Understanding your colon: How does colorectal cancer develop?

Understanding your colon: How does colorectal cancer develop?

Colorectal cancer is the most common cancer for both men and women combined in Singapore. At our clinic, many patients ask us about the causes of this cancer and how much it has to do with their family history. 

The answer is complex, with many interacting variables. We’ve prepared this guide to provide some answers.  

The three pathways for the development of colorectal cancer

The interaction of genetic and environmental factors influences our understanding of cancer development. In particular, the role of inflammation as a contributory cause in the Tumour MicroEnvironment (TME) helps us to understand why some cancers respond better to treatment, whereas others have a worse prognosis.

There are three main pathways for the development of colorectal cancer:

1. Conventional, which accounts for 70% of colorectal cancer. This pathway results from an accumulation of genetic damage to the cells lining the large intestine. Tumour suppressor genes are affected, like APC, Kras, p53. These result in the release of cell growth suppression and uncontrolled growth, which are hallmarks of cancer.
2. Serrated, so named because of the shape of the polyps, this cancer develops in 20-30 % of people. This is also called the methylation pathway. mutations, BRAF and Kras mark 2 subtypes. This is important as cancers with Kras mutations do not respond as well to monoclonal antibody therapy (a new type of chemotherapy).
3. Microsatellite instability, in 30% of cases, arises from the dysfunction of DNA mismatch repair genes. These are responsible for fixing DNA defects. Tumours are often on the right side of the colon.

The effect of inflammation on cancer development

1. Chronic inflammation is, as the name suggests, an accumulation of toxic agents that can induce and promote cancer growth in the intestinal cells. Examples are high fat, high meat content, highly processed foods, and reduced stool transit time due to low fibre vegetable intake, which are also rich in antioxidants. Some of the harmful chemicals like nitroso compounds (NOC) used in preservatives, heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PAHs) from high heat are used to cook meats.
2. Tumour induced inflammation. A loss of the intestinal barrier function due to the destruction of cells. This allows bacteria to cross the barrier and activate tumour cells by activating signals in the micro environment.
3. Therapy-induced inflammation. Chemotherapy and radiotherapy can in itself cause the release of signals that suppress anti-tumour activity. These can allow cells to metastasize.

Summary slide showing the transition from genetic changes leading to an early adenoma (polyp). Thereafter a late adenoma that undergoes malignant change to an invasive cancer.

New modality of colorectal cancer screening.

Combining a test that detects microscopic amounts of blood in the stool with anomalous tumour DNA. A threshold of a new phase of screening for cancer.

Get treatment for colorectal cancer at our Singapore clinic

The best way to know if you have colorectal issues or are at risk of developing colorectal cancer is to get a diagnosis from a professional.

At The Colorectal Clinic, our doctors have years of experience treating this issue. We have a range of diagnostic tools and treatments, from colonoscopies to colorectal surgery. Book an appointment with us today.