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What is colorectal cancer?

Colorectal cancer (CRC) occurs when genetic mutations and epigenetic alterations in the colon accumulate over the years, causing cancer to form in the colon or rectum.1,2 Similar to other cancers, cancerous tissue in the colon can metastasize and lead to death.2

In the U.S. in 2017, CRC was the third most commonly diagnosed cancer in both men and women and the third leading cause of cancer deaths, with an estimated 140,250 new cases and 50,630 deaths in 2018.3 Worldwide, approximately 1.7 million new cases of CRC are diagnosed each year, resulting in over 800,000 deaths annually.4

CRC develops in stages, starting with a local lesion in the colon, gradually advancing into deeper layers, and eventually spreading to other parts of the body.5 Progression of CRC is categorized in the following stages:

  • Stage 0: limited growth to the inner lining of the colon
  • Stage I: growth advanced to the second or third outer layers of the colon, without spreading to distant sites
  • Stage II: growth advanced to the fourth outer layer, or to the outside of the colon, without spreading to distant sites
  • Stage III: growth advanced to lymph nodes, without spreading to other parts of the body
  • Stage IV: spreading of colon cancer cells to different parts of the body (metastasis)
These are alterations in the chemical structure of DNA that do not alter the DNA sequence itself. Epigenetic alterations can happen due to aging, genetics, and exposure to environmental factors such as diet, exercise, drugs, and chemicals. These alterations can also increase the risk of certain diseases.

What are common symptoms?

Because the earliest stage of CRC is often asymptomatic, early detection usually occurs through screening methods such as colonoscopy and fecal occult blood testing. The main symptoms of CRC can occur at any stage, and include (in order of frequency)6:

  • Abdominal pain
  • Change in bowel habits
  • Rectal bleeding
  • Nausea and vomiting
  • Fatigue
  • Anemia
  • Weight loss

 What are the causes?

Adenomatous polyps are premalignant mucosal masses in the colon and rectum that seem to grow slowly over many years, mainly due to genetic mutations. When these polyps are not detected in time, they can progress to CRC. Regular screening for precancerous polyps is recommended, so the polyps can be removed before their cells become cancerous.1,2

CRC risk factors can be divided into two groups: genetic factors and environmental factors.7

Genetic factors (in order of relevance):

  • Family history of CRC or adenomatous polyps: about 25% of patients with CRC have family members who have been affected by the disease
  • Personal history of adenomatous polyps: an individual with a history of adenomas has an increased risk of developing CRC
  • Inflammatory bowel disease (IBD): patients with IBD are 4 to 20 times more likely to develop CRC
  • Age: more of 90% of cases develop after age 50

Environmental risk factors:

  • A “western style” diet
  • Diabetes
  • Heavy alcohol consumption
  • High consumption of red meats
  • Low intake of fruits and vegetables
  • Low intake of dietary fiber
  • Lack of physical activity
  • Obesity
  • Smoking

How does this topic relate to my microbiome?

An imbalance in the gut microbiome and its resulting low-grade inflammation are associated with CRC development, and also affect the likelihood of developing other gastrointestinal conditions such as IBD and irritable bowel syndrome.1 Some bacteria in the gut have been shown to interfere with a person’s response to chemotherapy treatment.8,9 In a recent meta-analysis, researchers were able to identify specific bacteria associated with CRC, including Fusobacterium, Parvimonas, Clostridium, and Enterobacteriaceae.10

Which diseases/topics are related to colorectal cancer?

Comorbidities of CRC include (in order of frequency)11:

  • Cardiovascular diseases
  • Previous cancers
  • Hypertension
  • Chronic obstructive pulmonary disease
  • Diabetes

How can people take action?

If you’re experiencing any symptoms of CRC, visit your healthcare provider. CRC survival is higher when detected at early stages, and regular CRC screening is the best strategy for early detection. Typical 5-year survival rates are 90% for stage 0; 70% for stages I and II; and 10% for stages III and IV.7 The American Cancer Society recommends regular CRC screening starting at age 45; this screening can either be done by a stool-based test or by a visual physical exam (colonoscopy).12

General recommendations for prevention and detection are12,13:

  • A fiber, fruit, and vegetable-rich diet
  • Healthy weight
  • Low consumption of red and processed meat
  • Low consumption of alcohol
  • No smoking
  • Regular exercise
  • Regular screenings, especially after the age of 45


1. Raskov, H., Burcharth, J., & Pommergaard, H. C. (2017). Linking gut microbiota to colorectal cancer. Journal of Cancer, 8(17), 3378–3395.

2. van Engeland, M., Derks, S., Smits, K. M., Meijer, G. A., & Herman, J. G. (2011). Colorectal cancer epigenetics: Complex simplicity. Journal of Clinical Oncology, 29(10), 1382–1391.

3. American Cancer Society (2018). Cancer Facts & Figures 2018. Atlanta: American Cancer Society; 2018.

4. Fitzmaurice, C., Allen, C., Barber, R. M., Barregard, L., Bhutta, Z. A., Brenner, H., … Naghavi, M. (2017). Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015. JAMA Oncology, 3(4), 524–548.

5. Anderson, J. C., & Robertson, D. J. (2012). Overview of Colorectal Cancer. In B. D. Cash (Ed.), Colorectal Cancer Screening and Computerized Tomographic Colonography: A Comprehensive Overview (p. 195). New York: Springer Science & Business Media.

6. Winawer, S. J., Fletcher, R. H., Miller, L., Godlee, F., Stolar, M. H., Mulrow, C. D., … Mayer, R. J. (1997). Colorectal Cancer Screening: Clinical Guidelines and Rationale The Adenoma-Carcinoma Sequence. Gastroenterology, 112, 594–642.

7. Haggar, F. a, Boushey, R. P., & Ph, D. (2009). Colorectal Cancer Epidemiology : Incidence, Mortality, Survival, and Risk Factors. Clin Colon Rectal Surg, 22(4), 191–197.

8. Guthrie L, Gupta S, Daily J, Kelly L. Human microbiome signatures of differential colorectal cancer drug metabolism. npj Biofilms and Microbiomes. 2017;3(1):27.

9. Tilg H, Adolph TE, Gerner RR, Moschen AR. The Intestinal Microbiota in Colorectal Cancer. Cancer Cell. March 2018:1-11.

10. Sze, M. A. (2018). Leveraging existing 16s rRNA gene surveys to identify reproducible biomarkers in individuals with colorectal tumors. MBio, 9(3), e00630-18.

11. De Marco, M. F., Janssen-Heijnen, M. L., van der Heijden, L. H., & Coebergh, J. W. (2000). Comorbidity and colorectal cancer according to subsite and stage: a population-based study. European Journal of Cancer (Oxford, England : 1990), 36(1), 95–99.

12. Wolf AMD, Fontham ETH, Church TR, Flowers CR, Guerra CE, LaMonte SJ, Etzioni R, McKenna MT, Oeffinger KC, Shih YT, Walter LC, Andrews KS, Brawley OW, Brooks D, Fedewa SA, Manassaram-Baptiste D, Siegel RL, Wender RC, Smith RA.(2018). Colorectal Cancer Screening for Average-Risk Adults: 2018 Guideline Update From the American Cancer Society. CA Cancer J Clin. 2018 Jul;68(4):250-281.

13. Zoratto, F., Rossi, L., Verrico, M., Papa, A., Basso, E., Zullo, A., … Tomao, S. (2014). Focus on genetic and epigenetic events of colorectal cancer pathogenesis: Implications for molecular diagnosis. Tumor Biology, 35(7), 6195–6206.