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Lynch syndrome is hereditary nonpolyposis colorectal cancer (HNPCC). It is the most common hereditary colorectal cancer syndrome, accounting for 3-5 percent of all colorectal cancer cases. What are the causes and symptoms of this colon cancer? How is Lynch syndrome treated?

Lynch syndrome ,hereditary nonpolyposis colorectal cancer(HNPCC -hereditary nonpolyposis colorectal cancer) was first described by dr. Henry Lynch in 1966. Families with Lynch syndrome were initially defined as having only colorectal cancer. Today we know that the spectrum of cancer in such families may also include other cancers. On this basis, we distinguish:

  • Lynch I syndrome - cancer affects only the large intestine
  • Lynch II syndrome - colorectal cancer is accompanied by malignant neoplasms of the uterus, ovary, stomach, small intestine, kidneys, ureter, and less often of the skin, bile ducts and central nervous system tumors

Lynch syndrome: causes

HNPCC is caused by an autosomal dominant mutation, which means that if one parent has cancer, the baby's risk is 50 percent. The mutation occurs in genes associated with mismatch repair (MMR). Mutations in the hMLH1 and hMSH2 genes are responsible for 80 percent of the identified changes in MMR, 10 percent are mutations in the hMSH6 MMR gene, and hPMS2 mutations have been detected in a few families. Proteins produced by MMR genes are involved in detecting and correcting errors that arise during DNA replication. A malfunction of the MMR gene leads to the accumulation of errors in DNA segments containing repetitive sequences (microsatellites). DNA errors that disrupt the function of genes involved in growth regulation can lead to the development of tumors.

About 85 percent of colorectal tumors in patients with Lynch syndrome show a high degree of microsatellite instability (MSI), a characteristic defect in MMR gene function.

Immunohistochemical (IHC) analysis of colon tumors for the expression of different MMR proteinsoften shows no staining of proteins corresponding to the mutant gene. At the same time, such a phenomenon is observed in only 15% of sporadic colon tumors. Therefore, it is proposed to test colon tumors for MSI and loss of MMR protein expression as a strategy to detect which colorectal cancer patients may be at risk of Lynch syndrome and require additional genetic evaluation.

Lynch syndrome: clinical features

  • Tendency to develop cancer at a young age - up to 50 years of age - on average in 44 years, however, there is a large variation in the age at which the diagnosis is made among families.
  • Most neoplasms are located proximal to the hepatic fold.
  • High risk of metachromic changes (in 10 years new cancer in the large intestine in about 40 percent of patients) and synchronous changes
  • Mainly the mucous type of cancer
  • 30 percent of members of these families have multiple cancers of various organs.
  • Endometrial (uterine) cancer is the second most common cancer in families with Lynch syndrome. The lifetime risk is 40-60 percent, while the cancer is extremely rare in the general population. In some families, the frequency of endometrial cancer may even exceed that of colon cancer. The risk of developing cancers of the urinary system, ovary, stomach, pancreas, and small intestine is also higher, estimated at 10-20 percent.

Lynch syndrome: diagnosis

There are no biological markers of this syndrome, therefore diagnosis is possible only on the basis of clinical criteria. The starting point for their creation were the Amsterdam Criteria:

  • three or more relatives with histologically proven colorectal cancer, including one first or two second degree relative
  • colorectal cancer that occurs in at least two generations
  • a family history of one or more colorectal cancer diagnosed before the age of 50
  • family polyposis excluded

However, since as many as 50 percent of families with Lynch disease do not meet these criteria, they have been extended. It is these revised Bethesda recommendations that identify the families in which Lynch syndrome should be suspected:

  • fulfillment of Amsterdam criteria
  • patients diagnosed with 2 cases from the Lynch syndrome spectrum, including synchronous and metachronic cases of colorectal cancer and other parenteral neoplasms
  • colorectal cancer patients with one relativefirst degree who developed the same tumor or another from the HNPCC spectrum before the age of 45 or who was diagnosed with adenoma in the large intestine before the age of 45
  • patients diagnosed with colorectal cancer or endometrial cancer before the age of 45
  • patients with cancer of the ascending part of the colon or rectum diagnosed before the age of 45, in the histological examination undifferentiated cancer, carcinoma solidum or carcinoma cribriforme
  • colorectal cancer patients under 45 years of age, signet ring cells on histological examination
  • patients with colorectal adenomas diagnosed before the age of 40

In family members meeting the Bethesda recommendations, screening for microsatellite DNA instability in tumor tissue should be considered.

Lynch syndrome: treatment and prevention

The high risk of cancer throughout life requires the use of specialized strategies to prevent cancer processes:

  • colon screening

Colonoscopy in the 20-25 year olds repeated every 1-2 years. The endoscopist should be vigilant of small or flat lesions that may be associated with a greater possibility of malignancy in patients with Lynch syndrome compared to the general population

  • screening for endometrial neoplasms

Experts recommend annual transvaginal ultrasound and endometrial biopsy, starting at 30-35 years of age. Unfortunately, there is no evidence that such a procedure is effective. For this reason, women who do not want to have more children should be advised to have a prophylactic hysterectomy (removal of the uterus) as a more reliable way to lower the risk of developing cancer.

  • screening for other cancers

The majority (~ 60%) of deaths in people with Lynch syndrome are due to the presence of malignant neoplasms other than colorectal cancer and endometrial cancer. Unfortunately, there is not enough data to propose appropriate surveillance programs.

Upper gastrointestinal endoscopy (gastroscopy) is recommended in patients with Lynch syndrome only in countries with high incidence of gastric cancer; Moreover, all carriers of the>25 mutation. year should be tested for Helicobacter pylori .

Urine cytology and ultrasound of the urinary tract are recommended only for MSH2 mutation carriers as part of research or when the results of such testsare systematically collected in the Lynch syndrome database.

  • prophylactic surgical treatment

They can be considered as an alternative to annual screening. Most patients who have regular colonoscopy do not need to do so. However, if the onset of adenomas early or many have occurred, or if the colonoscopy is painful, prophylactic colonectomy may be a good choice. Note that if a subtotal colonectomy has been performed, the remaining colon mucosa should be screened by flexible sigmoidoscopy.

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Category:

Oncology