Colorectal Cancer Risk Factors: Part 1

Part 1: The things you cannot change. 

You don’t think you’re at risk? How do you know?  

Let’s talk about risk factors for developing colorectal cancer. Generally, there are two categories of risk factors, those you cannot change and those you can.

We are going to start off with the risk factors that you cannot change. 

Your age. Sorry, there is no magic rewind button. The older you get, the more your risk increases. This is the case for many cancers. Most cancers are diseases of age.

Your family history. You can’t pick your family. If colorectal cancer runs in your family, you are at increased risk of getting it yourself. Your risk level is affected by the following factors:  

(Not to complicate matters, but even your family history risk will change over time.)

Your genomics. You can’t change how you were built. Your genomics are basically the instruction manual for your body. It’s a long book - over 6 Billion letters. Amongst those letters (represented by A, T, C or G in unique order), are little “markers.” These markers are just a change in a letter; in some people it may be an A, in others a G. There are thousands of these little differences between people. With the right bioinformatic tools, we can compare these little differences and ask what they might indicate. In the case of colorectal cancer, we have found a handful of these differences that are associated with the incidence of the disease. This is what we call polygenic risk.

Another type of genomic risk that is much rarer can cause a hereditary genetic cancer syndrome. They too are caused by changes in the DNA, but unlike the ones mentioned above, this change is not just one of many “markers” of risk. Instead, it is a single change that directly impacts the function of a gene. Basically, the gene “breaks.” Luckily everyone has two copies of a gene—a back-up (like keeping a spare tire in your car). But, this is why people with hereditary cancer syndromes, like Lynch Syndrome for example, have a higher risk of developing cancer, they are missing the “back-up” copy. Back to the car analogy—if that person gets a flat tire, they are now driving on their rim—slowly causing more and more damage. Not only will the risk for developing colorectal cancer be higher for this person, but the chance of developing it earlier in life is more likely as well.

And finally, the last genomic risk we will mention is called epigenetic risk. This type of risk includes changes that can happen over time as you age, as a result of your environmental exposure. A well-known example of an “environmental exposure” is smoking. Smoking can change methylation patterns in your DNA. ¹ Without going into any detail, methylation is just one type of epigenetic event, but having more (or less) methylation can change the function of your genes by signaling your body to be less (or more) active in making a gene product (in a process known as transcription). There is suggestion that these types of epigenetic changes may occur in the womb, before birth, or even may be passed down from parent to child. 

Your ethnicity/race. This is a tricky one. There is clearly increased risk of developing colorectal cancer for African American, Japanese American and Native Hawaiian men and women. ² However, there is a lot of evidence suggesting the “US environmental factors” like diet, obesity rates, smoking, and lack of exercise may be impacting people’s risk. For example, US-born Japanese men were twice as likely to develop colorectal cancer compared to foreign-born Japanese men. ³  Similar data can be observed across many different ethnicities and races inside the US versus outside the US. However, globally, there does appear to be a trend in increasing colorectal cancer incidence, even in countries where the levels used to be low, which may be due to evolving environmental and lifestyle practices. ⁴  More investigation needs to be done to better understand the differences in colorectal cancer incidence between ethnicities/races and how the environmental impacts including diet and lifestyle habits interact with known genetic markers of risk. And finally, in the US, our socioeconomic inequities amplify some of these environmental risk factors that may be contributing to increased incidence. Until we better understand all of these risks, your doctor may recommend earlier screening based solely on your race or ethnicity.

Your health conditions. Diseases like diabetes and inflammatory bowel disease (Crohn’s and Ulcerative Colitis) increase your risk of colorectal cancer. You should be screened earlier than the average adult.

There are a lot of risk factors that you may have no control over. Stick with us to read part 2 of this blog series to understand the factors that you can control. There is a lot you can do to be proactive about your colorectal health.

Sources

¹ Barrow TM, Klett H, Toth R, Böhm J, Gigic B, Habermann N, Scherer D, Schrotz-King P, Skender S, Abbenhardt-Martin C, Zielske L, Schneider M, Ulrich A, Schirmacher P, Herpel E, Brenner H, Busch H, Boerries M, Ulrich CM, Michels KB. Smoking is associated with hypermethylation of the APC 1A promoter in colorectal cancer: the ColoCare Study. J Pathol. 2017 Nov;243(3):366-375. 

² Ollberding NJ, Nomura AM, Wilkens LR, Henderson BE, Kolonel LN. Racial/ethnic differences in colorectal cancer risk: the multiethnic cohort study. Int J Cancer. 2011;129(8):1899-1906. 

³ Flood DM, Weiss NS, Cook LS, Emerson JC, Schwartz SM, Potter JD. Colorectal cancer incidence in Asian migrants to the United States and their descendants. Cancer Causes Control. 2000 May;11(5):403-11. 

⁴ May FP, Anandasabapathy S. Colon cancer in Africa: Primetime for screening? Gastrointest Endosc. 2019 Jun;89(6):1238-1240. doi: 10.1016/j.gie.2019.04.206. PMID: 31104752.