Hereditary nonpolyposis colorectal cancer is a hereditary form of colorectal cancer. It is transmitted by an autosomal dominant type. More often affects the proximal parts of the large intestine. Simultaneous or almost simultaneous development of several malignant tumors is possible. It is manifested by pain, stool disorders and intestinal obstruction phenomena. The diagnosis is established on the basis of family history, clinical symptoms and data from additional studies (colonoscopy, biopsy, genetic tests). Treatment is operative – radical or palliative.
ICD 10
C18 Malignant neoplasm of the colon
Meaning
Hereditary nonpolyposis colorectal cancer (HNPCC) is a malignant tumor of the colon caused by a hereditary mutation. It accounts for 3 to 8% of cases of colorectal cancer. It refers to hereditary forms of cancer. The risk of developing the disease during life with an established mutation is about 80%. A malignant tumor of the large intestine often occurs before the age of 50, that is, 10-15 years earlier than the average in the population. Patients with hereditary non-polypous colorectal carcinoma also have an increased likelihood of developing ovarian cancer, endometrial cancer, small intestine cancer, stomach cancer, kidney cancer and pancreatic cancer. The total risk of developing malignant tumors during life is more than 90%. The treatment is carried out by specialists in the field of clinical oncology, proctology and abdominal surgery.
Causes
The cause of the development of this pathology is usually mutations of genes for the repair of unpaired DNA bases. Normally, the repair allows you to repeatedly reduce the errors of DNA synthesis. The complex of proteins responsible for repair removes erroneous areas of deoxyribonucleic acid, and then “restores the gaps”. When mutating the genes responsible for this process, numerous uncorrectable DNA errors occur. The cells become less stable.
The presence of such mutations is confirmed during genetic studies. At the same time, there are clinical criteria that allow us to reasonably suspect the presence of hereditary non-polypous colorectal carcinoma. The probability of developing hereditary colorectal cancer when these criteria are detected may vary due to differences in genetic breakdowns and different levels of cell instability. The criteria include:
- The presence of three or more close relatives with colorectal cancer confirmed during histological examination. One of the three relatives must have the first degree of kinship with the other two. Along with colorectal cancer, the presence of kidney, small intestine and other cancers affected by HNPCC is taken into account.
- The development of the disease in representatives of two generations.
- At least one of the neoplasms was found in a patient under the age of 50.
For a more accurate prediction, oncologists distinguish three groups of patients, taking into account the propensity to develop hereditary non-polypous colorectal carcinoma: a low, medium and high risk group. The low-risk group includes the majority of the population. Members of this group have no family history of colon cancer, or it is detected in relatives not of the first degree of kinship or in relatives of the first degree of kinship over the age of 45. The average risk group includes patients with one first-degree relative who has colorectal cancer under the age of 45, or two first-degree relatives who have fallen ill at any age.
The high-risk group includes family members of a patient with established hereditary non-polypous colorectal carcinoma and various polypous syndromes. In addition, this group includes patients who have a family history of three or more cases of colon cancer within the maternal or paternal line (parent, grandfather, grandmother, aunt, uncle, sister, brother, nephew and niece) or two or more cases of colon cancer within the same line provided that at least one relative had multiple cancers or was diagnosed under the age of 45.
The probability of having children suffering from hereditary nonpolyposis colorectal cancer with a confirmed disease in one of the parents is 50%. Genetic studies during the intrauterine development of a child are possible, but in practice such diagnostics are carried out very rarely because of its low practical significance. The existing mutation may not manifest itself in any way during life (incomplete penetrance of the gene) or manifest itself with varying degrees of severity and at different ages (variable expressiveness of the gene), therefore it is impossible to assess the consequences of the presence of such a gene for a child in advance.
Symptoms
The clinical symptoms correspond to the classic colorectal cancer. Distinctive features are the younger age of patients and the predominant lesion of the proximal colon. Due to the high location of hereditary non-polypous colorectal carcinoma, blood in the feces is usually not visually determined, with significant blood loss, dark stools are possible, with repeated bleeding, anemia manifesting itself by weakness, dizziness, pallor of the skin and changes in the analysis of peripheral blood.
With hereditary nonpolyposis colorectal cancer, intestinal obstruction phenomena may occur. Initially, intestinal obstruction is partial, manifested by flatulence, delayed stools and sharp cramping pains, repeated after 10-15 minutes. With further growth of the tumor, conditions may occur that require emergency surgical intervention. Carcinomas of a sufficiently large size can be detected by palpation of the abdomen. With the progression of the disease, common signs of oncological damage are found: decreased appetite, weight loss up to cachexia, weakness, hyperthermia, etc.
Diagnostics
When making a diagnosis, family history, clinical manifestations and data from additional studies are taken into account. Patients are referred for colonoscopy, and endoscopic biopsy of tumor tissue is performed during the study. If the presence of hereditary non-polypous colorectal carcinoma is suspected, along with the standard morphological study of the material, a microsatellite variability study is performed. With a high level of microsatellite variability, special genetic tests are carried out.
Patients with hereditary non-polypous colorectal carcinoma are prescribed a stool test for latent blood, a peripheral blood test to detect anemia and a biochemical blood test to assess liver function. To detect metastases and primary tumors of other localization arising from this pathology, patients are referred for a comprehensive examination, which includes gastroscopy, pelvic ultrasound, cytological examination of endometrial aspirate, abdominal ultrasound, ultrasound of the retroperitoneal space, chest X-ray, scintigraphy of the entire skeleton and other studies.
Treatment
The treatment is surgical. Taking into account the high risk of developing new tumors, subtotal removal of the large intestine is usually performed with the creation of an ileorectal anastomosis. When lymph nodes are involved, lymphadenectomy is performed. In the presence of distant metastases, palliative surgical interventions aimed at eliminating the phenomena of intestinal obstruction are carried out. The prognosis is more favorable compared to non-hereditary forms of colorectal cancer.
Prognosis and prevention
Prevention of the development of hereditary non-polypous colorectal carcinoma includes regular examinations. The next of kin of patients with an already diagnosed HNPCC are recommended to have a colonoscopy every two years after the age of 20 and once a year after the age of 40. In addition, they should regularly take urine tests, and if pathological changes occur, they should be examined to exclude tumors of the kidneys and ureters. Women need to be examined annually by a gynecologist to exclude ovarian cancer and endometrial cancer. In some cases, preventive pangisterectomy is indicated. Distant relatives of patients with hereditary non-polypous colorectal carcinoma are advised to conduct a genetic study.