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Colorectal Cancer

Disease Details

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Description: Colorectal cancer is a type of cancer that starts in the colon or rectum, often developing from polyps on the inner lining that become cancerous over time.
Type: Colorectal cancer can be influenced by both inherited and sporadic factors. In terms of genetic transmission, it can be hereditary (due to inherited mutations) or sporadic (due to acquired mutations). Hereditary forms include conditions like Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer) and familial adenomatous polyposis, both of which follow an autosomal dominant pattern of inheritance.
Signs And Symptoms: The signs and symptoms of colorectal cancer depend on the location of the tumor in the bowel, and whether it has spread elsewhere in the body (metastasis). The classic warning signs include: worsening constipation, blood in the stool, decrease in stool caliber (thickness), loss of appetite, loss of weight, and nausea or vomiting in someone over 50 years old. Around 50% of people who have colorectal cancer do not report any symptoms.Rectal bleeding or anemia are high-risk symptoms in people over the age of 50. Weight loss and changes in a person's bowel habit are typically only concerning if they are associated with rectal bleeding.
Prognosis: Fewer than 600 genes are linked to outcomes in colorectal cancer. These include both unfavorable genes, where high expression is related to poor outcome, for example the heat shock 70 kDa protein 1 (HSPA1A), and favorable genes where high expression is associated with better survival, for example the putative RNA-binding protein 3 (RBM3). The prognosis is also correlated with a poor fidelity of the pre-mRNA splicing apparatus, and thus a high number of deviating alternative splicing.
Onset: The onset of colorectal cancer varies but typically affects individuals aged 50 and older. It develops gradually over many years, often starting from noncancerous polyps in the colon or rectum that can eventually become cancerous. Early stages may not show symptoms, which is why screening is crucial.
Prevalence: The prevalence of colorectal cancer varies by region and population, but it is generally one of the most common cancers worldwide. It is the third most common cancer diagnosed in both men and women in the United States. Prevalence rates can be influenced by factors such as age, diet, genetics, and lifestyle.
Epidemiology: Globally more than 1 million people get colorectal cancer every year resulting in about 715,000 deaths as of 2010 up from 490,000 in 1990.As of 2012, it is the second most common cause of cancer in women (9.2% of diagnoses) and the third most common in men (10.0%): 16 with it being the fourth most common cause of cancer death after lung, stomach, and liver cancer. It is more common in developed than developing countries. Global incidence varies 10-fold, with highest rates in Australia, New Zealand, Europe and the US and lowest rates in Africa and South-Central Asia.
Intractability: Colorectal cancer is not inherently intractable. Early detection and treatment can significantly improve outcomes. Treatments may include surgery, chemotherapy, radiation therapy, and targeted therapies. The effectiveness of treatment largely depends on the stage at which the cancer is diagnosed.
Disease Severity: Colorectal cancer severity ranges from early stage to advanced, depending on how far the cancer has spread. Early-stage colorectal cancer, often asymptomatic, is localized to the lining of the colon or rectum and is highly treatable. As it progresses to later stages, the cancer can invade deeper layers of the colon wall, nearby lymph nodes, or distant organs, significantly decreasing the prognosis and making treatment more complex.
Healthcare Professionals: Disease Ontology ID - DOID:9256
Pathophysiology: Colorectal cancer encompasses tumors in the colon and rectum. Its pathophysiology typically involves a sequence of genetic and epigenetic changes that transform normal colorectal epithelium into adenomatous polyps and eventually into invasive cancer. Key molecular mechanisms include chromosomal instability (CIN), microsatellite instability (MSI), and CpG island methylator phenotype (CIMP). Common genetic alterations involve mutations in the APC, KRAS, TP53, and MLH1 genes. These changes disrupt normal cellular processes such as cell growth, apoptosis, and DNA repair, leading to uncontrolled cell proliferation and tumor formation. Environmental and lifestyle factors, including diet and inflammation, can also contribute to the development and progression of colorectal cancer.
Carrier Status: Colorectal cancer is not typically associated with a simple "carrier status" like some genetic conditions. However, genetic factors can play a role in an individual's risk for developing colorectal cancer. Familial adenomatous polyposis (FAP) and Lynch syndrome (hereditary nonpolyposis colorectal cancer, HNPCC) are two inherited conditions that significantly increase the risk.

- **Familial adenomatous polyposis (FAP):** Individuals with a mutation in the APC gene can develop hundreds to thousands of polyps in the colon, which virtually guarantees the development of colorectal cancer if untreated.

- **Lynch syndrome (HNPCC):** Caused by inherited mutations in mismatch repair (MMR) genes such as MLH1, MSH2, MSH6, and PMS2, individuals with this syndrome have a higher risk of developing colorectal cancer often at a younger age.

Genetic testing can identify these mutations. Early detection and proactive management strategies can significantly reduce the risk and improve outcomes.
Mechanism: Colorectal cancer (CRC) development involves a complex interplay of genetic and environmental factors. Let's break down some of the key mechanisms and molecular pathways:

1. **Mechanism of Colorectal Cancer Development:**
- **Initiation:** The transformation of normal colonic epithelium into a cancerous state typically begins with genetic mutations.
- **Promotion:** These mutations lead to abnormal cell growth and the formation of benign adenomatous polyps.
- **Progression:** Over time, some of these polyps may accumulate additional mutations, becoming malignant and invasive.

2. **Molecular Mechanisms:**
- **APC/Beta-catenin Pathway:** Mutations in the APC gene are common in CRC and lead to the stabilization and accumulation of beta-catenin, promoting uncontrolled cell proliferation.
- **Microsatellite Instability (MSI):** Defects in the DNA mismatch repair (MMR) system lead to MSI, which results in an increased mutation rate across the genome. This is often seen in hereditary non-polyposis colorectal cancer (HNPCC or Lynch syndrome).
- **KRAS/BRAF Mutations:** Activating mutations in oncogenes like KRAS and BRAF contribute to increased cell growth and survival.
- **P53 Pathway:** Mutations in the TP53 tumor suppressor gene result in the loss of cell cycle control and apoptosis, allowing malignant cells to survive and proliferate.
- **PI3K/AKT Pathway:** Alterations in the PI3K/AKT signaling pathway can promote cell survival and growth, contributing to cancer progression.
- **TGF-β Signaling:** Disruption of the TGF-β (transforming growth factor-beta) pathway can lead to decreased cellular differentiation and increased proliferation and invasion.

Understanding these mechanisms is crucial for developing targeted therapies and improving diagnostic and prognostic strategies for colorectal cancer.
Treatment: The treatment of colorectal cancer can be aimed at cure or palliation. The decision on which aim to adopt depends on various factors, including the person's health and preferences, as well as the stage of the tumor. Assessment in multidisciplinary teams is a critical part of determining whether the patient is suitable for surgery or not. When colorectal cancer is caught early, surgery can be curative. However, when it is detected at later stages (for which metastases are present), this is less likely and treatment is often directed at palliation, to relieve symptoms caused by the tumour and keep the person as comfortable as possible.
Compassionate Use Treatment: Compassionate use treatment and off-label or experimental treatments provide additional options for patients with colorectal cancer, especially when standard treatments have been exhausted or are unsuitable.

1. **Compassionate Use Treatment**: This allows patients to access investigational drugs outside of clinical trials. These drugs have not yet received regulatory approval but might offer potential benefits. Each case is typically evaluated individually, and approval is required from regulatory authorities and the drug manufacturer.

2. **Off-label Treatments**: These are FDA-approved drugs used for purposes other than those originally approved. For example, some chemotherapy agents or targeted therapies approved for other cancers may be used off-label for colorectal cancer based on emerging evidence or oncologist discretion.

3. **Experimental Treatments**: These include drugs and therapies still undergoing clinical trials. Participation in clinical trials can provide access to novel medications, combination therapies, or advanced treatment modalities like immunotherapy, targeted therapies, or even personalized medicine approaches.

Patients should discuss these options thoroughly with their oncologist to understand the potential risks, benefits, and the current scientific evidence supporting their use.
Lifestyle Recommendations: Lifestyle recommendations for colorectal cancer prevention include:

1. **Diet**: Consume a diet high in fruits, vegetables, and whole grains. Limit red and processed meats.
2. **Exercise**: Engage in regular physical activity, aiming for at least 150 minutes of moderate aerobic exercise per week.
3. **Weight Management**: Maintain a healthy weight to reduce cancer risk.
4. **Alcohol**: Limit alcohol intake. For men, no more than two drinks per day; for women, no more than one.
5. **Smoking**: Avoid smoking and use of tobacco products.
6. **Regular Screening**: Follow recommended screening guidelines starting at age 45 or earlier if you have higher risk factors.
7. **Medications**: Consult with a healthcare provider about the use of aspirin or other anti-inflammatory drugs, which may reduce risk in some individuals.

Making these lifestyle changes can help lower the risk of developing colorectal cancer.
Medication: Medications for colorectal cancer often include chemotherapy drugs, targeted therapies, and sometimes immunotherapy. Common chemotherapy drugs used are 5-fluorouracil (5-FU), capecitabine (Xeloda), oxaliplatin (Eloxatin), and irinotecan (Camptosar). Targeted therapies may include bevacizumab (Avastin), cetuximab (Erbitux), and panitumumab (Vectibix). Immunotherapy options can include pembrolizumab (Keytruda) and nivolumab (Opdivo). The choice of medication depends on the stage and specific characteristics of the cancer.
Repurposable Drugs: There are several drugs originally designed for other conditions that are being considered for repurposing in the treatment of colorectal cancer. These include:

1. **Metformin** - commonly used for type 2 diabetes; shows potential antitumor activity.
2. **Aspirin** - an anti-inflammatory drug; some studies suggest it may reduce the risk of developing colorectal cancer.
3. **Statins** - cholesterol-lowering drugs; may have a role in reducing cancer cell growth.
4. **Disulfiram (Antabuse)** - used to treat chronic alcoholism; has demonstrated potential as an anticancer agent in some studies.
5. **Allopurinol** - used for gout; exhibits inhibitory effects on certain cellular processes linked to cancer.

Further research and clinical trials are needed to confirm the efficacy and safety of these repurposed drugs for colorectal cancer treatment.
Metabolites: Colorectal cancer (CRC) is associated with various metabolic alterations. Metabolites that have been studied in the context of CRC include amino acids, lipids, and nucleotides. Specific metabolites such as lactate, butyrate, and certain bile acids have been found to play a role in the progression of CRC. For instance, increased levels of lactate can indicate enhanced glycolysis, a common feature in cancer cells (Warburg effect). Butyrate, produced by gut microbiota, has a protective role against CRC, but its reduced levels are observed in CRC patients. Elevated levels of bile acids, particularly secondary bile acids, have been associated with an increased risk of CRC.

Your reference to "nan" appears to be incomplete or unclear. If you meant to inquire about a specific aspect related to colorectal cancer, such as a particular nanotechnology application or a more focused metabolic pathway, please provide additional context or clarify your query.
Nutraceuticals: Nutraceuticals for colorectal cancer include dietary supplements and functional foods that may support health and assist in disease management. Some common nutraceuticals studied for their potential benefits in colorectal cancer include:

1. **Curcumin**: An active component of turmeric, known for its anti-inflammatory and antioxidant properties. It may help inhibit cancer cell growth and metastasis.
2. **Resveratrol**: Found in grapes and berries, it exhibits anti-cancer properties through the inhibition of cell proliferation and induction of apoptosis in cancer cells.
3. **Omega-3 Fatty Acids**: Present in fish oil, they have anti-inflammatory effects and may reduce the risk of cancer development and progression.
4. **Probiotics and Prebiotics**: Beneficial bacteria and their food sources that may improve gut health and modulate immune response.
5. **Green Tea Extract**: Contains epigallocatechin-3-gallate (EGCG), which may help in the prevention of cancer cell growth.

Nanotechnology applications (nan) in colorectal cancer focus on diagnosis, treatment, and drug delivery. Key aspects include:

1. **Nanoparticles**: Used to deliver chemotherapeutic drugs directly to cancer cells, enhancing efficacy and reducing side effects.
2. **Early Detection**: Nanoparticles can be used in imaging techniques to detect tumors at an earlier stage through enhanced contrast in imaging procedures.
3. **Targeted Therapy**: Nanocarriers can be designed to target specific cancer cells, minimizing harm to healthy tissues.
4. **Multifunctional Platforms**: Nanoparticles can be engineered to combine diagnostics, therapy, and monitoring in one platform, known as theranostics.

Ongoing research is exploring the full potential of these approaches in colorectal cancer management.
Peptides: Peptides have shown promise in colorectal cancer (CRC) research and treatment. They can serve as therapeutic agents, targeting specific cancer cells to inhibit their growth or kill them directly. Additionally, peptides are being explored for use in vaccines to trigger an immune response against CRC cells. Nanotechnology offers advancements as well: nanoparticles can deliver drugs specifically to cancer cells, reducing side effects and improving efficacy. Nanoparticles can also be used in imaging to help detect CRC at earlier stages. Both peptides and nanotechnology are areas of active research and show potential for improving colorectal cancer outcomes.