What is Lynch Syndrome
Lynch syndrome is an autosomal dominant disease (i. e., whose genes are passed from father or mother to son or daughter) associated with a hereditary predisposition to the development of several types of cancer, mainly colorectal, endometrial and other types of digestive and urinary tract cancers. It is one of the most common hereditary syndromes for cancer predisposition in the human species.
The disease is responsible for 2% to 3% of colorectal cancer cases in the world and for 5% of the occurrences of this neoplasm in Brazil, where about 34 thousand new cases are diagnosed per year.
The causes of Lynch syndrome are mutations in genes that control a specific type of repair when DNA is damaged. People with the disease have a 55% to 85% risk of developing colorectal cancer by age 70, while in the general population (individuals who do not have the syndrome) this risk is 4.5%.
In general, patients with Lynch syndrome who develop colorectal cancer are diagnosed around age 40, and the precursor lesion is more likely to be a single adenoma (polyp) of the colon – unlike the multiple adenomas seen in patients with adenomatous polyposis familial, the other main hereditary form of this type of cancer.
Women with Lynch syndrome have a 40% to 60% risk of developing endometrial cancer.
Other cancers associated with Lynch syndrome are low-grade skin, ovarian, stomach, urinary tract, pancreas, small intestine, and brain cancers.
Symptoms and signs of Lynch syndrome
Symptoms of Lynch syndrome are similar to those of other forms of colorectal cancer. Here they are:
- Blood in the stool;
- Change in the functioning of the intestinal tract (alternating diarrhea and constipation);
- Abdominal pain or discomfort;
- Weakness and anemia;
- Unexplained weight loss;
- Change in stool shape (very thin and long stools);
- Abdominal mass (tumor).
Lynch syndrome diagnosis
The specific diagnosis of Lynch syndrome is confirmed through genetic testing, but determining who should be tested is complex. This is because, unlike familial adenomatous polyposis, the syndrome has no phenotypic appearance.
Therefore, a suspicion of Lynch syndrome must be based on a detailed family history. Three elements must be considered in this analysis:
- Having three or more relatives with colorectal cancer or cancer associated with Lynch syndrome;
- Colorectal cancer in at least two generations of the family; and
- At least one case of colorectal cancer before age 50 in the family.
It is important to highlight that less than a third of patients with the syndrome meet all of these criteria. Therefore, observation of the tumor origin site (ascending and transverse colon), age at diagnosis and presence of any other tumor associated with the syndrome, such as those mentioned above, are sufficient to indicate some type of screening or direct DNA testing of syndrome genes.
The most used screening tests, because they are simpler, cheaper and provide invaluable information in treatment planning, are:
- Tumor immunohistochemistry (for Lynch syndrome proteins MLH1, MSH2, MSH6, PMS2); and
- Molecular study of microsatellite instability (exam that allows us to observe whether the type of defect typical of Lynch syndrome affects regions that contain multiple repetitions of DNA bases – called microsatellites).
If the patient has an abnormality in any of these tests, it still does not mean that they have Lynch syndrome, but it is strongly suggestive. In this case, we start to study mutations in the syndrome genes through DNA tests. If a genetic alteration is found, immediate family members are indicated for screening with periodic examinations for the early detection of any associated diseases.
Patients with the syndrome should have surveillance colonoscopy every 1 to 2 years and ongoing screening for cancers associated with the disease.
Some examples of exams that may be requested:
- Periodic imaging exams (tomography or magnetic resonance imaging) of the abdomen;
- Digestive endoscopy;
- Qualitative urine test.
Lesion resection is the most common treatment for Lynch syndrome. As most tumors of this type occur before the splenic flexure, the most recommended alternative is subtotal colectomy (leaving the rectosigmoid intact).
In some cases, the oncologist may recommend chemotherapy as part of the treatment.
These patients tend to have a better prognosis than colon cancer cases in the general population, and they respond very strongly to immunotherapy treatments.
The use of AAS (acetylsalicylic acid) in low dose reduces the number of cases of colorectal cancer in Lynch syndrome. Tracking the disease and periodic examinations performed after confirmation of the diagnosis are very efficient in the early detection of diseases and tumors resulting from it, greatly increasing the chance of success and cure in the treatment.