Hereditary nonpolyposis colorectal carcinoma: causes, symptoms, diagnosis, treatment

Hereditary non-lipoprotein colorectal carcinoma (NSCP) is an autosomal dominant disease, representing 3-5% of cases of colorectal cancer. Symptoms, primary diagnosis and treatment are similar to other forms of colorectal cancer. Suspicion of NCCP follows from an anamnesis and requires confirmation by genetic research. Patients also need to be monitored because of the possibility of other malignancies, especially endometrial and ovarian cancer.

Patients with one of several known mutations have a risk of developing colorectal cancer in 70-80% during life. In comparison with sporadic forms of colon cancer, NCCR develops at a younger age (on average 40 years) and the lesion is more likely to be observed proximal to the splenic angle. Previous colon diseases are usually represented by a single colonic adenoma in contrast to multiple adenomas observed in patients with familial adenomatous polyposis (EPS), which is another hereditary form of colorectal cancer.

However, similar to EPS, numerous extra-intestinal manifestations can be observed. Benign diseases include the appearance of spots like coffee with milk, sebaceous cysts and keratoacanthoma. The main associated malignant tumors are endometrial and ovarian tumors (39 and 9% risk, respectively, at the age of 70). Patients also have an increased risk of cancer of the ureter, renal pelvis, stomach, biliary tract and small intestine.

[1], [2], [3], [4]

Symptoms of hereditary nonpolyposis colorectal carcinoma

Symptoms and signs are similar to other forms of colorectal cancer. The same concerns the diagnosis and the main directions of treatment of the tumor itself. The specificity of the diagnosis of NSCP is confirmed by genetic research. However, it is difficult to accept the test result, because (in contrast to SAP) there are no typical clinical manifestations. Thus, the suspicion of NSCP requires a detailed study of the family history that coincides with the EPS, which should be collected from all young patients.

In accordance with the Amsterdam II criteria, all three of the following elements of the anamnesis should be present for the NCCR: (1) three or more relatives with EPS or malignancy associated with NSCP, (2) colorectal cancer observed in at least two generations, and (3) at least one case of EPS until age 50.

Diagnosis of hereditary nonpolyposis colorectal carcinoma

Patients who meet these criteria need to examine the tumor tissue for a DNA change, the so-called microsatellite variability (MSI). If a significant MSI is detected, a genetic test for the specific NRCC mutations is shown. Other authors use additional criteria (eg, Bethesda criteria) to proceed with the MSI study. If the MSI study is not performed at this facility, the patient should be referred to a specialized center.

Patients with confirmed NCCC require further screening for another malignant tumor. The annual endometrial aspiration and transvaginal ultrasound are recommended for the detection of endometrial cancer. For the diagnosis of ovarian cancer, studies include annual transvaginal ultrasound and serum determination in the CA 125 level. Prophylactic hysterectomy and ovarian removal are also a method of choice. Urinalysis is used to screen a kidney tumor.

Relatives of the first line of patients with NCCP should perform a colonoscopy every 1-2 years, starting at age 20 and annually after 40 years. Women - relatives of the first line - should annually be screened for endometrial cancer with ovarian cancer. More distant relatives need to conduct a genetic study; if the results of the study are negative, they should undergo colonoscopy similarly to patients with an average degree of risk.

[5], [6], [7], [8]