Study shows a stiffer colon may raise the risk of early-onset colorectal cancer

New Delhi: Chronic inflammation is likely to increase the stiffness of the colon, which may in turn increase the development and progression of early-onset colorectal cancer (CRC), according to a study.

CRCs that are not caused by genetic syndromes and that occur at an average age of over 50 are known as average-onset or sporadic CRCs. The incidence and deaths from average-onset CRC have decreased over the last three decades.

At the same time, the incidence and deaths from CRCs that occur before age 50, known as early-onset CRCs, have risen dramatically during the same period.

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The study led by researchers from the University of Texas – Dallas and Southwestern Medical Centre could lead to new ways to prevent and treat this deadly subset of CRC.

“This is the first study to highlight the key role of biomechanical forces in the pathogenesis of early-onset CRC,” said Jacopo Ferruzzi, 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.”

For the study, published in the journal Advanced Science, the researchers worked with intestinal tissue from patients who underwent surgery to remove their cancerous tumors. They took 19 samples from patients with average-onset CRC and 14 from patients with early-onset CRC. Each sample included not only malignant tumours but also their noncancerous margins.

Tests showed that both the tumours and the noncancerous tissue were significantly stiffer in samples from patients with early-onset CRC compared with those from patients with average-onset CRC. These findings suggest that an increase in stiffness may have preceded early-onset CRC development.

Searching for reasons behind this increased rigidity, the research team examined collagen — a protein that increases in abundance and changes conformation with scarring in both sample types.

They found that collagen in the early-onset samples was denser, longer, more mature, and more aligned than that in the average-onset samples.

Those factors underscore the role of scarring in early-onset CRC tissue.

Further, when scientists compared gene activity in the two sample types, they saw a significant increase in the expression of genes associated with collagen metabolism, blood vessel formation, and inflammation in the early-onset CRC tissues, further reinforcing that scarring from chronic inflammation is responsible for tissue stiffness.