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When it’s more than bad digestion: colorectal cancer

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Colorectal cancer may be many things, but at least it doesn’t lie with its name. It is a cancer. It occurs in the rectum or colon. The appendix region is also included, but calling it colorectalappendiceal cancer was possibly too long.

Excluding skin cancers, colorectal cancer is the third most common cancer in men and the second most common cancer in women in the world. Contrary to what the previous sentence may suggest, incidence and mortality is higher in men.

Worldwide, more than one million people develop colorectal cancer annually. In 2010 there were 715 000 deaths due to the disease. While in countries where it has been historically common, such as the United States, the incidence has stabilised or even decreased, globally it has increased, and the average age of onset has decreased.

Again, in the US, 106,970 new cases of colon cancer and 46,050 new cases of rectal cancer are expected in 2023. Even with declining incidence, 4% of the US population is expected to develop colorectal cancer at some point in their lives.

Despite these figures, it is a relatively preventable cancer. It has been estimated that half of all cases have lifestyle as a primary risk factor. Among the causes are:

Age. Age as a risk factor for cancer? Are older people more at risk of developing the disease? You leave me… asstonished.

Sex. Not the one you do, but the one you have. Being male increases the incidence of the disease, although the prognosis is the same as in women. More men die than women for the simple reason that they suffer more cases.

Diet. It is logical that if a large part of what you eat ends up passing through the colon and rectum, its composition is important in the development of the pathology. Drinking too much alcohol and too little water are both risk factors. A high intake of processed meats would also be on the list.

Low physical activity. Moving your ass protects the bowel.

Obesity. There is a positive correlation between body fat mass and risk of colorectal cancer.

Smoking. Because it is bad for almost everything.

 Some diseases. The most obvious example is inflammatory bowel diseases.

 Genes.

When it's more than bad digestion: colorectal cancer

Colorectal cancer is not very genetic, but there are genetics.

When we are talking about a disease that requires mutations in DNA to occur, that genetics would be a risk factor should come as no surprise to anyone.

Even so, it does not play as much of a role as in other complex diseases.  Only 5-25% of colorectal cancer cases had a significant genetic risk. Family history should be monitored, because having first-degree relatives with the disease is an important risk factor. However, most mutations occur in a timely and unpredictable manner, and do not come from birth.

There are a number of genetic diseases that are also considered risk factors for cancer. The best known is Lynch syndrome. This syndrome is a genetic condition that is inherited in an autosomal dominant manner and increases the risk of various cancers, the main one being colon cancer. These people have alterations in genes such as MLH1 and/or MSH2, which are involved in DNA repair.

Another common suspect is familial adenomatous polyposis and its variants. These are inherited diseases that usually have an altered APC gene and also have autosomal dominant inheritance.

There is also MUTYH-associated polyposis, an autosomal recessive genetic condition where the problem in the story is the MUTYH gene. It is involved in the repair of oxidative DNA damage.

The risk of cancer with these diseases is so close to 100% that we can take it for granted. A recommended treatment is proctocolectomy, the removal of the ENTIRE COLON AND RECTUM. The less you know about this operation and the postoperative period, the better.

In general, it is considered that in this cancer epigenetic alterations are more frequent than mutations. The dominant epigenetic alterations in this pathology are alterations in the expression of miRNAs, hyper- and hypomethylation and alteration in histones, modification of gene expression, mostly protein coding.

From growth to (sometimes) death

In normal evolution, it starts in the epithelial cells of the tissue, forming polyps. Among the first mutations to emerge, one of the pathways affected tends to be the Wnt/β-catenin signalling pathway, which increases its activity. Other mutations join in.

These initially benign polyps progress to colorectal cancer. One of the problems with this disease is that the previous steps are asymptomatic. And when it does present symptoms, the initial symptoms are variable and non-specific. Therefore, often by the time it is diagnosed, the tumours have already invaded a large part of the intestinal wall and/or have affected the regional lymph nodes.

The classic test for detecting this cancer is colonoscopy. Put bluntly, it is a wire with a camera and other capabilities that is passed through the rectum and upwards. Other methods are the double-contrast barium enema, used to x-ray the colon, or faecal occult blood tests (zero invasive, but less safe).

In 2015, the 5-year survival rate for colorectal cancer was 65%. However, this figure is highly dependent on whether the cancer remains localised or has moved to other regions of the body.

One third of people who are diagnosed with the disease die from it.

Treatment is the classic protocol for all cancers. If it is detected in early stages and is localised, it can be removed by surgery. Sometimes it is initially treated with chemotherapy to reduce its size.

Both chemotherapy and radiotherapy are used in specific circumstances. Some studies and trials are also incorporating immunotherapy treatments. All of this is combined with palliative care.

If you want to test your genes to help keep colorectal cancer from sneaking up on you, you can do so with tellmeGen’s Advanced DNA kit.

 

Carlos Manuel Cuesta

Graduate in Biology. PhD in Biotechnology

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