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A new study conducted by researchers from the University of Texas at Dallas and UT Southwestern Medical Centre has found that increased stiffness of the colon, driven largely by chronic inflammation and tissue scarring, may raise the risk of developing early-onset colorectal cancer (CRC).
Colorectal cancers that occur after the age of 50 and are not linked to inherited genetic syndromes are known as average-onset or sporadic CRCs. Encouragingly, both the incidence and mortality of these cancers have declined steadily over the past three decades, largely due to improved screening, early detection, and treatment. In stark contrast, early-onset colorectal cancers (those diagnosed before age 50) have risen sharply during the same period, even as screening programmes expanded for older adults.
This shift is particularly concerning given the global burden of colorectal cancer. According to the World Health Organisation (WHO), colorectal cancer is the second leading cause of cancer-related deaths worldwide. In 2020 alone, an estimated 19 lakh new cases and more than 9.3 lakh deaths were recorded globally. Against this backdrop, the findings of the current study could open new avenues for prevention, earlier detection, and more targeted treatment of this deadly subset of colorectal cancer.
What is colorectal cancer, and how is it caused?
Colorectal cancer is a type of malignancy that develops in the colon (large intestine) or the rectum, which together form the final part of the digestive tract. It is among the most common cancers worldwide and can be life-threatening if not detected and treated early.
Age remains the strongest risk factor for colorectal cancer, with most cases traditionally occurring in people over the age of 50. However, the rising incidence among younger adults suggests that additional biological, environmental, and lifestyle factors are at play.
Several factors are known to increase the risk of colorectal cancer. These include a family history of the disease or inherited genetic conditions such as Lynch syndrome and familial adenomatous polyposis (FAP). Individuals who have previously had colorectal cancer or certain types of precancerous polyps are also at higher risk. Lifestyle factors play a significant role as well. Diets high in processed and red meats and low in fruits, vegetables, and fibre, physical inactivity, obesity, smoking, and excessive alcohol consumption have all been linked to increased CRC risk.
One of the major challenges with colorectal cancer is that it often develops silently. Early-stage disease may cause no noticeable symptoms, making regular screening critical. When symptoms do appear, they can include persistent changes in bowel habits such as diarrhoea or constipation, blood in the stool, abdominal pain or bloating, unexplained weight loss, chronic fatigue, and iron-deficiency anaemia caused by slow internal bleeding.
Findings of the study
The new study, published in the journal Advanced Science, comprehensively links biomechanical changes in colon tissue to the development of early-onset colorectal cancer.
“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 signalling in cancer cells.”
To arrive at these conclusions, researchers analysed intestinal tissue obtained from patients who had undergone surgery to remove colorectal tumours. The study examined 19 tissue samples from patients with average-onset CRC and 14 samples from patients with early-onset CRC. Importantly, each sample included not only the cancerous tumour but also adjacent noncancerous tissue, allowing for detailed comparisons.
Biomechanical testing revealed that both the tumours and the surrounding noncancerous tissue were significantly stiffer in patients with early-onset CRC than in those with average-onset disease. This finding suggests that increased tissue stiffness may not simply be a consequence of cancer, but could precede and contribute to cancer development in younger individuals.
To understand why the tissue was stiffer, the researchers examined collagen, a structural protein that becomes more abundant and altered during scarring and chronic inflammation. They found that collagen in early-onset CRC samples was denser, longer, more mature, and more highly aligned than in average-onset samples. These characteristics point to extensive fibrotic or scar-like remodelling of the colon tissue.
Further genetic analysis strengthened this link. When researchers compared gene activity between the two groups, early-onset CRC tissues showed significantly higher expression of genes involved in collagen metabolism, blood vessel formation, and inflammation.
However, the authors also clearly outlined the limitations of their work. The study had a relatively small sample size, consisting of 19 average-onset and 14 early-onset CRC tissue pairs, and not all samples yielded complete biomechanical data due to tissue damage or insufficient size. The researchers noted a lack of rectal cancer samples in the average-onset group, likely because aggressive chemoradiation therapy reduces tumour size and limits tissue availability for research.
They also acknowledged that colorectal tissue exhibits highly anisotropic properties, meaning it behaves differently depending on the direction of force applied. Due to limited tissue availability, the team was unable to explore multiaxial mechanical behaviour and instead relied on models assuming isotropic properties. Spatial transcriptomic analysis was conducted on a limited number of regions and was not consistently performed on both normal and cancer tissues in all cases. Additionally, the “matched normal” tissues were taken from areas adjacent to tumours, which may be influenced by field effects.
Despite these constraints, the study stated that “a coherent mechanobiological framework emerges from our multiscale approach integrating biomechanical measurements, quantitative histology, cellular phenotype analysis, spatial transcriptomics, and in vitro modelling.” They concluded that pro-inflammatory and pro-fibrotic remodelling drives tissue stiffening, leading to increased epithelial YAP activity and cell proliferation (key processes in early-onset CRC development).
The researchers emphasised that future studies should focus on understanding biochemical and biomechanical interactions between stromal and epithelial cells, systematically manipulating tissue stiffness to define its role in cancer behaviour, and identifying mechanical biomarkers that could serve as early predictors of disease.
Significance for India
The findings are particularly relevant for India, where colorectal cancer is emerging as a growing public health concern. According to the World Cancer Research Fund, India recorded 70,038 new colorectal cancer cases in 2022, with an age-standardised incidence rate of 4.9 per 100,000 (which means that roughly five out of every one lakh people developed colorectal cancer, after accounting for differences in age distribution)
Out of approximately 1.92 million global cases, India ranked fifth after China, the United States, Japan, and Russia.
Concerns about younger patients are not new in the Indian context. A 2017 study conducted at a tertiary cancer centre in India examined 778 colorectal cancer patients registered between August 2013 and July 2014. The study compared patients aged 45 years or younger with those older than 45 and followed them for a median period of nearly 28 months.
The researchers found that younger patients more commonly presented with poor tumour differentiation, node-positive disease, and rectal cancers. They also received more intensive neoadjuvant treatments. While there was no significant difference in overall survival between the two age groups, disease-free survival was significantly lower among younger patients. “This study confirms the high incidence rates of CRC in young Indian patients,” the authors noted, adding that longer follow-up would be required to assess survival differences more clearly.
More recent research has added nuance to this picture. A 2024 hospital-based study from eastern India examined the clinico-demographic profile of young colorectal cancer patients and analysed trends over time at a major tertiary cancer centre in Bihar. The retrospective observational study, conducted at the State Cancer Institute, Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, included 1,028 histopathologically confirmed CRC cases, of which 344 patients (33.4 per cent) were younger than 40 years.
The study found that the median age among young CRC patients was just 30 years, with cases ranging from 12 to 39 years. Rectal cancer was the dominant subsite, affecting nearly three out of every four young patients, and Stage III disease was the most common stage at diagnosis.
Chemotherapy was the most frequently administered treatment.
Crucially, while the proportion of young CRC patients was significantly higher than that reported in developed countries, the study found no statistically significant increase over time. “The trends of this proportion have been consistent over the study period, i.e., from 2014 to 2021, without any significant change in our hospital-based cancer registry.
Rectal cancer affected nearly three out of every four CRC patients in this age group. More advanced disease at presentation emphasises the need for measures of screening, early diagnosis, and adequate infrastructure for treatment,” the study concluded, suggesting that the challenge in India may lie less in a rapidly rising incidence among the young and more in delayed detection, site-specific disease patterns, and gaps in early diagnostic pathways.
According to a recent Lok Sabha reply, under the National Programme for Prevention and Control of Non-Communicable Diseases (NP-NCD) within the National Health Mission, the government supports screening, early diagnosis, referral, treatment, and health promotion for cancers. As of recent data, 770 District NCD Clinics, 364 District Day Care Cancer Centres, and over 6,400 NCD clinics at Community Health Centres have been established nationwide.
Advanced care is provided through 19 State Cancer Institutes and 20 Tertiary Cancer Care Centres, with diagnostic and treatment facilities approved across all new AIIMS institutions. Specialised facilities such as the National Cancer Institute in Jhajjar and the Chittaranjan National Cancer Institute in Kolkata offer superspecialty care, while additional cancer centres have been set up under the Department of Atomic Energy. The Union Budget 2025–26 further approved more than 200 new Day Care Cancer Centres across the country.
This story is done in collaboration with First Check, which is the health journalism vertical of DataLEADS.
