What is Hereditary Nonpolyposis Colon Cancer (Lynch Syndrome)?
Hereditary non-polyposis colorectal cancer (HNPCC), or Lynch syndrome, is a type of inherited condition that mostly leads to colorectal cancer (CRC). This means it’s passed down through families and is the leading inherited cause of CRC. This condition is identified by a strong family history of HNPCC related cancers, affecting close relatives like parents, siblings, or children across at least two generations. A key sign of this syndrome is at least one family member who was diagnosed with the disease before they turned 50.
What Causes Hereditary Nonpolyposis Colon Cancer (Lynch Syndrome)?
HNPCC, or Hereditary Nonpolyposis Colorectal Cancer, is linked with certain inherited changes in DNA repair genes. These genes usually fix small mistakes that happen when your DNA is copied for new cells. But, if there are issues with these repair genes, these mistakes aren’t fixed and can cause cells to grow out of control and form tumors.
Risk Factors and Frequency for Hereditary Nonpolyposis Colon Cancer (Lynch Syndrome)
Hereditary non-polyposis colorectal cancer (HNPCC) is a condition that affects about 1% to 6% of the White race population. People with HNPCC often develop colorectal cancer 10 to 15 years earlier than the average person. This condition is equally common in both men and women.
Signs and Symptoms of Hereditary Nonpolyposis Colon Cancer (Lynch Syndrome)
HNPCC, or Hereditary Non-Polyposis Colorectal Cancer, often goes undiagnosed. Traditionally, doctors would suspect this condition if a patient’s family history included colorectal cancer and other types of malignancies. Several criteria help identify people at risk.
The Amsterdam Criteria was introduced as a way to identify individuals at risk of HNPCC. It was later updated as the Amsterdam II Criteria to include other cancers associated with HNPCC.
Under the Amsterdam II criteria, someone might have HNPCC if they meet all the following:
- They have three or more relatives with specific types of cancer associated with Lynch syndrome, one of which must be a first-degree relative of the other two and these cancers can’t be attributed to familial adenomatous polyposis.
- At least two generations of their family have experienced these cancers.
- At least one family member was diagnosed with cancer before turning 50.
The Amsterdam II Criteria accurately diagnoses HNPCC 22% of the time (sensitivity), and correctly identifies those without the disorder 98% of the time (specificity).
Alternatively, the Bethesda Criteria guidelines were established to assist in identifying those who should further explore their tumor for instability in microsatellites, a certain type of DNA sequence. The revised Bethesda guidelines have a sensitivity of 82% and a specificity of 77% for detecting HNPCC.
People with HNPCC might experience symptoms such as:
- Gastrointestinal problems such as constipation, diarrhea, abdominal pain, cramping, and bloating.
- Blood in their stool, which might appear as visible blood loss or detected during specific tests.
- Dark, tar-like stools (melena).
- Iron deficiency.
- A decrease in appetite.
- Unexplained weight loss.
- General fatigue or weakness.
Testing for Hereditary Nonpolyposis Colon Cancer (Lynch Syndrome)
If you’ve been diagnosed with colon cancer (CRC), endometrial cancer under the age of 60 years, or you have a close family member with HNPCC related cancers, you might be recommended for a genetic evaluation for HNPCC. This is also advised for those with a strong family history of cancer that corresponds with certain established criteria.
As a first step in the genetic evaluation process, a tumor microsatellite instability (MSI) test and/or an immunohistochemistry (IHC) test may be performed. These tests help measure how much the DNA of the tumor cells has altered. If these tests show normal results – that is, absence of significant alteration and intact expression of certain proteins – it means HNPCC is usually not the cause. However, when these tests show substantial change or loss of expression of certain proteins, further evaluation may be needed.
Lastly, you may undergo germline testing, which checks alterations in certain genes (MLH1, MSH2, MSH6, and PMS2 or EPCAM). This test can confirm the diagnosis of HNPCC and should be offered to patients whose tumors showed significant changes in the MSI or IHC tests. Other candidates for this test may include those with strong clinical suspicion of HNPCC or who meet certain criteria, even if prior tumor testing was not feasible or done.
Treatment Options for Hereditary Nonpolyposis Colon Cancer (Lynch Syndrome)
If you have Lynch Syndrome, you should start having yearly physical check-ups at age 25 to 30. This is a general measure to help manage your condition. Lynch Syndrome is a genetic disorder that increases the risk of certain types of cancer, particularly colon cancer.
Surgery is often recommended for managing this condition. In cases of Lynch Syndrome with colon cancer or large growths that can’t be removed with a procedure called an endoscopy, a surgery called “total abdominal colectomy with ileorectal anastomosis” is often the first choice. This surgery involves removing the entire colon and then connecting the small intestine to the remaining part of the rectum. Afterwards, you’d continue having routine check-ups of your rectum every year.
For patients who can’t have their entire colon removed, a “segmental colectomy” may be suggested. This surgery involves only removing part of the colon that’s affected by cancer. After the procedure, those patients should also have routine check-ups of their colon every year.
If Lynch Syndrome and rectal cancer are present, the preferred surgical procedure is “total proctocolectomy with ileal pouch-anal anastomosis”. This involves removing the entire colon and rectum due to the high risk of developing colon cancer again if only the rectum is removed. In general, if rectal cancer is present, patients should continue having routine check-ups of their colon every year.
In addition to the above, women who are having their colon removed may also be advised to have their uterus, fallopian tubes, and ovaries removed to prevent the risk of developing womb and ovarian cancers. Women have these parts removed in a procedure called “prophylactic hysterectomy and bilateral salpingo-oophorectomy”.
A type of chemotherapy called “immunotherapy” can be beneficial in advanced cases of colorectal cancer that are characterized by a high degree of genetic changes, called “microsatellite instability”.
Besides surgery and chemotherapy, there are other strategies for managing and preventing cancer in Lynch Syndrome patients:
A. Preventive Surgery: Similar to the above, a woman could undergo a hysterectomy and salpingo-oophorectomy to reduce the risk of womb and ovarian cancer.
B. Chemoprevention: Aspirin and oral contraceptives might be suggested as they can help reduce the risk of certain cancers. Some research indicates that aspirin could possibly lower the risk of colorectal cancer in Lynch Syndrome patients, but more research is needed to confirm this. Using birth control pills (oral contraceptives), especially if they contain estrogen and progesterone, could also possibly reduce the risk of womb and ovarian cancer. However, this should be considered by women who are not currently planning to conceive. If you already have children or don’t plan to have more, this could be an option for you.
What else can Hereditary Nonpolyposis Colon Cancer (Lynch Syndrome) be?
When diagnosing Hereditary Nonpolyposis Colorectal Cancer (HNPCC), it’s important for doctors to think about other conditions that might cause similar symptoms. These include:
- Double somatic mutations in suspected Lynch syndrome
- Attenuated Familial Adenomatous Polyposis (AFAP) and MUTYH-Associated Polyposis (MAP)
- Constitutional Mismatch Repair Deficiency (CMMR-D) Syndrome
- Familial Colorectal Cancer Type X (FCCTX)
- Lynch-like syndrome
- Cronkhite-Canada syndrome
- Hyperplastic polyps
- Juvenile Polyposis Syndrome
- Lymphomatous Polyposis
- Nodular Lymphoid Hyperplasia
- Sporadic Colon Cancer
- Turcot Syndrome
- Cowden Disease
- Muir-Torre Syndrome
- Neurofibromatosis Type 1
- Peutz-Jeghers Syndrome
By exploring these possibilities and conducting appropriate tests, doctors can make sure they arrive at the correct diagnosis.
Surgical Treatment of Hereditary Nonpolyposis Colon Cancer (Lynch Syndrome)
Hereditary non-polyposis colorectal cancer (HNPCC), an inherited form of colon cancer, can be prevented and treated using a variety of surgical procedures. However, getting rid of the entire colon (total colectomy) is the only technique that can both treat any existing cancers and stop new ones from forming in the colon.
The surgeries that are most often done include:
- Subtotal colectomy: This is a procedure in which a part of the colon is removed.
- Total colectomy with ileostomy or ileoanal pull through: This involves removing the entire colon. With an ileostomy, the end of the small intestine is brought out through a hole in the abdomen, and a bag is attached to collect waste. In an ileoanal pull through, the small intestine is directly connected to the rectum, thus, eliminating the need for an external bag.
What to expect with Hereditary Nonpolyposis Colon Cancer (Lynch Syndrome)
Patients diagnosed with a condition known as HNPCC (Hereditary Nonpolyposis Colorectal Cancer) and colon cancer generally have better survival rates than individuals with colorectal cancer in the broader population, known as sporadic colon cancer. In fact, if you have HNPCC, your chances of surviving for five years after diagnosis are about 60%, while those with sporadic colon cancer typically have a survival rate of 40-50%.
It’s also worth noting that people with tumors that are MSI-positive— which means that the tumors have a genetic change known as microsatellite instability— tend to have improved survival rates.
Possible Complications When Diagnosed with Hereditary Nonpolyposis Colon Cancer (Lynch Syndrome)
People with HNPCC, a type of genetic disorder, have a higher chance of developing different types of cancers simultaneously or at different times. The most frequently seen cancer outside of the colon in those with HNPCC is endometrial cancer, which affects the lining of the uterus. People with HNPCC are also more likely to develop cancers of the ovary, stomach, small intestine, liver and bile duct system, renal pelvis and ureter (parts of the urinary system), brain (specifically glioma, a type of brain tumor), and skin tumors known as sebaceous neoplasms.
Moreover, the risk of pancreatic cancer, prostate cancer, breast cancer and cervical cancer also increases in individuals with HNPCC. There have also been a few reported cases of laryngeal (throat) cancer, blood cancers, adrenal gland tumors, and sarcomas (cancer of soft tissues like muscle) in individuals with HNPCC.
Associated Cancers:
- Endometrial cancer
- Ovarian cancer
- Stomach cancer
- Small intestines cancer
- Liver and bile duct system cancer
- Renal pelvis and ureter cancer
- Brain glioma
- Sebaceous neoplasms (skin tumors)
- Pancreatic cancer
- Prostate cancer
- Breast cancer
- Cervical cancer
- Laryngeal cancer
- Blood cancers
- Adrenal gland tumors
- Sarcomas
Preventing Hereditary Nonpolyposis Colon Cancer (Lynch Syndrome)
HNPCC, or Hereditary Non-polyposis Colorectal Cancer, is also known as Lynch syndrome. It’s a type of genetic trait that can be passed down through families, and it’s a common reason why some people might be at a higher risk of getting colorectal cancer, which is a type of cancer that affects the colon or rectum. Doctors use a method called colorectal cancer screening to check the colon and rectum for signs of cancer or growths, called polyps, which could turn into cancer.
People with a strong family history of colorectal cancers should consider early screening. This may involve a procedure called an endoscopy, which allows doctors to examine the inside of the body. Doctors recommend having this screening done every one to two years starting from the age of 25 and then every year from age 40. If a family member had colorectal cancer, the screening should ideally start 10 years before the age at which that family member was diagnosed.
There are different ways to check for colon cancer, including:
- A colonoscopy, where the doctor uses a long, thin tube to look at the entire colon and rectum
- A CT colonography, which is a type of X-ray that gives a detailed view of the colon and rectum
- A stool test for blood, which can pick up small amounts of blood in your stool that may be caused by cancer
- A sigmoidoscopy, which is similar to a colonoscopy but only looks at the last part of the colon
- A stool DNA test, which looks for certain DNA changes in cells that might indicate cancer.
