What Is Colorectal Cancer?

Colorectal Cancer, also known as bowel cancer, develops in the colon or the rectum (the large bowel or the large intestine).

Our body is made of trillions of cells. These cells are the basic building blocks of all living things.

Each cell has a special characteristic and it grows and divides in a controlled manner in order for the organism to function properly. Normal cells have the ability to reproduce correctly, stop reproducing when necessary, remain in a specific location, become specialised for specific functions and self-destruct when necessary.

You can compare a cell with driving a car; you need a key and once you turn that key several mechanisms are activated and finally the engine will start. By using the pedals (gas or brake) you will either drive (grow) or stop (no more reproduction).

Cells communicate with other cells through proteins (chemical signals).

These signals help normal cells to know when to reproduce and when to stop reproducing (remember the gas or brake pedal in our car). Cell signals are usually transmitted into a cell by specific proteins.

Cells provide structure for the body, take in nutrients from food, convert those nutrients into energy and carry out specialised functions. Cells also contain the body’s hereditary material and can make copies of themselves.

Cells have many parts each with a different function. The cell’s command centre, let’s say the engine, is called the nucleus. This control centre will send directions to the cell to grow, mature, divide or die.

The nucleus contains chromosomes that houses DNA (deoxyribonucleic acid) the cell’s hereditary material. The structure of DNA is described as a ‘double helix’, a spiral staircase. Within DNA are coded instructions for building new cells and controlling how cells behave and these are called genes.

Genes are instruction manuals in our body. They are molecules in our body that explain the information hidden in our DNA and supervises our bodies to grow in line with that information.

Let’s compare this to a library: you have a bookshelf (nucleus), containing 46 books (chromosomes). In these books sentences (genes) are written with letters (DNA).  Normally these books are tightly packed on the bookshelf. Imagine that by accident (sporadic) the book is damaged (pages are torn, letters are missing, …).

Cancer develops when genes responsible for regulating cell growth and differentiation are altered. Such gene alterations (changes in the books or inside a book) include for example:

• a change in the DNA sequence of a gene (called a mutation)
• a change in the number or breakage of chromosomes (called chromosomal instability)
• a change in the length of specific repeat sequences in the DNA (called micro satellite instability).

It actually takes a number of mutations before a cell becomes cancerous.

Some types of mutation that are linked to cancer are present in all cells. Other mutations are present only in cancer cells. Mutations cause cancer cells to not behave like normal cells and sometimes to look different from normal cells:

• Cancer cells grow more quickly and live longer than normal cells, they don’t die, they form a mass(tumor).
• They can grow into surrounding tissue and even travel to another part of the body and start growing there(metastases)
• Cancer cells send out chemical signals that promote the formation of new blood vessels(angiogenesis)

During previous investigations, your physician will have collected small samples of tissues cells (biopsy) and sent these for testing to a pathologist.

The pathologist will have examined your tissue with a technique called molecular profiling. This technique  reveals a subset of specific genes  (specific pages of the books) expressed in a cell or a tissue. This technique is increasingly being used to determine the profile of genes and gene alterations expressed in cancers.

The molecular profile of your cancer together with the clinical information (e.g. stage of your tumour)  helps doctors to identify the possibility of underlying genetic predisposition of the cancer, its potential to metastasize, its responsiveness to treatment and the likelihood of recurrence.

A number of gene alternations have been described:

• RAS mutations (KRAS, BRAF and NRAS mutation)
• Mismatch repair (MMR) and Micro satellite instability (MSI)

RAS is a family of related proteins that are involved in transmitting signals within cells. Mutation in RAS can lead to the production of permanently activated RAS proteins with overactive signaling inside the cell with ultimately activation of genes involved in cell growth, differentiation and survival.

Mutations of KRAS are most common in colorectal cancers with a frequency of 30–50%, BRAF are 10–20% and NRAS mutations are found in about 3–5%.

The presence or absence of these mutations helps to determine the optimal treatment and whether specific drugs might be effective or not. (see section on treatment)

The biologic function of mismatch repair (MMR) genes is to repair  transcription mistakes that sometimes occur in the DNA when cells divide.

Remember our book, try to envision typing a lengthy but important document on a computer with a broken spell‐check function; for most of us the longer we type the higher the number of spelling errors. In many ways the MMR genes serve as a “spell‐check” protein for DNA. The proteins produced by the MMR genes analyse the DNA looking for any “spelling” errors in the genetic  sequence.  If an error is detected the proteins can remove the faulty segment of DNA and replace it with the correct sequence.

In some colorectal cancers, MMR mutations cause one or more MMR proteins to be absent. DNA errors are not corrected and the number of gene mutations (typos) increases. Doctors call this dMMR (defective mismatch repair).

The DNA errors caused by defective mismatch repair often occur in microsatellites. These are tiny little parts of the DNA code that due to dMMR cause the micro satellites to be shorter or longer. This is called MSI (micro satellite instability).

Testing for loss of MMR proteins or MSI is needed for all people with colorectal or rectal cancer as this may affect your treatment plan.