Lynch syndrome is a hereditary non-polyposis colon cancer. Signs and treatment of lynch syndrome Clinical criteria for lynch syndrome

17.05.2020

annotation scientific article on clinical medicine, the author of the scientific work - Alla Petrovna Chudina

201 families were selected from the Moscow oncogenetic register, where there were cases of colon cancer in relatives of the 1st degree of relationship, the families were under observation for at least 5 years. The group is divided into 3 subgroups: 6 families - with Lynch syndrome (hereditary non-polyposis colon cancer), 36 - cancerous families, non-Lynch syndrome and 159 - non-cancerous families. Comparative analysis showed that families with Lynch's syndrome significantly differ from families of the other two subgroups in the following characteristics: 1) burden of cancer - more than 60% of relatives over 20 years old are sick; 2) high incidence of multiple tumors in women (57.1%); 3) the colon (cancer is affected more often than the rectum; 4) in women, cancer of the uterine body is the second localization after colorectal cancer; 5) the first malignant neoplasms appear 10-20 years earlier, and patients live with a tumor for 5-7 years longer than in the other two groups; 6) over 5 years of follow-up, new cases of cancer occurred in 50% of families with I-degree relatives and in 83% of families with I- III degree kinship. Cancer families differed from non-cancerous ones only in the overall burden of cancer (MS - 35.6%, HeRS - 12.5%) and in the frequency of new cases in relatives of I-III degrees of relationship (MS - 33.3%, HeRS - 10.7 %).

Text of scientific work on the topic "Lynch syndrome and sporadic colorectal cancer: clinical and genealogical features"

LITERATURE

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UDC 616.345 / .35-006.6-092: 612.6.05] -07

A. P. Chudina

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Received 05/11/11

LINCH SYNDROME AND SPORADIC COLORECTAL CANCER: CLINICAL AND GENEALOGICAL FEATURES

Russian Cancer Research Center. N. N. Blokhina (director - academician RAS M. I. Davydov) RAMS, Moscow

201 families were selected from the Moscow oncogenetic register, where there were cases of colon cancer in relatives of the 1st degree of relationship, the families were under observation for at least 5 years. The group is divided into 3 subgroups: 6 families - with Lynch syndrome (hereditary non-polyposis colon cancer), 36 - cancerous families, non-Lynch syndrome and 159 - non-cancerous families. Comparative analysis showed that families with Lynch's syndrome significantly differ from families of the other two subgroups in the following characteristics: 1) burden of cancer - more than 60% of relatives over 20 are sick; 2) high incidence of multiple tumors in women (57.1%); 3) the colon (cancer is affected more often than the rectum; 4) in women, cancer of the body of the uterus is the second localization after colorectal cancer; 5) the first malignant neoplasms appear 10-20 years earlier, and patients live with a tumor for 5-7 years longer than in the other two groups; 6) over 5 years of follow-up, new cases of cancer occurred in 50% of families with relatives of the 1st degree of relationship and in 83% of families with relatives of the 1st-3rd degree of relationship. Cancer families differed from non-cancerous ones only in the overall burden of cancer (MS - 35.6%, HeRS - 12.5%) and in the frequency of new cases in relatives of I-III degrees of relationship (MS - 33.3%, HeRS - 10.7 %).

Key words: Lynch syndrome, hereditary non-polyposis colorectal cancer, cancer families

LYNCH SYNDROME AND SPORADIC COLORECTAL CANCER: CLINICAL AND GENEALOGICAL FEATURES

P. A. Herzen Moscow Oncology Research Institute, Ministry of Health and Social Development of the Russian Federation, Moscow

Two hundred and one families that had cases of colorectal cancer among first-degree relatives and had been followed up for at least 5 years were selected from the Moscow Familial Cancer Registry and divided into 3 groups: 1) 6 families with Lynch syndrome (hereditary nonpolyposis colorectal cancer); 2) 36 cancer families without Lynch syndrome; 3) 159 noncancer families. Comparative analysis has shown that the families with Lynch syndrome significantly differ from those of two other subgroups in the following respects: 1) hereditary cancer loading (cancer cases in more than 60% of relatives over 20years of age); 2) high incidence rates for multiple cancers in women; 3) more common cancer involvement of the colon than the rectus; 4) cancer of the corpus uteri is a second malignancy after colorectal cancer among women; 5) primary malignancies occur 10-20 years earlier with the tumor-specific survival being 5-7years longer than in the two other groups; 6) during a 5-year follow-up, new cancer cases occurred among first-degree and first-to-third-degree relatives in 50 and 83% of the families, respectively. The cancer families differed from noncancer ones only in general hereditary cancer loading (35.6 versus 12.5%) and in the rate of new cases in first-to-third relatives (33.3% versus 10.7%).

Key words: Lynch syndrome, hereditary nonpolyposis colorectal cancer, cancer families

The accumulation of colon cancer (colorectal cancer - colorectal cancer) in families may be due to the inheritance of one of the mutant genes. These are primarily genes associated with the syndrome of hereditary nonpolyposis colon cancer (HNPCC) - Lynch syndrome (genes MSH2, MLH1, PMS1, PMS2, MSH6, etc.), as well as genes of hereditary polyposis of the gastrointestinal tract, mainly familial colon adenomatosis (APC gene). The risk of cancer in Lynch syndrome and familial adenomatosis is about 90%.

For correspondence: Alla Petrovna Chudina - Cand. honey. sciences, led. scientific. sotr. dep. chemical carcinogenesis; 115478, Moscow, Kashirskoe highway, 24; [email protected]

The precise identification of the carrier of the mutant gene using molecular genetic methods cannot currently be widely used for screening hereditarily predisposed people due to the complexity and high cost of methods. Clinical and genealogical analysis of pedigrees not only helps to narrow the area of \u200b\u200bsearching for persons at high risk for possible further molecular genetic identification, but in many cases it is still the only available method for identifying hereditary predisposition. Therefore, the improvement of this method, the refinement of its criteria is relevant to this day.

The aim of this work was to study the relationship of family accumulation of CRC as the main symptom of syndromes.

rum Lynch (sLynch) with other known criteria, such as a younger age of tumor onset, longer life expectancy after diagnosis, primary multiplicity of neoplasms. Objective assessment The values \u200b\u200bof the listed criteria in our study were the frequency of new cases of malignant neoplasms that arose during the 5-year follow-up.

The work was carried out on the materials of the Moscow Onco-Genetic Registry (MOGR), which has been functioning since 1990 at the Russian Cancer Research Center named after V.I. NN Blokhin and on the basis of the oncological dispensary number 4 in Moscow. The MOGR includes data on the pedigrees of more than 6 thousand cancer patients. The information was obtained as a result of postal, less often telephone or personal interviews with patients. Oncological diagnoses of all probands and some of their relatives were verified by hospital discharge, outpatient records and according to the Moscow Cancer Registry. Since 1995, monitoring of information about families included in the register 5 years ago and more has been carried out. Information about probands and some relatives is first specified by outpatient cards and by the database of the cancer registry. Families who can be contacted through probands or relatives are invited to re-survey.

Of 1185 re-interviewed families, 201 were selected, where patients with CRC were found among relatives of the 1st degree of kinship (including the proband). The sample is divided into 3 groups. The 1st group included 6 families with sLinch. These are 5 families where mutations in the IMBI2 (4 families) and LMLI1 (1 family) genes were previously identified, and 1 family that has not been studied molecularly genetically, but with a typical clinical and genealogical picture of Linch. Group 2 included 36 families with 3 or more cases of malignant neoplasms (MN) different localizations in relatives who are in the I degree of kinship to one of the patients, and the defeat affected two generations or more. Neither primary multiplicity nor age at onset of the disease were taken into account. The group is designated as cancer families (MS). Group 3 consisted of 159 families, conventionally designated as non-cancerous (HePC), although 72 of them had malignant neoplasms in 1-2 relatives of the 1st degree of kinship, excluding probands.

The groups were compared in terms of the frequency of MF patients among relatives of the 1st degree of relationship, the frequency of primary multiple lesions, the relative frequency of cancer in some localizations, the age of MF onset, the patient's life expectancy after diagnosis.

tumor growth and the frequency of families with new cancers. Since families have been observed for different periods of time, but not less than 5 years, information related only to this period of observation was used in the work.

To analyze and evaluate the results obtained, standard biometric methods, Excel 5.0 software package, and also some methods of on-coepidemiology were used.

In the compared groups, the number of relatives was approximately the same. On average, there were 5-6 relatives per family, including probands. In all groups there were more women than men due to the greater number of women among the probands. In the cLinch group, only women were probands. The most numerous were families of the MS group, the least - the cLynch group, however, these differences are statistically insignificant.

The family history of cancer was assessed by the overall frequency of patients with any malfunctioning among relatives of the 1st degree of relationship. It was the highest in the cLynch group: by the 1st registration, the frequency of patients among all relatives who reached 20 years old was 61.5%. This is significantly higher than the similar frequency of MN in relatives in the other two groups: 35.6% in the MS group and 10.5% in the HeRS group (p< 0,01). Во всех группах частота больных среди женщин была несколько выше, чем среди мужчин. Наибольшая частота онкологических больных была среди женщин из группы сЛинча (66,7%).

One of the signs of hereditary forms of cancer is the high incidence of multiple lesions. According to various authors, the frequency of multiple primary malignant neoplasms (PMN) among cancer patients ranges from 0.04 to 11% (more often 3-6%). Table 1 shows the frequency of PMN in probands and relatives of the 1st degree of kinship in the groups studied by us.

In the NRS group, the frequency of patients with PMN was approximately in line with the literature data (ranged from 2.6 to 9.3%). In total, out of 243 patients in this group, 14 had PMN (5.8%). In the MS group, the frequency of probands with PMZN was slightly higher than in the HeRS group, but it turned out to be unexpectedly low in relatives - only 1 case per 68 patients. In total, 6 (5.8%) patients out of 103 had PMZN, i.e., the MS group as a whole did not differ from the HeRS group.

In the cLynch group, the frequency of patients with PMN was high in women, both probands and relatives (50.0 and 62.5%, respectively). The difference with HeRS and MS is statistically significant (p< 0,01). Из 8 больных муж-

The frequency of patients with PMZN according to the 1st family registration (probands and relatives of the 1st degree of relationship)

Table 1

Group (number of families) Patients Frequency of patients with PMN *

probands relatives of the I degree of relationship

sLincha (6) Total 6 0 8 8

S PMZN 3 5 1

(% + m) (50.0 + 22.4) ** (62.5 + 17.1) *** (12.5 + 11.7)

RS (36) Total 294 * 6 38 30

S PMZN 4 1 1 0

(% + m) (13.8 + 6.4) (16.7 + 15.2) (2.6 + 2.6)

NonRS (159) Total 116 43 46 38

S PMZN 6 4 3 1

(% + m) (5.2 + 2.1) (9.3 + 4.4) (6.5 + 3.6) (2.6 + 2.6)

Note. * - the frequency of patients with PMN is calculated for the total number of patients; ** - the difference with the HeRS group is significant (p< 0,01); *** - различие с группами РС и НеРС достоверно (р < 0,01); 4* - у 1 пробанда-женщины было доброкачественное новообразование.

rank in this group, only 1 had PMZN (3 CRR). The obtained result, possibly, indicates that the high frequency of PMZN is characteristic only for women with lynch. However, it cannot be ruled out that for more of observations and in men with the syndrome, the frequency of PMZN will be increased. In total, 9 (40.9%) of 22 patients had PMN.

During 5 years of follow-up, patients from all three groups experienced repeated cases of MN. This, however, did not significantly affect the results: as at the first registration, the highest incidence of PMN was in women from the Lynch group and there were no significant differences between the MS and HeRS groups.

An analysis of the relative frequency of MN of some localizations in women and men is presented in Table. 2 and 3.

The analysis includes MN that arose before the 1st family registration, as well as within 5 years of follow-up. For primary multiplicity, each tumor was counted separately. Since all 3 groups were selected based on the presence of patients with cancer of the colon and / or rectum, these tumors constituted the majority. Some localizations are represented by 1-2 cases; they are included in the tables only in the total amount of neoplasms.

In noncancerous families, colon and rectal cancer occurred with the same frequency: 32% in women and 33% in men. In the MS group, men also had the same incidence of colon and rectal cancer, 27.5% each, while women had colon cancer more often than rectal cancer (24.7% and 16.9%). According to statistical data on the structure of cancer incidence in Russia and the CIS countries for 2003, in men, cancer of the colon and rectum has approximately the same frequency (5.4 and 5.0%), and in women, colon cancer occupies a slightly higher place ( 6.8 and 5%).

In the cLinch group, both women and men, colon cancer occurred significantly more often than rectal cancer, respectively, in women 31.3 and 12.5%, and in men 66.7 and 25%. Apparently, this is due to a more frequent lesion of the proximal colon in hereditary colorectal cancer. Of the other localizations of cancer in the cLinch group, there was only 1 case in men - a brain tumor. In women from the lynch group, the 2nd place is taken by cancer of the uterine body - 18.8%, which is significantly higher than the frequency of this form of cancer in the HeRS group - 3.4% (p< 0,05). В группе РС большое

Relative frequency of malignant neoplasms of some localizations in women

the place is occupied by breast cancer - 16.9%, as well as ovarian cancer - 9.1%. In this group, some families may have hereditary breast and ovarian cancer syndrome (BgCa1).

Young age of onset of MN and long life expectancy with a tumor are also considered signs of hereditary cancer. The data on the average age of onset of MN and life expectancy with a tumor are presented in Table. 4.

The summary includes those who were already sick by the 1st family registration. In the case of primary multiplicity, the age of the first tumor was taken into account.

On average, the first MNs in family members from the sLinch group arose 10-20 years earlier than in relatives from the other two groups: the average age in the cLynch group was 44-48 years, in the MS group, 54-66 years, in the HeRS group, 54-64. of the year. The differences are significant (p< 0,01). В то же время в группах НеРС и РС встречались и очень молодые (22, 23 года), и очень старые (87, 93 года) больные. В группе сЛинча возрастной разброс был меньше: минимальный возраст 30 лет, максимальный - 69 лет. В группе сЛинча большинство больных заболели до 50 лет: 71,4% женщин и 87,5% мужчин. При этом 21,4% женщин и 25% мужчин заболели в возрасте до 40 лет. В двух других группах картина прямо противоположна: 70-80% больных заболели после 50 лет и из них большинство заболели после 60 лет. В этих группах частота тех, кто заболел до 40 лет, не превышала 10%.

Life expectancy with a tumor is an indicator that depends on many reasons, and above all on the level medical care in the place and during the residence of the sick person. But since the analyzed families were taken from one source, it was considered possible to analyze this indicator as well. Used data on those who fell ill before the 1st registration of the family. The indicator is calculated from the establishment of the diagnosis to the death of the patient, and for those who are alive, including the 5-year period after the 1st family registration (see Table 4).

The longest average life expectancy with a tumor was in female probands from the cLin-cha group - 14.8 years. Sick relatives from this group also lived longer compared to relatives from the other two groups (p< 0,05). Обращает на себя внимание то, что во всех группах продолжительность жизни пробандов была больше, чем родственников. В качестве

table 2

Group ROC RPK RTM RYa RMZh Total *

sLinch 10 31.3 ± 8.2 4 12.5 ± 5.9 ** 6 18.8 ± 6.9 *** 3 9.4 ± 5.2 2 6.3 ± 4.3 32

RS 19 24.7 ± 7.9 13 16.9 ± 4.3 ** 5 6.5 ± 2.8 7 9.1 ± 3.3 13 16.9 ± 4.3 77

HeRS 57 32.0 ± 3.5 57 32.0 ± 3.5 6 3.4 ± 1.4 6 3.4 ± 1.4 16 9.0 ± 2.1 178

Note. ROK - colon cancer, PKK - rectal cancer, RTM - cancer of the body of the uterus, OC - ovarian cancer, BC - breast cancer; * - including other localizations; ** - the difference with the HeRS group is significant (p< 0,01); *** - различие с группой НеРС достоверно (р < 0,05).

Table 3

Relative frequency of malignant neoplasms of some localizations in men

Group ROC RPK RZh RPZh RBrL Total *

abs. % abs. % abs. % abs. % abs. %

sLinch 8 66.7 ± 13.6 ** 3 25.0 ± 12.5 0 0 0 12

RS 11 27.5 ± 7.1 11 27.5 ± 7.1 3 7.5 ± 4.2 4 10.0 ± 4.7 2 5.0 ± 3.5 40

HeRS 31 33.0 ± 4.9 31 33.0 ± 4.9 13 13.8 ± 3.6 2 2.1 ± 1.5 6 6.4 ± 2.5 94

Note. ROK - colon cancer, PKK - rectal cancer, PC - stomach cancer, PC - pancreatic cancer,

RBRL - cancer of the bronchi and lung;

Including other localizations;

the difference with the HeRS and MS groups is significant (p< 0,05).

Table 4

Age of onset of MN and life expectancy of patients (M ± m)

Group of Probands Relatives of the I degree of kinship

women men women men

number of patients number of years number of patients number of years number of patients number of years number of patients number of years

age * 6 43.5 ± 2.6 *** 0 0 8 47.8 ± 4.4 *** 8 43.5 ± 2.6 ***

life expectancy ** 14.8 ± 4.74 * 10.2 ± 2.84 * 9.3 ± 4.24 *

age * 29 53.8 ± 1.8 6 58.7 ± 3.9 38 60.8 ± 2.4 30 65.7 ± 2.8

life span ** 9.3 ± 1.2 9.3 ± 2.6 4.3 ± 1.1 1.9 ± 0.4

age * 116 54.0 ± 1.1 43 57.0 ± 1.4 46 64.3 ± 2.2 38 62.8 ± 2.0

life span ** 9.6 ± 0.6 8.1 ± 0.7 2.9 ± 1.0 2.4 ± 0.7

Note. * - average age of onset of any MN. With PMZN, the age of the first tumor is taken; ** - life expectancy from the first oncological diagnosis to death, and for the living - including the 5-year period after the 1st family registration; *** - the difference with the HeRS and MS groups is significant ^< 0,01); 4* - различие с группами НеРС и РС достоверно ^ < 0,05).

Table 5

Frequency of families with new cases of MN in blood relatives and probands over a 5-year follow-up period

Frequency of families with new cases of MN

Family group Total families of relatives of I degree of kinship and probands of relatives of I-III degrees of kinship and probands

abs. % abs. %

sLinch 6 3 50.0 ± 20.4 * 5 83.3 ± 15.2 **

РС 36 5 13.8 ± 5.8 12 33.3 ± 7.9 *

HeRS 159 13 8.2 ± 2.2 17 10.7 ± 2.5

Note.

the difference with the HeRS group is significant (p< 0,05); ** - различие с группами НеРС и РС достоверно (p < 0,01).

explanations, it can be assumed that patients with a favorable course of the disease respond more willingly to the questionnaire. It is also possible that probands are not always precisely aware of the timing of the onset of the disease in relatives.

New MN arose in families of all three groups. Table 5 presents data on the frequency of families in which new malignancies were diagnosed in probands and blood relatives of I-III degrees of kinship over 5 years.

If we take into account only probands and relatives of the 1st degree of kinship, then new cases of MN occurred in 50% of families in the sLinch group, in 13.8% of families in the MS group and in 8.2% of families in the HeRS group. Differences are significant only between sLinch and HeRS (p< 0,05). В группе сЛинча новые ЗН возникли лишь у тех, кто был ранее болен (вторые-третьи опухоли). В двух других группах были как повторные, так и первичные случаи ЗН. Можно предполагать, что в семьях с сЛинча практически не осталось носителей генетически обусловленной предрасположенности к раку (некому болеть).

If we also take into account more distant relatives (up to the III degree of kinship), which were reported by probands, then new MNs appeared in 83% of families in the cLinch group, in 33% of families in the MS group, and in 13% of families in the HeRS group. Differences are significant between all groups (p< 0,01).

Conclusion

The study has shown that with sLin-cha, the frequency of patients with malaria among relatives of the 1st degree of kinship reaches 60% or more. More than half of sick women and 12.5% \u200b\u200bof men have multiple lesions. A feature of the spectrum of neoplasms in patients with Linch is more frequent

colonic inflammation compared to rectum and an increased incidence of uterine cancer. Neoplasms in family members with lynch develop 10-20 years earlier than in relatives from families without syndromic pathology. In this group, 71-88% of patients were under 50 years old, and 21-25% were under 40 years old. In the other two groups, the picture is exactly the opposite: 70-80% of patients fell ill after 50 years, and most of them after 60 years. In these groups, the frequency of those who fell ill before the age of 40 did not exceed 10%. The average life expectancy with a tumor in patients from the Lynch group is 5-7 years longer than in patients from the other two groups. Finally, new malfunctions in families with sLynch appear significantly more often within 5 years than in families of the other two groups. In the MS group, new cases of MN occurred somewhat more often than in non-ROS, but the difference became significant only if relatives up to the III degree of kinship were taken into account. In general, the group, apparently, is rather heterogeneous and mostly consists of families in which the accumulation of 3 cases of cancer or more is due to the action of several genes (polygenic type of inheritance), as well as the influence of environmental factors. It is obvious that only when monogenic heritability is established, all the declared signs of hereditary cancer are manifested in full.

LITERATURE

1. Malignant neoplasms in Russia and the CIS countries in 2003 - M., 2005.

2. Chudina A. P. // Vopr. oncol. - 2004. - T. 50, No. 5. - S. 540-543.

3. Yurin A.G. // Vopr. oncol. - 2003. - T. 49, No. 3. - S. 376-382.

Cancers growing from the tissues of the large intestine cause dyspeptic disorders. But some of the malignant neoplasms quickly invade adjacent tissues. Lynch syndrome is distinguished by these features.

Characteristic features of the syndrome

Non-polypous colorectal cancer, or Lynch's syndrome, is a malignant tumor that develops in the background genetic predisposition... The neoplasm affects the walls of the large intestine, localizing mainly on the right side.

Nonpolyposis colorectal cancer is transmitted in an autosomal dominant mode of inheritance, in which for development cancerous tumor in a child it is enough to have one “defective” gene in either parent.

Lynch syndrome is diagnosed in people of both sexes under the age of 50. And the first signs malignant neoplasm begin to disturb 5-6 years before.

The development of Lynch's syndrome is often accompanied by the formation of tumors in adjacent structures: small intestine, ovaries, biliary tract, stomach and other organs. Therefore, if such neoplasms are found among relatives, persons older 25 years it is recommended that the GI tract is examined twice a year to detect non-polyposis colorectal cancer.

There are two types cancer: Lynch-and Lynch-syndromes. The first neoplasm is localized within the large intestine. This type of syndrome is characterized by early development multiple tumors that are not preceded by polypous growths.

Lynch-differs in that, in addition to cancer, the patient has a colon adenocarcinoma and neoplasms in other parts of the body. More often, with this form of cancer, malignant cells penetrate into the genitals (in women) or into the parts of the digestive tract.

In the first case, the risk of developing uterine cancer reaches 30-60%. With Lynch-syndrome, patients have a 10-15% probability of developing tumors in other parts of the body.

The reasons

Lynch syndrome develops due to mutations in genes (PMS2, MSH6 and others) that are responsible for correcting similar mistakes... Multiple transformation is not excluded, which increases the likelihood of occurrence malignant tumor.

Each gene contains DNA, with the help of which information is transmitted to the processes taking place in the body. During growth and division, cells receive these data from their “progenitors”. However, sometimes errors occur when the code is transmitted.

In a normal state, cells, using their own resources, eliminate such anomalies. But individuals with a genetic predisposition (with mutated genes) lack this ability. As a result, there is a "layering" of errors, which leads to the transformation of cells into malignant ones.

Symptoms

Lynch syndrome develops suddenly. The appearance of the tumor is not preceded by clinical signs indicating the defeat of the large intestine.

The presence of a neoplasm in the organ is indicated by pain in the lower abdomen, diarrhea, lack of appetite and general weakness... Due to these phenomena, the patient develops anemia.

Cancer tumors of this type are located mainly in upper sections intestines, therefore, blood clots are not found in the feces.

Pain characteristics vary from patient to patient. More often, the symptom is aching or pulling. Less commonly, pain syndrome occurs in the form of seizures characteristic acute appendicitis and cholecystitis.

Non-polypous colorectal cancer types 1 and 2 are palpable when large sizes are reached. The tumor is distinguished by a knotty structure and a dense or soft consistency.

Over time, the neoplasm disintegrates, which is expressed in symptoms of acute intoxication of the body. If, as the tumor grows, it retains its own structure, then intestinal obstruction occurs.

During the period when the neoplasm gives metastases, general weakness is noted, elevated temperature body. During this period, the patient becomes emotionally unstable with pronounced tendencies to depression. In addition, malnutrition progresses due to inadequate nutrient intake and colon dysfunction.

In the case of the growth of a malignant tumor, symptoms of urination disorder occur. In women, with damage to the ovaries, menstrual irregularities are observed.

Diagnostics

The diagnosis of Lynch syndrome is based on the collection of information about the early cases of detection of this type of cancer among the next of kin. However, in order to prevent malignant neoplasm, general screening examinations are not carried out.

To diagnose the latter, enzyme immunoassay and a method by which microsatellite instability is determined are also used.

When the first signs of cancer appear, colonoscopy and irrioscopy are prescribed. Stool tests are also carried out for detection blood clots, Ultrasound, CT and MRI of the abdominal organs.

In the case of spread of metastases, other examination methods are used to identify the area of \u200b\u200bdamage by malignant cells.

Treatment and prevention

When Lynch syndrome is detected, subtotal colectomy, which removes the large intestine, is considered the best treatment. This method is more preferable for partial resection of the affected organ.

Surgical intervention is used if the removal of the large intestine has a positive effect on the patient's condition and improves the quality of life.

Chemotherapy in the treatment of non-polyposis colorectal cancer is applied based on the characteristics of each case.

The basis of prevention is the dynamic observation of patients at risk. Patients with Lynch syndrome should be regularly examined by an oncologist and gastroenterologist.

Also, a colonoscopy is performed every six months, starting from the age of 25. It is important that the patient does not miss the procedure. The maximum duration between colonoscopy sessions should not exceed 1-2 years.

For women at risk, in addition to surgery for non-polypologous colorectal cancer, hysterectomy and bilateral oophorectomy are often prescribed.

The first method involves removing the uterus. In a bilateral oophorectomy, the doctor completely resects the tissues of the ovaries and fallopian tubes.

The use of both methods can reduce the risk of developing cancer of these organs. Moreover, all three surgical interventions are usually performed at the same time.

The methods of prevention of Lynch syndrome in persons with a genetic predisposition include regular intake of vitamin C. The optimal dosage is selected based on the results of complex treatment.

Possible complications

The risk of developing complications in Lynch syndrome depends on the timeliness of treatment. The danger is represented by cases when the tumor process is accompanied by metastasis to the nearest or distant structures.

Lynch syndrome develops:

Crayfish endometrium. The neoplasm is detected in 42-54% of women with Lynch syndrome. The 5-year survival rate for this combination is 82%.
Colorectal cancer. Affects the left intestines. The risk of developing this form of neoplasm in patients reaches 100%.
Crayfish ovaries. The risk of developing a tumor in women with neoplasia in the colon reaches 12%. With early detection of neoplasm, the 5-year survival rate is 58.1%.
Crayfish stomach. It is diagnosed in 5% of cases of Lynch syndrome (the third most common complication).
Crayfish urinary channels. It occurs with Lynch-syndrome. The latter increases the likelihood of developing this type of tumor by 20 times. The risk group includes men aged 50-70 years. The 5-year survival rate is 90%. With invasive forms of neoplasm, this indicator decreases to 60-70%.
Tumor of the thin intestines. It occurs in patients with a genetic predisposition aged 39 years and older. 5-year survival rate in this case reaches 30-35%.
Tumor prostate. A rare complication of Lynch syndrome. Some researchers note that there is no relationship between both forms of cancer.
Head cancer brain. It is diagnosed in 0.3-0.6% of patients with genetic mutations. At the same time, a neoplasm in the brain is detected mainly in persons belonging to this category, at the age of 25-38 years.

Malignant breast tumors in women with genetic mutations are relatively rare. However, patients with a hereditary predisposition over 45 years old are recommended to undergo mammography twice a year in order to diagnose neoplasms early.

With Lynch syndrome, neoplasia may develop in sebaceous glands... In addition, the course of leukemia and other forms of the tumor process is not excluded.

Non-polypous colorectal cancer is a dangerous neoplasm that affects the large intestine. The tumor is characterized by signs of dyspeptic disorders. Treatment for Lynch syndrome involves dynamic monitoring of patients or complete removal large intestine.

Lynch syndrome, or hereditary non-polyposis colorectal cancer, or HNRCCR, is a genetically determined disorder that greatly increases the risk of developing colorectal cancer and some other forms of cancer. According to various sources, it ranges from 3-5% to 9-10% of the total number of colorectal cancer.

The disease is inherited in an autosomal dominant manner. It is caused by damage to chromosomes, often referred to as mutations not associated with sex chromosomes, due to which the risk of passing Lynch syndrome to a child from a father or mother is 50% Colon cancer does not develop in all people with Lynch syndrome, however, it increases the likelihood of developing other types of cancer. For example, if the risk of colon cancer is 80%, then the risk of endometrial cancer is 60%, and the risk of stomach cancer in Lynch syndrome is 15%.

The average age of carriers at the time of the diagnosis of colon cancer is 44 years, the tumor is most often located on the right side. In Lynch syndrome, mutations can occur in some of the genes responsible for DNA replication. And this becomes the reason that DNA does not eliminate the violations, and in connection with their accumulation, cancer develops.

Violations of the genetic code are observed in the genes MLH1, MSH2, MSH6, PMS2. Lynch syndrome can be suspected if a person under the age of 50 has been diagnosed with colon cancer, if there are more than two or more cases of colon cancer in different generations of relatives, or if there are more than two cases of endometrial cancer, cancer in different generations of the family stomach or ovaries. Such individuals are advised to undergo genetic testing, which will help to choose the right tactics both in terms of preventing the development of colon cancer and the frequency of diagnosis.

Lynch syndrome is characterized by an early onset, a high incidence of multiple primary tumors with a predominant lesion of the right colon. In Lynch-II syndrome, colorectal cancer is combined with extraintestinal malignant neoplasms. The diagnosis is made taking into account family history, immunohistochemical tests, colonoscopy, irrigoscopy, biopsy, and other studies. Treatment is operative, combined with chemotherapy.

The identification of the damaged gene will also serve as a reason for conducting research in children and will help them to better protect themselves from the severe consequences of a possible disease.

Dr. Zayatz is a general practitioner, researcher and entrepreneur in the field of biotechnology. He received his PhD in genetics from the University of Cambridge in 2014 and a medical degree from Baylor College of Medicine in 2015.

The number of sources used in this article:. You will find a list of them at the bottom of the page.

Lynch syndrome is also known as hereditary non-polyposis colorectal cancer (NPCR). it hereditary diseasewhich increases the likelihood of developing colon cancer and other cancers. It also increases the risk of developing these cancers at a younger age (under 50). If you think you are at risk, learn how to diagnose Lynch syndrome.

Steps

Recognize the likelihood of developing Lynch syndrome

Establishing diagnosis

Make an appointment with your doctor. If you think you might develop Lynch Syndrome, see a doctor who will refer you to a specialist in genetics (medical genetics). They are experts in genetic screening, counseling and control of genetic diseases such as Lynch syndrome.

See your doctor immediately if you experience any of the above physical symptoms or someone in your family has colon cancer or other cancer.

Determine if you have a genetic predisposition. Your doctor may suspect Lynch Syndrome if someone in your family has colon cancer, uterine cancer, or other cancers, especially if they develop at a young age. Diagnosis is carried out by genetic testing.
- The doctor may ask you about relatives with stomach cancer, small intestine, brain, kidney, liver or ovary, as the gene that mutates into Lynch syndrome increases the risk of several other cancers.
- Your doctor may also ask you if anyone in your family has had cancer in past generations, especially if your family has had cancer for generations.
Get a biopsy of the tumor. If you or your relative has tumors, your doctor can examine them and see if you have Lynch syndrome. He will be able to determine the presence of certain proteins in the tumor that indicate Lynch syndrome.
- If your tumor biopsy is positive, you probably don't have Lynch syndrome. Mutations can only develop in tumors and cancer cells. After a positive result, the doctor may conduct a genetic test to be sure of the absence or presence of Lynch syndrome.
- If someone in your family has had cancer in the past few years, there may be a tissue sample left in the hospital for the doctor to examine.
Get a genetic test. Currently, there are a number of mutations that can occur with Lynch syndrome. This survey looks for mutations in the MLH1, MSH2, MSH6 and EPCAM genes.
- Ask your doctor to send your blood for testing. If you want, donate blood for analysis in several different laboratories.

Lynch syndrome and everything connected with it

Lynch syndrome is a hereditary disorder. Lynch syndrome is a genetically determined disease. The genetic error, which is present in patients with Lynch syndrome, is a group of genes that assign genetic codes to proteins that aid in gene repair.

Learn what a positive result means for Lynch syndrome. If genetic testing confirms the presence of Lynch syndrome, this means that your lifetime risk of cancer is 60-80%. This does not mean that you will definitely have colon cancer or cancer of the uterine body, but only that you are more likely to develop these cancers.

Lynch syndrome is genetic disease autosomal dominant type of inheritance.

Causes of occurrence

One of the most important reasons is the mutation of a gene that is responsible for reparative processes in the unpaired bases of the DNA molecule. Mutations can be of several types and each leads to the formation of cancer in different parts of the colon.

The formation of microsatellite instability occurs, which leads to a violation of the repair in the DNA molecule. Such processes undoubtedly increase the genetic debris that rapidly accumulates in the cell genome. Its accumulation rate is several times higher than that of a healthy person.

Signs of microsatellite tumors in Lynch syndrome

Proximal location;
Mucinous variant;
Low degree of differentiation;
Primary multiple nature of the spread of tumors;

Epidemiology

Non-polypous colorectal canceroccurs in 1 case in 500 patients with various types of colorectal cancer. Thus, its incidence is determined within 2-3% of all episodes of colorectal cancer.

Differences from familial adenomatous polyposis (FAP)

Lynch syndrome manifests itself, in contrast to FAP, with single colorectal adenomas, which do not differ in any way from sudden and accidental tumors.

Clinical criteria for Lynch syndrome

There are three or more close people in the family with confirmed colorectal cancer histologically. Also, if there is or had cancer of the endometrium, ureter, small intestine, renal pelvis. One of the three relatives must be of the first degree of kinship for the other two;
The manifestation of pathology in two generations;
At least one tumor must be identified and diagnosed at the age of fifty.

These criteria are quite strict. Almost half of the families that meet these criteria do not have gene breakdowns. This type of disease is called familial type X colorectal cancer.

In these families, stable microsatellite tumors are formed, in the presence of which the risk of developing colon cancer is quite low.

No one today can justify the appearance of this cancer from the side of heredity and genetics.
Bethesda Guidelines for Diagnosing Lynch Syndrome

The following criteria are used to establish a diagnosis:

Cancer was diagnosed before age 50;
The presence of diseases that are usually associated with Lynch syndrome. It is metachronous cancer;
Patient with colorectal cancer has symptoms of microsatellite instability high degree risk;
The presence of a first-line relative under 50 in a patient with colorectal cancer;

Lynch syndrome symptoms

Colorectal cancer develops with Lynch syndrome as early as 50 years. Then, within 10 years, such patients develop another neoplasm, which is characteristic of this syndrome. Family members also have similar tumors.

If the patient meets most of the above criteria, tests for the presence of microsatellite instability are mandatory. In addition, it will not be superfluous to conduct an immunohistochemical analysis of the tumor.

To facilitate the diagnosis in everyday work, a simple and fairly convenient questionnaire has been developed.

Family-type colorectal cancer risk questionnaire

Evaluation of answers to the questionnaire

For all “no” answers, there is no increased risk of colorectal cancer.

If the answer is “yes” to only 1 question, there is an increased risk of familial colorectal cancer and a standard screening test is mandatory.

If you answer “yes” to one or more questions numbered from 2 to 6, there is a high probability that hereditary form cancer. In this case, it is necessary to undergo a complete genetic examination.

Difficulties in diagnosis

People do not always know the diseases of their relatives and very often families are small in our time, so it is not possible to reliably determine the risk of the disease.

Diagnosing Lynch Syndrome

In order to correctly establish the diagnosis of Lynch syndrome, two stages are necessary:

Microsatellite instability analysis is performed if cancer is suspected in this patient. The technique of polymerase chain reaction is used;
After finding signs of instability, it is necessary to perform a complete genetic analysis for the presence of mutations in the genes. Lynch syndrome is established only through interaction with a geneticist.

Screening diagnostic methods

To prevent the development of colorectal cancer and the formation of metastases, screening diagnostic methods have been developed. Screening is carried out not only for the patient, but also for his family members.

For example, in Germany, screening is used, which includes:

medical checkup;
colonoscopy;
Ultrasound of the abdominal cavity;
Gastroscopy;
Gynecological examination for women, which includes endometrial biopsy and transvaginal ultrasound of the uterus.

Healing activities

Non-polypous colorectal cancer being treated surgical intervention according to international standards. The feasibility of radical surgery has not yet been confirmed by randomized trials, since they have not been conducted.