Colorectal Adenocarcinoma

Colorectal adenocarcinoma is the most common type of cancer in the large intestine and colon, it accounts for 15% of cancer related deaths in the United States (1) and second most common cause of cancer related death in Ontario. (2)

Epidemiology

Mostly affects individuals between 60 to 70 years old. Only 20% of cases occur before 50. (1)
Affect males and females equally. (1)
Common in the United States, Canada, Australia, and New Zeland. (1)

Risk Factors

Diet high in refined carbohydrates and fats. (2)
Diet lacks unabsorable (insoluble in water) fibers. (2)
Lack of micronutrients like Vitamin A, C, and E. (1)
Adenomatous polyps. (1)
Smoking and alcohol. (2)
Genetic factors. (2)

Signs & Symptoms

Blood in the stool. (2)
Change in bowel habit (diarrhea or constipation). (2,3)
Abdominal discomfort such as cramps. (3)
Unintentional weight loss. (3)
Iron deficiency anemia. (2)

Usually asymptomatic at first. Diagnosis starts with detection of blood in feces through fecal immunochemical test as bleeding can be occult. If positive, further tests such as barium enema, sigmoidscopy, and colonoscopy are used for confirmation. (1,2)

Pathogenesis

Usually arise from adenomatous polyps. (1)
Diet may alter the activity of gut microbiota to produce potential carcinogens. (1)
Acquirements of genetic mutations. (1,2)

Common mutations leading to colorectal adenocarcinoma:

Loss of function of adenomatous polyposis coli (APC) on 5q21 is seen in 80% of cases. APC regulates the oncogene beta-catenin. Overexpressed beta-catenin can stimulate other oncogenes such as MYC and cyclin-D1. (1,2)
hMSH2, hMLH1, hPMS1, and hPMS2 are mismatch repair genes. Loss of them leads to microsatellite instability.
Gain of function of K-ras, which is an oncogene involved in intracellular signalling. (1)

Treatment & Prognosis

Stages of colorectal adenocarcinoma (4):

Stage 0: Tumor is only in the mucosa.
Stage 1: Invasion into the wall of the colon but muscularis propria is not affected yet.
Stage 2: Further spread into or penetrate the wall of the colon but not lymph nodes yet.
Stage 3: Tumor spread to lymph nodes.
Stage 4: Metastasis of tumor to other organs, such as liver, lungs, or ovaries.

Surgical resection is curable if caught in early stage. (2)
Chemotherapy and radiation can be applied as well. (2)
Metastasis occurs through lymphatic system to lymph nodes or portal venous system to liver (most common). (2)
Survival rate depends on the staging. Could be as low as 17% if metastasized to distant organs. (4)