Colon Cancer: Symptoms and Treatment

Introduction

Colon cancer is a type of cancer that develops from the colon (part of the large intestine). The colon is the final part of the digestive tract. Although colon cancer typically affects older adults, it can occur at any age. It usually begins as benign (non- cancerous), small clumps of cells called polyps that form on the inside of the colon. These polyps are harmless at the beginning, but overtime some could become malignant (cancerous).

Also, these polyps might be small and produce few or no symptoms at all. Due to this reason, most doctors are recommending regular screening tests, such as colonoscopy or sigmoidoscopy to help improve the prevention of colon cancer by identifying and removing these polyps early on before they turn into malignant cancer since most of them are benign in the beginning. During a colonoscopy, small polyps may be removed if detected. However, if a large polyp or tumor is found, a biopsy is performed in order to check if it’s malignant or benign.

These tests are then followed by medical imaging to determine if the cancer has been spread or not. Screening is usually recommended starting from the age of 50. Colon cancer is sometimes referred to as colorectal cancer or CRC, which is a term that combines rectal cancer and colon cancer, which starts in the rectum (Creagan, Giridhar, 2020).

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Signs and Symptoms

As symptoms develop, they may vary depending on the size of the tumor and location in the large intestine. Symptoms that come early may only affect colon and result in changes in bowel habits. With the growth of the cancer there could also be systematic symptoms that affect not only the colon but the whole body, such as jaundice and swelling. Colon cancer signs and symptoms may include:

• Frequency changes in bowel movement
• Loose or watery stools
• Unfamiliar abdominal pain, including bloating and cramps
• A feeling that you can’t empty your bowel completely
• Constipation
• Bloody stool
• Bleeding from the rectum
• Fatigue or weakness
• Unintentional weight loss
• Anemia (Due to blood loss)
  (Creagan, Giridhar, 2020)

Disease from genetic perspective

Colon cancer is suspected to arise via two different types of pre-cursor polyps in two distinct pathways: conventional adenomas by the conventional adenoma-to-carcinoma sequence and serrated adenomas according to the serrated adenoma-to-carcinoma theory. Although the conventional adenomas arise from mutation of the gene known as APC, colon cancer progression is a gradual process.

The job of the APC gene is to prevent accumulation of β-catenin protein, without APC the β-catenin accumulates to higher levels than usual and moves into the nucleus, binds to DNA, and activates transcription of proto-oncogenes (Cappell, 2008). These genes are usually important for the regeneration and differentiation of steam cells, but when inappropriately made at higher levels than usual, they could cause cancer. In most colon cancer cases APC gene is mutated, but some cancers have increased levels of β-catenin, due to mutations of β-catenin protein (CTNNB1) that block the breakdown of itself, or have mutations in other genes with its function being similar to APC such as the following: AXIN1, AXIN2, TCF7L2, or NKD1 (Markowitz, Bertagnolli, 2009).

Also, the genetic defect of serrated adenomas is unknown. Most cases of colorectal cancer are sporadic in nature and only few are hereditary. Hereditary forms of colorectal cancer such as Lynch syndrome are caused by a mutation in one of the DNA mismatch repair genes, which include MLH1, MSH2, MSH6, PMS2, and EPCAM. Mutations in these genes inhibit the ability for proper mismatch repair during replication, causing an accumulation of DNA mutations which leads to microsatellite instability. Lifestyle factors influencing the risk of colorectal cancer include smoking, alcohol consumption and increased body weight (McKenzie, 2018).

Basic and clinical research efforts in colorectal cancer began in the 1980’s and continue to accumulate new information. Great studies have been made in order to understand the pathogenesis. Epidemiologic studies have contributed to our understanding of the role diet may play in this disease. Adenomatous polyps and adenocarcinoma are epithelial tumors of the large intestine and the most common and clinically significant of intestinal neoplasms.

The potential for polyps or adenomas to develop into cancer increases with patient age. Adenomas greater than 1 cm, with extensive villous patterns are at increased risk of developing into carcinomas. The development of cancer of the colon and rectum is thought to be influenced by diet, genetic, and environmental factors. The prevalence of colorectal cancer begins to increase at age of 40 but remains relatively low until the age of 50 and then rapidly increases again. This prevalence appears to double at about age 80.

Those with a individual history of adenomas are at increased risk. Individuals with a family history of colorectal cancer or adenomas, various genetic polyposis and nonpolyposis syndromes, other types of cancers, and inflammatory bowel disease are at higher risk of developing colorectal cancer. However, it’s important to note, that most patients have no identifiable genetic risk factors. (Hopkins Medicine, 2013)

Treatment from genetic perspective

Treatment of metastatic colon cancer is guided majorly by molecular testing of the tumor. The American Society of Clinical Oncology (ASCO) has issued evidence-based guidelines on colon cancer molecular testing. Among the recommendations are below:
RAS mutational testing of colon carcinoma tissue should be performed for patients who are being considered for anti-EGFR therapy.
BRAF V600 mutational analysis should be done with deficient mismatch repair (dMMR).
dMMR testing must be performed in all colon cancer cases for prognostic classification and to identify all Lynch syndrome patients.
Formalin-fixed, paraffin-embedded tissue is an acceptable specimen; other specimen will require more validation.
(Dragovich, 2020)

Conclusion

Modulation of nutritional choices affects the incidence of colon cancer to a high extent. The main nutritional factors that increase the risk of this disease include high red meat intake, calcium, vitamin D, folic acid, alcohol, fiber, phytonutrients and dietary fatty acids. Most colorectal cancer patients are diagnosed when symptoms have already begun to show. If diagnosed while asymptomatic, the disease is most likely in its early stages. Fecal occult blood is the most common screening procedure leading to diagnosis in people with no symptoms. (Treyzon, Heber, 2006)

Sources

1. Dragovich, T, 2020, “Colon Cancer Workup, 2020”, Medscape, available at:( https://emedicine.medscape.com/article/277496-workup) (Accessed at:05-05-2020)
2. Markowitz, S., Bertagnoli, M., 2009 “Molecular Basis of Colorectal Cancer”, The National Center for Biotechnology Information (NCBI), Available at: (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843693/) (Accessed:28-05-2020)
3. McKenzie, S., 2018, “Colorectal Cancer Pathogenesis”, Available at:( https://www.news-medical.net/health/Colorectal-Cancer-Pathogenesis.aspx) (Accessed:27-05-2020)
4. Hopkins Medicine, 2013, “Sporadic Nonhereditary Colorectal Cancer”, Available at: (https://www.hopkinsmedicine.org/gastroenterology_hepatology/_pdfs/small_large_intestine/sporadic_nonhereditary_colorectal_cancer.pdf) (Accessed:27-05-2020)
5. Treyzon, L, Heber, D, 2006 “Nutritional Oncology (Second Edition), 2006”, Available at: (https://www.sciencedirect.com/topics/medicine-and-dentistry/colon-cancer) Accessed at (10-06-2020)