aligned than in average-onset samples.
These characteristics point to extensive scarring, which the researchers linked to chronic inflammation.
Further analysis of gene activity revealed higher expression of genes involved in collagen metabolism, blood vessel formation, and inflammation in early-onset colorectal cancer tissue. The findings reinforce the idea that long-term inflammation leads to tissue scarring and stiffness, which may help drive cancer development at a younger age.
Researchers said understanding how biomechanical changes contribute to early-onset colorectal cancer could lead to new strategies for early detection and targeted therapies. (Source: IANS)
