Cellular inheritance: how to identify a predisposition to cancer
About 4 million Russians have cancer, according to medical experts, noting that genetic causes are not the least among the causes of cancer. The presence of relatives with certain types of cancer does not guarantee, but increases the chances of the same disease in offspring, scientists believe. Protect yourself from their occurrence can genetic analysis of predisposition to a particular type of cancer, but a hundred percent accuracy it does not guarantee. Details - in the material "Izvestia".
Millions of patients
The number of cancer patients in Russia is growing and already exceeds 4 million people, according to the Russian Center for Information Technology and Epidemiological Research in Oncology as part of the Herzen MNIOI. Last year, according to this organization, 674,587 cases of malignant neoplasms were detected (including 307,909 and 366,678 in male and female patients, respectively), which is 8 and 7.7% higher than in 2022, respectively, and 22.8% higher than a decade ago.
Oncologists and scientists interviewed by Izvestia, based on their own practice, note that malignant neoplasms are multifactorial, that is, they arise during life from a combination of genetic and external causes, such as background stress, general poor nutrition, and unfavorable environmental conditions.
- People are most affected by cancers of the breast, large intestine, lung or brain. The starting point of the disease is considered to be the process of uncontrolled division of malignant cells, which then penetrate into other tissues and organs with blood, forming metastases, - says oncologist, Doctor of Medical Sciences, Professor, Honored Doctor of the Russian Federation Nikolay Ognerubov.
In the vast majority of cases, the development of a malignant tumor occurs spontaneously. This type of cancer is called sporadic, or random, as all genetic mutations that can be detected, accumulated during life and predict their appearance with accuracy to the day is impossible. In general, all cancers have some degree of heredity in one way or another, so it is important for oncologists to collect a cancer history regarding relatives. Non-hereditary cancer occurs mainly in adulthood or old age as a result of accumulation of cell damage in various genes, including genes that regulate the cell cycle, somatic mutations, and tumorigenesis, scientists believe.
- There are the following signs and prerequisites for the development of an inherited form of cancer, confirming the presence of a family history of cancer. This is an early manifestation of the disease, that is, its manifestation at a young or even in childhood, synchronous and metachronous occurrence of several tumor foci in paired organs of the human body and features of tumor morphology, - says candidate of medical sciences, associate professor, pathologist of the highest qualification category, scientist, leading expert in the field of oncomorphology and clinical pathology of tumors Research Institute of Human Morphology named after Acad. A.P. Avtsyn Maxim Mnihovich.
Another sign of hereditary tumor is the rejuvenation of cancer in subsequent generations.
- On average, the rejuvenation of oncology occurs for 10 years, starting from the age of the earliest manifestation of the disease - says senior researcher, physician-geneticist of the polyclinic department of the NMIC Oncology named after N.N. Blokhin. N.N. Blokhin, Candidate of Medical Sciences Margarita Filippova.
Crocodile genes
At the molecular level, the "portrait" of cancer looks like this. The DNA of the nucleus of the human body contains all biological information necessary for the creation and functioning of cells, organs and systems, and all hereditary material is represented by 23 pairs of chromosomes - 22 pairs of autosomes and a pair of sex chromosomes. DNA is a long polymeric molecule consisting of a sequence of repeating units - nucleotides. And the sequence of nucleotides "encodes" information about different types of RNA, necessary for the subsequent biosynthesis of essential proteins. Malignant transformation is caused by mutations that disrupt the balance of cell division and death. It is known that at least 5-9 mutations in different oncogenes and antioncogenes are necessary for the emergence of a transformed cell clone, i.e. a cancer cell.
- The growth of a malignant neoplasm begins with tumorigenic transformation of normal cells when cellular DNA is irreversibly damaged. Mutations that cause tumor growth affect genes involved in the processes of cell division and cell death. The following four classes of genes are commonly damaged. These are genes encoding the synthesis of growth factors and their receptors, as well as signaling proteins involved in various stages of the cell division process (including cellular oncogenes). Genes regulating apoptosis, genes from the cancer suppressor family, and DNA repair enzyme genes. Each of them can be a starting point for the development of hereditary cancer," Maksim Mnihovich continues.
Of human malignant neoplasms in subsequent generations can manifest no more than 10-15% of diseases associated with germinal, that is, congenital, mutations, say scientists from the N.N. Blokhin Research Center of Oncology. N.N. Blokhin Oncology Center.
- In some nosologies, this percentage may be 20 and 30%. Women are more prone to hereditary cancer, because among hereditary diseases prevail breast cancer, colon cancer, breast cancer and ovarian cancer, - says Margarita Filippova.
Responsible for the emergence of a particular tumor is a special gene, say scientists from the Research Institute of Human Morphology named after Acad. A.P. Avtsyn. For example, retinal cancer in children, retinoblastoma, arises due to mutation of the so-called RB1 gene, kidney cancer in children, or nephroblastoma, arises due to mutation of the WT1 gene. Familial breast and ovarian cancer occurs due to mutation of BRCA1, BRCA2 genes. Familial adenomatous polyposis occurs due to APC gene mutation. Medullary thyroid cancer occurs due to mutation of the RET gene. Hereditary syndromes are three times more likely to cause these cancers, scientists say.
- For example, in hereditary colon polyposis, if a patient does not undergo a hemicolectomy, the cancer will develop at 100 percent. With RB1 mutation, patients develop retinoblastomas, and if the child survives them, then the risk of osteosarcoma and melanoma is high (reaches up to 90%)," says Maxim Mnihovich.
Inaccurate prognosis
- Familial cancer describes the situation when within one family there is an increased, compared to the population, frequency of any one or more types of tumors. But there are types of cancer that are not inherited. We are talking about lung cancer, for example, or skin cancer such as basaloma," says Nikolai Ognerubov.
No one can protect themselves from cancer one hundred percent, but anyone can assess the degree of personal predisposition to this or that cancer. The assessment is given only after molecular genetic DNA testing on the basis of blood leukocytes. Detection of pathogenic mutation in the nucleus of human cells is carried out in laboratory conditions in major cancer centers in Russia. However, only those who have already been diagnosed with cancer can undergo it at the expense of the MHI program.
- In this case, this information can help doctors diagnose and select targeted therapy faster and more accurately," says Margarita Filippova, MD, PhD, from the N.N. Blokhin Oncology Center. N.N. Blokhin.
However, as doctors assure, this molecular study does not guarantee information about the hundred percent occurrence of a particular type of cancer in a person.
- Detection of a pathogenic germinal mutation in the DNA of a healthy individual does not allow to determine the hundred percent occurrence of a certain type of hereditary cancer with a hundred percent accuracy, but only the predisposition. We detect the presence of mutations in a person, and the realization of this mutation depends on individual living conditions, hormonal factors and other prerequisites, - continues Margarita Filippova.
There is no single mutation that has a hundred percent risk of causing a particular type of cancer. However, you should listen to doctors' recommendations and be attentive to your own health, doctors say.
- If possible, you should study the history of oncology in your family members, if there are two or more cases of the same disease, you should be examined by a specialized specialist and consult an oncologist. It is necessary to take tests for oncomarkers and lead a healthy lifestyle. As a rule, cancer mutations carry a high risk of 50% or 60%, but the risk is never absolute. But it is worth finding out what kind of cancer you personally have a predisposition to," summarizes Nikolay Ognerubov.
