Hereditary Nonpolyposis Colorectal Cancer (HNPCC): Symptoms, Causes, Treatment

What are the symptoms of hereditary nonpolyposis colorectal cancer?

Hereditary Nonpolyposis Colorectal Cancer (HNPCC) is a rare genetic disorder that increases the risk of developing colon cancer. The symptoms of HNPCC are similar to those of sporadic colon cancer, but they can also be more aggressive and develop at a younger age. Here are some common symptoms of HNPCC:

1. Colorectal bleeding: The most common symptom of HNPCC is rectal bleeding, which can be diagnosed with a colonoscopy or flexible sigmoidoscopy.
2. Abdominal pain: Abdominal pain, often accompanied by cramping, may be a symptom of HNPCC.
3. Changes in bowel movements: Changes in bowel movements, such as diarrhea or constipation, can be a sign of HNPCC.
4. Fatigue: Fatigue is a common symptom of HNPCC, which can be due to the presence of cancer or the treatment.
5. Weight loss: Weight loss can occur as a result of the cancer itself or as a result of treatment.
6. Abdominal mass: In some cases, an abdominal mass may be felt on physical examination.
7. Lack of symptoms: Many people with HNPCC do not experience symptoms until the cancer has progressed to an advanced stage.

In addition to these symptoms, individuals with HNPCC may also experience:

• Family history: A strong family history of colon cancer, particularly if multiple relatives have been affected at a young age.
• Personal history: A personal history of colon cancer or other cancers (e.g., endometrial, ovarian, stomach).
• Endometrial cancer: Women with HNPCC are at increased risk of developing endometrial cancer.
• Ovarian cancer: Women with HNPCC are also at increased risk of developing ovarian cancer.

It’s essential to note that HNPCC can be asymptomatic, and some individuals may not develop symptoms until the cancer has spread to other parts of the body. Regular screening and surveillance are crucial for early detection and effective treatment.

If you have concerns about your risk for HNPCC or experience any symptoms, consult a healthcare provider for further evaluation and guidance.

What are the causes of hereditary nonpolyposis colorectal cancer?

Hereditary Nonpolyposis Colorectal Cancer (HNPCC) is caused by germline mutations in one of the genes responsible for the DNA mismatch repair (MMR) system. The MMR system is a complex process that ensures the accurate transmission of genetic information from one generation to the next by repairing errors that occur during DNA replication.

The most common genes associated with HNPCC are:

1. MLH1: The MLH1 gene provides instructions for making a protein called MutL homolog 1, which is involved in the MMR process.
2. MSH2: The MSH2 gene provides instructions for making a protein called MutS homolog 2, which is also involved in the MMR process.
3. MSH6: The MSH6 gene provides instructions for making a protein called MutS homolog 6, which is also involved in the MMR process.
4. PMS2: The PMS2 gene provides instructions for making a protein called Postmeiotic segregation increased 2, which is involved in the MMR process.

Mutations in these genes can lead to impaired MMR function, which increases the risk of DNA mutations and genetic instability. This can result in an increased risk of developing cancer, particularly colorectal cancer.

Other genetic factors that may contribute to the development of HNPCC include:

1. Epigenetic changes: Epigenetic changes, such as methylation and histone modification, can affect gene expression and increase the risk of cancer.
2. Genomic instability: Genetic instability can arise from defects in other genes involved in DNA repair, such as BRCA1 and BRCA2.
3. Environmental factors: Exposure to environmental factors, such as tobacco smoke, radiation, and certain chemicals, may also contribute to the development of HNPCC.

It’s essential to note that HNPCC is a complex condition, and multiple genetic and environmental factors may interact to increase the risk of developing cancer. If you have concerns about your risk for HNPCC or experience symptoms, consult a healthcare provider for further evaluation and guidance.

How is the diagnosis of hereditary nonpolyposis colorectal cancer made?

The diagnosis of Hereditary Nonpolyposis Colorectal Cancer (HNPCC) is typically made through a combination of clinical evaluation, family history, and genetic testing. Here are the steps involved in making a diagnosis:

1. Clinical evaluation: A thorough medical history and physical examination are performed to identify symptoms, such as rectal bleeding, abdominal pain, or changes in bowel movements.
2. Family history: A detailed family history is taken to identify relatives with a history of colorectal cancer, especially at a young age (<50 years).
3. Colonoscopy: A colonoscopy is performed to visualize the colon and rectum and to detect any abnormalities, such as polyps or cancer.
4. Pathology report: If a biopsy or surgical specimen is obtained, the pathology report is reviewed to assess the presence of microsatellite instability (MSI) or mismatch repair (MMR) deficiency.
5. Genetic testing: Genetic testing is performed to identify mutations in the MLH1, MSH2, MSH6, and PMS2 genes, which are responsible for the mismatch repair system.
6. Microsatellite instability (MSI) analysis: MSI analysis is used to assess the ability of the tumor cells to repair DNA mismatches. Tumors with MSI-high (MSI-H) are more likely to have HNPCC.
7. Immunohistochemistry (IHC): IHC is used to assess the expression of MMR proteins (MLH1, MSH2, MSH6, and PMS2) in tumor tissue. Loss of expression of one or more MMR proteins suggests HNPCC.
8. Genetic counseling: Genetic counseling is provided to individuals with a suspected diagnosis of HNPCC to discuss the implications of the diagnosis, inheritance patterns, and options for genetic testing.

The International Collaboration on Cancer Risk Evaluation of Lynch Syndrome (riberLynch) criteria are used to diagnose HNPCC:

• Three or more relatives with colorectal cancer diagnosed at <70 years
• At least one relative diagnosed at <50 years
• Presence of synchronous or metachronous colorectal cancers
• Presence of other cancers associated with HNPCC (endometrial, ovarian, stomach)

If you have concerns about your risk for HNPCC or experience symptoms, consult a healthcare provider for further evaluation and guidance.

What is the treatment for hereditary nonpolyposis colorectal cancer?

The treatment for Hereditary Nonpolyposis Colorectal Cancer (HNPCC) typically involves a combination of surgical, chemotherapeutic, and supportive therapies. The goal of treatment is to remove the cancerous tumor, reduce the risk of recurrence, and manage symptoms. Here are some common treatment options:

1. Surgery: Surgery is usually the primary treatment for HNPCC. The type of surgery depends on the location and extent of the cancer:
   • Colectomy: Removal of the colon or rectum.
   • Proctocolectomy: Removal of the entire colon and rectum.
   • Proctosigmoidectomy: Removal of the lower part of the colon and rectum.
2. Chemotherapy: Chemotherapy may be used in addition to surgery to reduce the risk of recurrence and improve survival rates. Common chemotherapy regimens include:
   • FOLFOX (fluorouracil, leucovorin, oxaliplatin)
   • CAPOX (capecitabine, oxaliplatin)
   • FOLFIRI (fluorouracil, leucovorin, irinotecan)
3. Targeted therapies: Targeted therapies are used to specifically target genetic mutations in HNPCC tumors. Examples include:
   • Bevacizumab (Avastin): Inhibits blood vessel growth.
   • Erlotinib (Tarceva): Inhibits epidermal growth factor receptor (EGFR).
4. Supportive care: Supportive care measures are essential to manage symptoms and improve quality of life. These may include:
   • Pain management
   • Nutrition therapy
   • Laxatives or stool softeners
   • Anti-diarrheal medications
5. Surveillance: Surveillance is crucial after treatment to detect recurrences or new primary tumors early. Regular colonoscopies, endoscopies, and imaging studies are necessary.

It’s essential to work closely with a healthcare team to develop a personalized treatment plan based on individual needs and circumstances.

If you have concerns about your risk for HNPCC or experience symptoms, consult a healthcare provider for further evaluation and guidance.

What is the survival rate for hereditary nonpolyposis colorectal cancer?

The survival rate for Hereditary Nonpolyposis Colorectal Cancer (HNPCC) varies depending on the stage and treatment received. Here are some general statistics:

• 5-year survival rate: The 5-year survival rate for individuals with HNPCC is around 60-70%.
• 10-year survival rate: The 10-year survival rate is around 50-60%.
• 15-year survival rate: The 15-year survival rate is around 40-50%.

However, these statistics can vary depending on factors such as:

• Stage at diagnosis: Early-stage disease (stage I or II) has a better prognosis than advanced-stage disease (stage III or IV).
• Treatment received: Individuals who receive timely and effective treatment have a better prognosis than those who do not.
• Age at diagnosis: Younger individuals tend to have a better prognosis than older individuals.
• Genetic mutation: Individuals with certain genetic mutations, such as MLH1 or MSH2, may have a better prognosis than those with other genetic mutations.

It’s essential to note that HNPCC is a rare condition, and these statistics are based on limited data. Additionally, the survival rate can vary depending on individual circumstances.

Early detection and treatment are crucial in improving the prognosis for individuals with HNPCC. Regular screening and surveillance are essential for early detection and management of the disease.

If you have concerns about your risk for HNPCC or experience symptoms, consult a healthcare provider for further evaluation and guidance.