What is colon cancer ?

Colon and rectal cancers (colorectal cancers or CRC) are malignant tumors that develop from the cells lining the colon (large intestine) and rectum.

These cancers affect the colon in 60% of cases and the rectum in 40% of cases.

Colon and rectum

The colon measures approximately 1.50 meters in length. It follows the small intestine, which has an average length of 6 meters (duodenum followed by the jejunum and then the ileum). The colon is located in the abdominal cavity, anterior to the loops of the small intestine.

It is divided into five segments :

  • The cecum, which joins the end of the small intestine ;
  • The ascending colon or right colon, which ascends to the liver to form an angle called the right colic angle ;
  • The transverse colon, which extends from the right colic angle to the left colic angle ;
  • The descending colon or left colon, which descends from the left colic angle and ends at the sigmoid colon ;
  • The sigmoid colon, which forms an S shape and joins with the rectum.

The rectum measures approximately 8 cm in length. It follows the sigmoid colon and ends at the anus.

After food digestion by the stomach and small intestine, the colon's role is to concentrate fecal matter by reabsorbing water and salt.

The colon contains a significant microbial flora (microbiome), composed of 38,000 billion bacteria.

By comparison, our body is composed of 38,000 billion cells. This microbiome plays a crucial role, particularly in the formation and development of metastases or in the response to treatments for many cancers.

Polyps

A polyp is a small growth that develops in the body's natural cavities (intestines, uterus, bladder, larynx).

It can evolve into an adenoma, a benign tumor that can sometimes transform into cancer.

Polyps in the colon and rectum are common, present in 20 to 50% of individuals. Their size can vary from a few millimeters to several centimeters. When there are numerous polyps in an individual (>10), it is referred to as polyposis.

Expert perspective

Only 5% of polyps become cancerous during a person's lifetime.

When this happens, it typically takes 10 to 15 years for a polyp to transform into cancer .

This transformation, called carcinogenesis , occurs through two different pathways: the first pathway, due to chromosomal instability, is the most common and affects 85% of sporadic colorectal cancers, which do not have a hereditary familial component.

This pathway mainly affects the left colon.

Chromosomes and chromosomal instability

Chromosomes are structures found in each nucleus of the 30,000 billion cells in our body.

Each human cell has 23 pairs of chromosomes that appear as visible rods under a microscope during cell division. Half of the chromosomes come from the father and the other half from the mother.

Chromosomes are made up of proteins and DNA. DNA itself consists of a sequence of four different elements named A, T, G, or C, according to the first letter of their full name.

DNA forms double helix strands. If all the DNA strands contained in the 46 chromosomes were laid end to end, the total length of DNA in a cell would be nearly 2 meters. Chromosomes and their DNA contain all the information necessary for the functioning of each cell.

In cases of chromosomal instability, there is a gain, loss, or rearrangement of chromosomes. This instability can contribute to the transformation of a normal cell into a cancerous cell.

The second pathway of carcinogenesis is due to genetic instability, affecting 15% of colorectal cancers. It primarily affects the right colon and can occur sporadically in an individual (sporadic origin) or be of hereditary origin.

💡 DID YOU KNOW ?

Genes are small segments of DNA located on our chromosomes within the nucleus of each of our cells. These genes guide the production of proteins, essential elements for cell functioning. Each cell contains approximately 21,000 genes.

Mutations can occur within genes, changing one element to another within one or more genes. These mutations can be inherited from a parent to a child ( inherited genetic mutations ) or occur spontaneously in an individual during their lifetime ( sporadic mutations ). Some mutations can increase the risk of developing cancers. Cells in colorectal cancer have at least 15 mutated genes.

When cells divide, the DNA of the daughter cells must be identical to that of the mother cell. However, errors can occur during this division. Normal cells have a system to repair these errors ( Mismatch Repair system or MMR ).

This system operates through 4 important proteins : MLH1, PMS2, MSH2, and MSH6 . Sometimes, one of these proteins is deficient, causing the cell to be unable to repair DNA ( Mismatch Repair Deficiency or MMR-D ). This deficiency can be sporadic or inherited. It leads to multiple mutations, and cells are said to have genetic instability. These mutations occur particularly in highly repetitive DNA sequences called microsatellites. Cells with multiple mutations in microsatellites are said to have microsatellite instability (MSI).

These mutations contribute to a stronger stimulation of the immune system. Therefore, patients with tumors that have a deficiency in the repair system (MMR-D tumors) and microsatellite instability (MSI tumors) may benefit from immunotherapy treatment (discussed further below). Conversely, patients with tumors that have a functional repair system (MMR-proficient tumors) and no microsatellite instability (Microsatellite Stable or MSS tumors) respond less to immunotherapy.

Hence, it is important to determine whether a tumor has a deficiency in the repair system and genetic instability leading to microsatellite instability, or in other words, it is important to determine the MSI status of a tumor.

At the beginning of its progression, colorectal cancer remains confined to the inner wall of the colon or rectum and does not spread to other organs (non-invasive stage or stage in situ cancer). It takes 5 to 10 years from the presence of the first cancer cells to the discovery of a tumor measuring 0.5 to 1.5 centimeters.

This tumor is already composed of approximately one billion cancer cells.

If left untreated, an in situ colorectal cancer can gradually infiltrate the walls of the colon or rectum to invade surrounding tissues and adjacent organs (invasive stage cancer). The cancer cells will invade nearby lymph nodes. They will also invade the peritoneum, the membrane that covers the abdominal cavity and the viscera it contains. Tumor cells can form distant metastases in the liver (75% of metastasis cases), lungs (15% of cases), or more rarely in the bones or brain (5% of cases).

Today, these cancers can be diagnosed early through organized screening. In the initial stages, the disease can be treated more easily and often cured.

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Article updated on Nov 14, 2024

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