Colorectal Cancer and the Two-Hit Hypothesis

Written By Emily Miller

We’ve all seen it on the internet by now: “Colorectal cancer is increasing in individuals under the age of 50!” Whether it’s environmental, diet, genetics, or a combination of the three, the fact remains – people are getting colon cancer younger than ever. 

One of the biggest red flags that a cancer diagnosis may have a genetic or hereditary component is being diagnosed under the age of 50. As our bodies age, our cells lose some of their ability to fight off diseases like cancer, so we expect these diseases to increase in frequency as someone gets older. But, when someone has a genetic predisposition to developing cancer, it’s easier for a sporadic change (suddenly, by chance) to result in the uncontained cell growth that results in a tumor developing. 

Think of your genes as spelled out of individual letters, where a change in one of those letters may affect the ability of the gene to function properly. Some changes are germline changes, which means they are present from birth and are in every cell of the body. Others are called somatic changes, meaning they only occur in some cells and may occur at any point in time due to errors in cell division, DNA replication, or other issues. Everyone has two copies of each gene. If one copy of the gene has a permanent change in the spelling that means it can’t function properly when it needs to, it’s vulnerable to a second change happening randomly in a newly formed cell, which then means both copies of the gene aren’t working as they should. The new cell has the germline change (all cells have this change) and the somatic change – and suddenly this cell can’t function properly. This is known as the two-hit hypothesis. 

This inability of the cell to function properly can result in cancer in different ways depending on the function of the gene that is no longer doing its job properly. Some genes protect the body from cancer by stopping cell growth at a certain point to control it. Others are responsible for DNA repair, and cancer occurs when mistakes in DNA replication occur. Finally, some genes result in uncontrolled cell growth when they are turned “on,” causing cancer. 

So, what are some other red flags that a diagnosis of colon cancer might be hereditary? The following signs in your personal or family history may indicate that genetic counseling and testing might be useful: 

  • You or a family member had colon or rectal cancer before age 50.

  • Two or more close relatives (parents, siblings, children, grandparents, aunts, uncles) have had any of these: colon/rectal, uterine (endometrial), ovarian, prostate, brain, bladder, kidney, or ureter cancer.

  • Any of those cancers were diagnosed in a close relative before age 50.

  • Three or more family members on the same side of the family have had any of those cancers, at any age.

  • Your or your relative’s cancer has unusual features, like multiple tumors or specific genetic changes found in pathology.

Of course, sometimes cancer isn’t hereditary, and there are other risk factors that may increase the chances of developing colon cancer. These include: 

  • Low fiber, high-fat diet

  • Lack of exercise

  • Smoking and tobacco use

  • Obesity

  • Diets high in processed foods/meats

  • Environmental factors

Some ways to decrease your risk of developing colon cancer, or any cancer, include: 

  • Eat lots of fruits and vegetables

  • Supplement your fiber intake

  • Exercise regularly

  • Quit smoking

  • Don’t drink alcohol, or drink it sparingly

  • Maintain a healthy weight

  • Get routine screenings for your age group

Routine screenings for colon cancer are critical; colonoscopies are recommended for anyone age 45 and older. If you have a family history of colon cancer, you should get one at age 40, or beginning 10 years before the age at which your family member was diagnosed. 

Curious about whether genetic testing for colon cancer could be right for you and your family? See yourself in the list of red flags we shared? Living Roots Genetics can help. Check out the rest of our website to learn more about our services and how genetic counseling can help you on your health journey.

Emily Miller