Hereditary non-polyposis colorectal carcinoma (Lynch syndrome) is the name given to a type of colon cancer that is mainly due to hereditary factors and does not form polyps in the intestinal mucosa. The disease, which is also synonymously referred to as Lynch syndrome after the US surgeon T. Lynch, represents the most common form of hereditary colorectal cancer. A total of 6 mutated genes involved in the repair mechanism of defectively replicated DNA sequences have been identified as causative agents.
What is heriditary nonpolyposis colorectal cancer?
Hereditary non-polyposis colorectal carcinoma (HNPCC), also called Lynch syndrome after the U.S. surgeon Henry T. Lynch, is a colon cancer based on previously identified gene mutations and inherited in an autosomal dominant manner. This means that the gene defect(s) are not located on either sex chromosome X or Y and that even one mutant allele of a gene (heterozygous) can cause the disease. In the case of Lynch syndrome, about 75 percent of heterozygous carriers of the mutated genes are affected by the disease. Children of parents of whom either the father or the mother are carriers of the gene mutations are also 50 percent likely to become heterozygous carriers of the gene mutations. Approximately 90 percent of all colorectal cancers develop from polypoid tissue through the benign adenoma stage. In contrast, hereditary non-polyposis colorectal carcinoma is not related to any polyps that may be present in the intestinal mucosa. The development of Lynch syndrome tumors is attributed exclusively to a loss of function of the repair mechanism for defectively replicated DNA sequences. The likelihood of developing other cancers of the intestine or other organs in addition to HNPCC is greatly increased compared with individuals who do not have HNPCC.
Causes
HNPCC is caused by a defect in the repair mechanism of defectively replicated DNA sequences. The repair mechanism normally prevents replicated DNA pieces with incorrectly occupied nucleic bases from being used further. Repair proteins encoded by so-called tumor suppressor genes are involved in the mechanism. Mutations of several suppressor genes are known, almost always affecting the genes mlh1 on chromosome 3 and msh2 on chromosome 2. When repair proteins fail, cell mutations accumulate during the formation of new cells, resulting in the accumulation of defective cells in clones that behave largely autonomously and no longer respond to the usual growth limiters. They typically form the germ cell of a malignant tumor.
Symptoms, complaints, and signs
HNPCC causes few complaints and symptoms in its early stages. The first signs, such as blood in the stool, are nonspecific and may have various causes. As the disease progresses, periods of constipation and diarrhea alternate. Gradually, abdominal pain, weight loss and signs of anemia join in as typical accompanying symptoms. If lymph nodes of the mesentery, the retaining ligaments of the intestines, also react with swelling and tenderness, metastasis of HNPCC may already have occurred. The distinction between non-polypy HNPCC and colorectal cancer, which is much more common and has a 90 percent probability of developing from polyps of the intestinal mucosa, is not readily recognizable in the early stages on the basis of the non-specific symptoms. Only specifically applied differentiated diagnostic procedures provide the necessary clarity.
Diagnosis and progression
The causes of HNPCC disease are purely genetic, so that in conjunction with the autosomal dominant inheritance of the disease, familial statistics regarding HNPCC disease are sought for diagnostic purposes. In order to standardize the informative value of statistical parameters, the so-called Amsterdam I and Amsterdam II criteria were introduced in 1990. In this context, the Amsterdam I criteria can be used to detect colorectal HNPCC only and the Amsterdam II criteria can be used to additionally detect carcinomas at other sites within the genitourinary tract. The first condition of the Amsterdam criteria is that at least three family members, one of whom must be a 1st-degree relative of the other two family members, are confirmed to have HNPCC disease.The 2nd condition is fulfilled if the diseases occurred in at least two consecutive generations. The third condition was that the disease occurred in one of the affected persons at the age of less than 50 years. If the family history or disease history is not known, the revised Bethesda criteria were introduced in 2004 for evaluation, one criterion of which must be met in each case to establish suspicion of HNPCC. Once the suspicion of HNPCC has been established, a number of diagnostic options are available to confirm or refute the suspicion. On the one hand, ultrasound and histological examinations are useful, and on the other hand, molecular genetic examinations can provide evidence for the presence of mutated suppressor genes. The course of the disease-untreated-is severe.
Complications
Lynch syndrome is a serious disease. It can lead to death if left untreated and, even with treatment, is associated with a reduction in life expectancy in many cases. In most cases, Lynch syndrome primarily causes bloody bowel movements. This can trigger a panic attack in many people. Furthermore, patients suffer from diarrhea and constipation and thus a reduction in quality of life. There is weight loss and often severe abdominal pain and anemia. Furthermore, affected individuals may lose consciousness and even lapse into a coma. Swelling and pain occur. Without treatment of Lynch syndrome, metastasis will occur, resulting in colon cancer. As a rule, cancers can only be treated well if they are diagnosed at an early stage. It is not uncommon for those affected to suffer from depression and other psychological upsets in addition to the physical symptoms. Likewise, the patient’s relatives may also be affected by these upsets. Lynch syndrome can be removed by surgical intervention. However, the further course of the disease depends on the diagnosis and the spread of the tumor, so a positive course of the disease cannot be predicted in every case.
When should you go to the doctor?
If there is repeated blood in the urine, there is cause for concern. A visit to the doctor is necessary to clarify the causes. If there are abnormalities in digestion, an examination of the symptoms should be made. If diarrhea or constipation occurs, a doctor should be consulted to initiate treatment. If the affected person loses weight, the organism may be undernourished. It is therefore advisable to have it examined by a doctor in time. In case of persistent as well as regularly recurring abdominal pain or abdominal discomfort, consultation with a doctor is necessary. If there are swellings, growths or skin abnormalities, a visit to the doctor is also necessary. If there is an increase in existing symptoms or the appearance of new symptoms, this is considered unusual and should be investigated. If there is pain or tenderness, a visit to the doctor is necessary. If there is dizziness, a general feeling of illness, nausea and vomiting, a doctor should be consulted. If the affected person suffers from a decrease in performance, apathy or weakness, this health condition should be discussed with a doctor. Sleep disturbances, concentration problems as well as attention deficits are complaints that can indicate serious impairments. Therefore, a visit to the doctor is recommended as soon as the affected person experiences these irregularities for several weeks.
Treatment and therapy
Treatment of hereditary non-polyposis colorectal carcinoma consists exclusively of its surgical removal. There is no drug or other treatment that could cure the cancer. Therefore, it is of great value in terms of a high success rate if any HNPCC that has occurred is detected and removed as early as possible. In some cases, it may be necessary to perform radiation therapy to the diseased tissue combined with chemotherapy before surgery.
Outlook and prognosis
With early treatment of hereditary non-polyposis colorectal carcinoma, also called Lynch syndrome, there is a good prognosis regarding cure.However, since it is a hereditary increased risk for colorectal cancer and other forms of cancer, the patient should have continuous follow-up examinations for healed colorectal cancer and screening examinations for other cancers. If the tumor is still limited and has not metastasized, there is no need for chemotherapy after its complete surgical removal. With adherence to constant follow-up and screening, a normal life expectancy can be assumed. Not all patients with this genetic defect will develop cancer during their lifetime. However, the probability is very high. For example, it has been found that up to the age of 80, 80 percent of all affected individuals will develop colorectal cancer. If metastases have already developed or if other organs are affected by a tumor in parallel with the colorectal cancer, the prognosis often deteriorates drastically. Parallel tumors, each of which has not yet metastasized, can be treated independently and completely cured. After metastases have formed, various therapeutic measures such as chemotherapy or radiation can be used in an attempt to delay cancer growth and prolong the patient’s life. To increase the quality of life in severe cases, in addition to the known treatment options, the psychological care of the patient often contributes.
Prevention
Preventive measures to avoid HNPCC are nonexistent because the main cause is tumor suppressor genes, which largely lose their ability to repair miscopied DNA sequences due to mutations. In addition, a lifestyle that supports the immune system can also be considered a conditional preventive measure. The most important preventive measures for individuals who belong to the vulnerable group because of their family history or because of molecular genetic testing are regular awareness of cancer screening such as colonoscopy and other early detection measures.
Follow-up
Follow-up of hereditary non-polyposis colorectal cancer begins with regular check-ups. These are to ensure that the healed colorectal cancer does not recur. If it is a limited tumor without metastases that could be completely removed, these follow-up examinations are equally important. Depending on the severity of the individual case, psychological care may be useful. This can take place as part of prevention as well as during follow-up treatment. For a good quality of life, it is important to follow the medical advice given by the medical professionals. To support the immune system, a healthy lifestyle is essential. Above all, this includes a balanced, nutrient-rich diet, often in combination with avoiding certain foods. If molecular genetic testing indicates that the risk potential is quite high, cancer prevention is clearly the priority. Patients who are at risk because of their family history should undergo regular colonoscopy and other screening measures. For acute symptoms, there are also home remedies and self-help tips for everyday life. Light food and painkillers on a natural basis reduce the abdominal pain that occurs. If swelling occurs, a gentle massage or a cooling wrap will help. In addition, patients should listen to their doctor and take it easy.
Here’s what you can do yourself
Lynch syndrome requires medical therapy in any case. The acute symptoms of Lynch syndrome can be relieved by a number of home remedies and self-help measures. Diarrhea can be reduced by changing the diet, while natural painkillers can be taken for abdominal pain. For swelling, cooling compresses are recommended, as well as gentle massages of the affected areas. After the carcinoma has been surgically removed, the patient must take it easy and otherwise follow the doctor’s instructions. In most cases, an individual diet is recommended, consisting of a light diet, low-salt meals, and avoidance of coffee, alcohol, and other stimulants. Recovery can be aided by taking extra care of the site of the procedure. Bleeding and swelling may occur, especially in the first few days. These can be reduced with calendula ointment and preparations with arnica or devil’s claw.Women who have once had Lynch syndrome should arrange for early examination of the child if they become pregnant. The child should be examined again in detail after birth and must attend cancer screening regularly throughout life.