The role of genetics and heredity in the development of cancer

"The term "cancer family" is associated with Napoleon"

Newspaper.RuPeople with a family history of cancers should check their health regularly:

so you can identify and cure the disease at an early stage. Professor Larisa Akulenko, Head of the Department of Medical Genetics of the Moscow State Medical and Dental University, tells about the mechanism of development of hereditary cancers, the possibilities of medicine in the fight against them and the latest genetic developments in this area.

– The term "cancer family" is sometimes found in the literature. Please expand it in more detail.
– This term is associated with Napoleon Bonaparte. For the first time the term "cancer family" was introduced in 1913 by the scientist Vartin. He first described a family (namely the Bonaparte family), where there were many cancers of the gastrointestinal tract: for many generations, the ancestors and descendants of the French emperor died from cancer of the gastrointestinal tract, mainly the stomach. By the way, they have become a classic example of the "cancer family", having been included as an example in all textbooks on oncogenetics. Now the term is practically not used, instead they talk about "family cancer".

– The term "cancer family" refers only to cancer of the gastrointestinal tract?
– Not at all. It was just the first described family – the Napoleon family, which suffered from gastrointestinal cancer. After that, a large number of cancer families with tumors of different localizations were described in the literature, for example, ovarian and breast cancers in the 1930s and 1950s. Descriptive cases eventually prompted in the 1970s to conduct special studies aimed at studying the role of genetic factors in the development of cancer, mainly in the United States. Thousands of pedigrees were studied: patients with a particular form of cancer were interviewed, clinical-genealogical and population-statistical methods were used. These works received similar data: cancer in the families of patients is 3-6 times more common than would be expected based on the population frequency. This is how stomach cancer and breast cancer were studied. Then the question arose whether cancer is contagious. To find out, we used a different approach – we studied the incidence of cancer among relatives and the frequency among spouses. It was shown that the frequency is higher among relatives, and the spouses correspond to the population (these studies were conducted mainly on the example of lung cancer). Thus, the assumption that cancer is contagious was completely rejected.

– How many people among the closest relatives must have cancer in order to be able to talk about a "cancer family"?
– Two or more relatives of the first degree of kinship (these are parents, children, sisters, brothers). According to the so–called Amsterdam criterion, there are three or more cases of cancer of the same localization in the family. There may be much more cases of cancer among relatives of the second and further degree of kinship.

– How does a hereditary mutation that causes cancer work?
– Let's start with the basics. The human genome consists of 23 pairs of chromosomes – one from the father, one from the mother. When a person receives a gene mutation, it gets to him either from his father or from his mother (at the same time it is extremely rare). That is, the gene has two manifestations, two alleles – one healthy and the other cancerous. A healthy allele will compensate for the function of producing a protein product (enzyme or hormone) that encodes this gene for a certain time. The tumor will not develop in this case. In order for the initiation of carcinogenesis to begin, another mutation must occur – a healthy allele in a somatic cell.

This theory is called the double impact theory. It was put forward by Alfrend Knudson back in 1971. Ten years later, it was confirmed in an experiment, and all our knowledge is now based on it. When a mutation of one allele already exists, the gene becomes brittle, vulnerable. And given that we are constantly in the environment of carcinogens, this mutation can easily occur. Then carcinogenesis begins, but it is reversible in the first and second stages. The third, fourth and fifth stages (not cancer, but carcinogenesis, the genetic mechanism) are already irreversible. Cancer begins with a single cell, which then gives clones. However, all cells carry a predisposition, so the probability of a mutation in another cell is not so small. It should be noted that the body also has mechanisms of repair, repair. True, predisposition genes are sometimes also genes responsible for repair. That is, the body cannot fight against cancers, since its repair system does not work genetically correctly.

– What methods are being developed by geneticists in order to prevent the disease? Can we say that the future belongs to genetic engineering?
– If we talk about treatment, then the future really belongs to genetic engineering. But this is a distant future. However, cancer should not be confused with genetic diseases caused by genome defects, such as hemophilia. Cancer is not a monogenic disease. Cancer is not inherited – only predisposition is transmitted. Cancer is still not a disease of the genome, but a disease of somatic cells.

Mutations that cause predisposition are inherited. But in order for this predisposition to cancer to develop a disease, a long way must be traveled. If we are talking about a hereditary predisposition to cancer, we must first establish it using, for example, DNA diagnostics. There are other methods – clinical and genealogical, which were mentioned above; syndromological, since there are a number of syndromes that manifest themselves in the development of cancer. For a number of cases, the gene in which the mutation is responsible for the occurrence of the disease can be studied by a fairly cheap PCR polymerase chain reaction method. But in some cases there is a picture of familial cancer, and known mutations are not detected. Then they resort to more precise methods – sequencing of all coding sequences. This is a very accurate, but very expensive method. Now there are methods of biochips with which you can read almost the entire human genome very quickly, however, unfortunately, these methods have not yet been widely implemented.

– How regularly does a person need to be examined in order to detect cancer at an early stage and take action? Once every six months – is that enough?
– When we talk about cancer prevention, there is a concept of complex, secondary and tertiary prevention. Primary prevention is the elimination of all factors that increase the risk of developing cancer. However, since we are talking, for example, about ecology, these factors are not always subject to doctors. If a person has a hereditary predisposition to cancer, we are talking about secondary prevention, which includes both early diagnosis of cancer and its prevention. Cancer treatment in the early stages is successful – people may well not die from it. It should be borne in mind that hereditary cancer, as a rule, occurs earlier than non-hereditary. It tends to manifest itself in primary multiple lesions of different organs and in the defeat of paired organs (mammary gland, ovaries, kidneys). Since a mutation in a gene that carries a predisposition to cancer does not occur during life, but comes from the very first cell of the human body – the zygote, hereditary cancer manifests early.

In early diagnosis, we distinguish groups by age (not counting childhood tumors: we are not talking about them now). The first group is young, from 18 to 35 years old. 35 years is the peak of the manifestation of hereditary cancer. The second group is from 35 to 55 years old. As a rule, if people do not undergo preventive measures, hereditary cancer should manifest itself before the age of 55. For people with a predisposition to each type of cancer, there are so-called gold standards of primary examination for early diagnosis. For example, in the prevention of cancer of the female reproductive system, examination of specialized doctors (gynecologist, mammologist), ultrasound of the pelvic organs and breast, mammography (it should be started from the age of 25), tumor markers are shown. Young women (under 35 years old) this is done once a year, older – twice a year. Naturally, if any pathologies are detected, the examination is expanded until the diagnosis is established. Then you need to treat this pathology. This is prevention in this case – the elimination of dangerous precancerous conditions and the improvement of the body's natural resistance. There are drugs aimed at increasing the expression of a healthy allele (type) of the gene that is responsible for hereditary predisposition to a certain type of cancer.

– And what is the difference between preventive cancer treatment methods in Russia and abroad?
– Preventive mastectomy and ovariectomy – removal of the breast and ovaries - are practiced abroad as a cancer prevention measure. We do not have a legal basis for such operations yet: the Ministry of Health does not allow this.

There are no other significant features. However, preventive studies for the general population, especially in the regions, are not always available. A lot of important methods – tested and approved – have not been introduced into medical practice. DNA diagnostics laboratories are not available everywhere, and the staff is not trained in the genetic aspect of cancer prevention. The big problem is not the equipment, but the personnel. But this is a solvable problem.

Portal "Eternal youth" http://vechnayamolodost.ru
28.03.2012