American scientists have found that some types of cancer are nearly impossible to prevent. The mutations that cause them are less dependent on environmental factors and more on errors in DNA copying during stem cell division. "Lenta.ru" tells in more detail about the new study published in the journal Science.
Cancer is the result of a gradual accumulation of mutations that contribute to uncontrolled cell proliferation and the formation of tumors. What causes these mutations? There are external and internal factors. External - this is smoking, unhealthy diet, exposure to ultraviolet radiation, a sedentary lifestyle. So, the sun's rays can damage the DNA of melanocytes, which leads to the development of melanoma. The influence of external factors can be weakened, and this is what is called primary cancer prevention. But mutations can be inherited. In addition, they arise from errors in DNA copying during cell division.
Previously, scientists from Johns Hopkins University suggested that errors in DNA copying may be the reason that cancers are more likely to occur in some tissues and organs than in others. This hypothesis was based on the fact that in the United States, the risk of developing cancer throughout life in certain types of tissues is strongly correlated with the total number of divisions of normal stem cells in these tissues.
Each time a stem cell divides, there are approximately three mutations in its DNA. Naturally, sooner or later, the changes will affect the genes associated with cancer. The more often a cell divides, the greater the risk. Scientists can estimate the relative risk of malignant tumors forming in different organs. Determining the contribution of each of the three sources of mutation (environment, inheritance, and division) to cancer is more challenging.
In some cancer patients, heredity and division is sufficient for the development of the disease, in others, some mutations were inherited (they can be called H-mutations), others - endogenous - appeared during DNA copying (R-mutations), and the rest are the result of external factors (E -mutation). All this greatly complicates the overall picture, but the researchers still found a way to assess the contribution of all three sources. They reasonably assumed that R-mutations are evenly distributed among all people of a given age. At the same time, hereditary and environmental factors can vary widely and affect each person in different ways.
Photo: Ed Uthman, MD / Wikimedia
Scientists analyzed cancer cases in 69 countries, covering the environmental conditions in which a total of 4.8 billion people live. Disease data were obtained from the archives of the International Agency for Research on Cancer (IARC). It turned out that for all countries there is a clear correlation between the number of stem cell divisions and the risk of cancer. And the older the age, the stronger this correlation.
How to determine the contribution to mutations of each of the three groups of factors? Imagine that all the people of the Earth had hereditary mutations corrected and all of humanity was relocated to the planet "B" with ideal environmental conditions. This means that on this planet, E and H are equal to zero, and all mutations occur due to errors in copying DNA during stem cell division. Unfortunately, R is always greater than zero, since there is no perfect mechanism for copying genes. Although we must not forget that replication errors provide an evolutionary process, and ultra-precise copying of genes would exclude human existence.
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Suppose that a powerful mutagen was sprayed into the biosphere of planet "B" that affected all habitats. All people would be equally likely to be affected by this factor throughout their lives. Suppose a mutagen increases the rate of accumulation of somatic mutations in stem cells, as a result, the likelihood of cancer increases 10 times. In other words, 90 percent of all malignant tumors arise from exposure to the environment, and they can be prevented by avoiding contact with the mutagen.
Suppose that three driver mutations are enough for cancer to occur. 10 percent of diseases thus develop due to the fact that all three mutations are associated with errors in replication. The rest are a consequence of various combinations of E- and R-mutations. The share of all driver R-mutations in the population of planet "B" will be 40 percent, and this indicator cannot be reduced in any way.
This theoretical example does not differ much from the situation that developed with lung adenocarcinoma. This type of cancer is 90 percent avoidable by avoiding exposure to tobacco smoke. However, it has not been proven that the predisposition to adenocarcinoma is inherited. To find out what proportion of driver R mutations are responsible for this type of cancer, the researchers analyzed the results of epidemiological studies and information about DNA sequences. More than a third (35 percent) of cancer-related mutations, it turned out, are due to copy errors.
Pancreatic duct cancer is preventable in only 37 percent of cases (77 percent of R-mutations, 18 percent of E-mutations). Tumors of the head, prostate, and bone are most common from somatic driver mutations and are nearly impossible to prevent with lifestyle changes, unlike lung, skin, or esophageal cancers. Overall, it is estimated that 42 percent of all cancers can be avoided by eliminating environmental influences.
As a result of an aging population, cancer is becoming the leading cause of death in the world. Primary prevention, according to experts, is the best way to reduce mortality. However, not all types of malignant tumors can be protected by minimizing the negative impact of external factors. In this case, secondary prevention is necessary, that is, early medical intervention.
Alexander Enikeev