The Catch Guide to Colorectal Cancer

Overview of Colorectal Cancer

Colorectal cancer^[1] originates in the colon or rectum, portions of the large intestine. It develops from abnormal growths in the colon lining (polyps) that can become cancerous over time. Colorectal cancer is one of the most common cancers worldwide, and incidence has steadily risen in younger individuals in recent years. While there are several hypotheses for the sharp increase in early onset colorectal cancer, there is no definitive explanation. 

Colorectal cancer frequently does not cause any symptoms, particularly at early stages, which is why it is incredibly important to get screened. 

At later stages, symptoms of colorectal cancer can include: 

• Changes in bowel habits that last longer than a few days (such as diarrhea or constipation)
• Narrowing of the stool that persists
• Stomach pain
• An urge to defecate that is not relieved by defecation
• Black or tar-colored stools
• Bright red blood in the stool from rectal bleeding
• Abdominal pain
• Weakness
• Fatigue
• Unintended weight loss

These symptoms may be caused by any number of health conditions, and should be evaluated by a medical professional. 

Some of these symptoms may be the result of anemia caused by loss of blood; low red blood cell counts (anemia) may be an early sign of colorectal cancer. If the cancer spreads, it may additionally cause jaundice, enlargement of the liver, or difficulty breathing. Any of these symptoms may be caused by multiple different conditions, and should be evaluated by a medical professional.

Colorectal cancer almost always presents as an adenocarcinoma, which begins in the cells that make the mucus that lubricates the colon and rectum. The specific subtype of adenocarcinoma may impact your prognosis, and is something you should discuss with your doctor. 

There are also less common varieties of colorectal cancer, each characterized by distinct features and biological behaviors: 

• Gastrointestinal stromal tumors (GISTs): These cancers form in the nerve cells in the gastrointestinal tract. These tumors are more likely to form in the small intestine or stomach, and may be benign, but can occasionally form in the colon or rectum. 
• Carcinoid tumors: Carcinoid tumors^[2] originate in hormone-making cells within the intestine. Neuroendocrine tumors such as these are usually slow-growing, though they can occasionally be more aggressive. 

Survival Rates and Incidence

Colorectal cancer survival rates are  based on how far the cancer has spread:^[3] 

• Localized: There is no sign that the cancer has spread beyond the colon or rectum
• Regional: The cancer has spread outside the colon or rectum to nearby structures or lymph nodes
• Distant: The cancer has spread to distant parts of the body, such as the liver, lungs, or distant lymph nodes

The 5-year survival rate at each stage is shown below:

Below is the overall incidence of colorectal cancer by age group for each gender: 

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Men have a higher incidence of colorectal cancer than women, both overall and across almost all age groups. The incidence of early onset colorectal cancer has been steadily rising for the past several decades, increasing by about 2% per year since 1998. 

Although no definitive reason has been confirmed, several factors are suspected to contribute to the rise of colorectal cancer in younger age groups. Higher consumption of processed foods, rising obesity rates, decreased physical activity, microplastics, and microbiome changes are all considered possible explanations that are under investigation. 

Risk Factors

There are several confirmed risk factors that contribute to an individual’s risk for colon cancer.  

Below are some of the factors that increase an individual’s colorectal cancer risk: 

• Alcohol use: Alcohol consumption has been linked to an increased risk of several types of cancer, including colorectal. When the body metabolizes alcohol, it produces acetaldehyde, a toxic substance that can damage DNA and proteins. Alcohol can also influence hormone levels and impair the absorption of certain nutrients.This risk is considered dose-dependent, meaning it increases with the amount of alcohol consumed. 
• Smoking and secondhand smoke exposure: Smoking and secondhand smoke increases your risk of many cancers, including colorectal. Tobacco smoke contains numerous carcinogens that can lead to genetic mutations and uncontrolled cell growth, ultimately resulting in cancer. The impact of smoking on colorectal cancer risk is directly proportional to the number of cigarettes you have smoked in your lifetime. Quitting smoking at any age can significantly reduce the risk of cancer and other smoking-related diseases. The body begins to repair itself almost immediately after quitting, with the risk of cancer decreasing over time. Even individuals who have smoked for many years can benefit from quitting, as the risk decreases with each year of abstinence. 
• Body mass index (BMI): Numerous studies have shown a link between higher BMI and an increased risk of various types of cancer, including colorectal. Excess body fat can lead to higher levels of estrogen and insulin, as well as increased production of insulin-like growth factors. These hormones can promote the development and growth of certain cancers. Higher BMI is also associated with chronic low-level inflammation, which can cause DNA damage over time and contribute to the development of cancer. Furthermore, high BMI can impair immune function, reducing the body's ability to fight off cancer cells. 
• Height: Research has consistently shown a correlation between height and an increased risk of several types of cancer, including colorectal. Taller individuals tend to have higher levels of IGF-1, a hormone that plays a critical role in growth and development. IGF-1 can promote cell proliferation and inhibit cell death, which may contribute to the development and progression of cancer. Taller individuals also have more cells in their body simply due to their size–which leads to a higher probability of cells mutating–and longer intestines, leading to prolonged contact between carcinogens and the intestinal surface.
• Family history: Family history plays a significant role in determining cancer risk. Studies have shown that having a first degree relative (parent or sibling) who has been diagnosed with colorectal cancer increases your personal colorectal cancer risk by 8-9%. This is further compounded by traits often shared amongst family members, such as dietary and lifestyle habits.
• Health conditions
  
  • Inflammatory bowel disease: Inflammatory bowel disease (IBD) is associated with an increased risk of certain types of cancer, primarily colorectal cancer. IBD is characterized by chronic inflammation of the gastrointestinal tract. It is important to note that this is distinct from irritable bowel syndrome (IBS), which is a common bowel disorder that causes abdominal pain, bloating, and changes in bowel movements. In IBD, persistent inflammation can lead to changes in the cells lining the colon and rectum, increasing the risk of colorectal cancer. The level of risk is influenced by factors such as the duration and severity of inflammation. Longer duration of active disease and more severe inflammation are associated with a higher risk of colorectal cancer. 
  • Cystic fibrosis: Cystic fibrosis is a genetic disorder characterized by the buildup of thick, sticky mucus in various organs, particularly the lungs and digestive system. It has been shown to dramatically increase the risk of developing colon cancer. 
  • Type 2 diabetes: Research has consistently shown that individuals with diabetes have an increased risk for certain types of cancer, including colorectal. This risk is particularly heightened in individuals with type 2 diabetes. Insulin resistance is believed to contribute to this link, along with chronic inflammation which is common amongst diabetics. 
  • BRCA1 genetic  mutation: BRCA1 (Breast Cancer gene 1) is a tumor suppressor gene, meaning its normal function is to help prevent the development of cancer by repairing damaged DNA and regulating cell growth. Mutations in the BRCA1 gene can interfere with its ability to carry out these functions effectively. While primarily associated with breast cancer risk, the BRCA1 genetic mutation also significantly increases the risk of colorectal cancer. 
• Gallbladder removal: Studies suggest that removal of the gallbladder may increase the risk of digestive cancers. After gallbladder removal, the body still produces bile, but the bile is released continuously into the small intestine rather than being stored in the gallbladder and released in response to meals. This change in bile flow can affect digestion and may potentially impact the metabolism of certain substances in the digestive tract.
• Red / processed meat consumption: Red meat consumption has been associated with several cancers, particularly colorectal cancer. Red meat contains compounds such as heme iron and saturated fats, which have been hypothesized to contribute to cancer risk through mechanisms like oxidative stress and inflammation. Processed meat often contains added nitrites and nitrates, which can lead to the formation of carcinogens during digestion, and are high in saturated fats and sodium, which have both been linked to an elevated risk of colorectal cancer. 

Several factors have been shown to have protective effects against colorectal cancer:

• Fruit and vegetable consumption: Fruits and vegetables are rich in various nutrients which have been shown to have protective effects against several cancers, including colorectal. These foods contain a variety of antioxidants, which help neutralize free radicals in the body, and reduce inflammation. They are also a good source of dietary fiber, which helps to maintain regular bowel movements and may contribute to the removal of potentially harmful substances from the colon.
• Fatty fish consumption: Oily fish, such as salmon, mackerel, trout, sardines, and herring, are rich in omega-3 fatty acids, protein, vitamins, and minerals. They are known to have various health benefits, including protective effects against colorectal cancer. 
• Coffee: Several studies have found that coffee consumption decreases your risk of certain types of cancer, including colorectal. The beneficial effects may be due to the presence of bioactive compounds in coffee, such as caffeine and polyphenols, which have antioxidant and anti-inflammatory properties. Most studies suggest that protective effects of coffee are observed with moderate consumption (typically 3-4 cups per day). It's important to recognize that individual responses to coffee intake may vary based on factors such as genetics, metabolism, and overall diet and lifestyle.
• Water intake: Water intake plays a significant role in maintaining overall health, and has been shown to reduce the risk of colorectal cancer. Adequate water intake helps dilute carcinogens, which reduces both the concentration of potential carcinogens and the time spent in both the bladder and digestive tract.
• Physical activity: Engaging in physical activity can lower your risk of developing several types of cancer through a combination of physiological, hormonal, and immunological changes. Physical activity can reduce inflammation, improve immune function, improve hormonal regulation, and lower insulin levels. The American Cancer Society recommends engaging in at least 150 minutes of moderate activity or 75 minutes of vigorous activity each week. However, data indicates that individuals can see significant incremental benefit with additional exercise.
• Calcium supplements: Several studies have shown that calcium supplementation can reduce the risk of colorectal cancer and adenomas (precancerous polyps). Calcium can bind to bile and fatty acids in the intestine, forming insoluble complexes that are excreted. This process may reduce the carcinogenic potential of these substances in the colon lining. Some studies suggest that calcium's protective effect may be enhanced when taken in combination with vitamin D, which aids in calcium absorption and also has potential anti-cancer properties.
• NSAIDs: Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen or naproxen, are a class of medications commonly used to relieve pain, reduce inflammation, and lower fever, and they have also been shown to reduce cancer risk with regular use. In addition to their anti-inflammatory properties, NSAIDs have been shown to inhibit cell proliferation, induce programmed cell death, suppress tumor growth, and modulate immune responses. While NSAIDs have been associated with potential benefits in cancer prevention, their use is not without risks. Long-term or high-dose NSAID use has been linked to gastrointestinal bleeding, ulcers, and perforation. Additionally, certain NSAIDs have been associated with an increased risk of cardiovascular events such as heart attack and stroke. 
• Statins: Statins are a class of prescription drugs that lower cholesterol levels and can reduce the risk of heart attack and stroke, and studies have shown that statins may also lower the risk of several cancers, including colorectal. While the exact mechanism is unknown, this could be due to several factors. Statins have anti-inflammatory properties that may inhibit the inflammatory processes involved in cancer development and progression.
• Blood type O: Individuals with blood type O have a lower risk of developing colorectal cancer compared to other blood types. 
• Hormone replacement therapy: Hormone replacement therapy (HRT)--used to relieve symptoms of menopause by replacing hormones whose levels have decreased–can impact cancer risk in various ways. Multiple studies have shown that HRT increases the risk of breast cancer and ovarian cancer. The risk increases with the duration of use, and decreases after stopping HRT. Conversely, HRT has been shown to decrease colorectal cancer risk. The mechanisms are not fully understood, but hormonal influences on the gastrointestinal tract are considered a likely factor.

Screening

The development of colorectal cancer is a gradual process that can take several years, often spanning a decade or more. Early detection of colorectal cancer has a dramatic impact on prognosis. The 5-year survival rate for localized cancer is 90-91%, but drops to just 13-18% once the cancer has spread to distant parts of the body.

The U.S. Preventive Services Task Force (USPSTF) recommends that adults aged 45 to 75 undergo regular colorectal cancer screening. Depending on your age and risk factors, the optimal colorectal cancer screening will vary:

• Medical history / physical exam: A thorough medical history and physical examination is often the best first test for possible colon cancer. Knowing your family history and evaluating any new or ongoing symptoms may lead your doctor to order further tests or refer you to a gastroenterologist even if you’re outside standard screening protocols. 
• Colonoscopy: A colonoscopy is the gold standard in colorectal cancer screening. It is the most complete screening method available, and allows doctors to identify and remove polyps or pre-cancer within the same procedure. Colonoscopies require preparation in advance of the procedure, and patients must follow a clear liquid diet for 1-3 days before the procedure to empty their stomach and bowel. Doctors will typically provide a light sedative and possibly pain medication to help you stay relaxed during the procedure itself. 
• Stool DNA test: Stool DNA tests, such as Cologuard, are noninvasive at-home stool tests recommended for adults 45 and older at average risk for colon cancer. The stool DNA Test detects microscopic amounts of blood in stool, as well as certain DNA changes and mutations found in cancerous tumors or precancerous polyps. 
• Fecal Occult Blood Test (FOBT) and Fecal Immunochemical Test (FIT): These tests are noninvasive at-home stool tests used to detect microscopic amounts of blood in the stool. They may not detect blood that has been released further up the digestive tract, such as the stomach. Though less sensitive than colonoscopies and stool DNA tests, they are significantly more affordable and available for purchase online. 
• Blood tests: Blood tests can show secondary conditions which may relate to colon cancer, as well as test directly for tumor markers: 
  
  • Complete Blood Count (CBC): This test measures the relative levels of various types of cells in the body. In individuals with colon cancer, red blood cell counts may be low (anemia). 
  • Carcinoembryonic Antigen (CEA): This protein is often high in individuals with colorectal cancer. CEA testing is also used to track the progress of treatments in previously-diagnosed individuals.
• Liquid biopsy: Liquid biopsy is an investigational cancer-detection technique which looks for DNA fragments in the blood to determine whether cancer is present. Though still in its infancy, this technology is promising, particularly in screening for hard-to-detect cancers or cancers whose symptoms are minimal or tend to appear only after they’ve spread. Colorectal cancer is one of many cancers which can be screened for via this method.