Release date: 2017-03-28
Why is a person suffering from cancer? Because there is a small cell in his body that grows wildly in an uncontrolled manner. Why are these cells out of control? Because they have mutated, the accumulation of multiple mutations eventually leads to normal cells becoming cancer cells. But where did these mutations come from?
For this, the scientific community has always said that cancer is "bad luck" because mutations in stem cells are accidental, but other scientists believe that environmental carcinogens play a more important role in cancer production. This inconsistency is mainly due to the use of different mathematical models to study existing human cancer and stem cell data, so it is difficult to sort out the effects of a single factor.
Scientists at the Johns Hopkins Kimmel Cancer Center recently reported a new study showing that nearly two-thirds of the causes of cancer mutations are due to random, unpredictable DNA replication "errors" that were established Based on a new mathematical model based on DNA sequencing and epidemiological data from around the world .
The research was published in the March 23 issue of Science.
Cancer "bad luck" vs. environmental and genetic factors
The author of the article, Dr. Cristian Tomasetti, assistant professor of biostatistics at Johns Hopkins University, said, "We all know that we must avoid environmental factors such as smoking, which can reduce our cancer risk, but each normal cell divides each time. Replicating its DNA to produce two new cells, which causes multiple errors, we don't know much about this. These replication errors are an important source of cancer mutations, and their importance has been underestimated. And this new study raises these The first estimate of the proportion of errors that caused mutations."
The researchers point out that their conclusion is consistent with epidemiological findings: about 40% of cancers can be prevented by avoiding unhealthy environments and lifestyles. But one of the factors driving this new study is that people who follow the rules of healthy living, who are not smokers, eat very healthy, maintain a healthy weight, have little or no exposure to known carcinogens, and have no family. A history of illness, so why do they get cancer? Cancer Research Bulls' Latest "Nature": New Combination Cancer Immunotherapy
Tomasetti they think the answer to this question lies in random DNA replication errors. They point out that factors that reduce known and unknown environmental risks can have a major impact on cancer incidence. But the new study confirms that if the early detection diagnosis is ignored, there will also be a large number of cancers caused by random DNA replication errors.
"No matter how perfect the environment is, these cancers will still happen," said Bert Vogelstein, author of the Ludwig Cancer Research Center.
Tomasetti and Vogelstein et al. published a paper in Science in 2015, pointing out that people are suffering from cancer because of "bad luck" rather than genetic and environmental factors.
They analyzed data on 31 human tissue carcinogenesis and found that 22 of these cancers can be explained by "poor luck" in stem cell division, including pancreatic cancer, bone cancer, ovarian cancer, and brain cancer. Studies have shown that the correlation between the number of normal stem cells in human tissue and the incidence of cancer in the tissue is 0.804, which is highly correlated. According to a new statistical model developed by the researchers, the cancer incidence rate of the tissue is the square of this correlation, expressed as a percentage in the form of 65%.
Proportion of various cancers
This explains why certain cancers in the United States (such as colon cancer) occur more often than other cancers (such as brain cancer), and recent research raises a different question: how many cancer mutations are caused by these DNA replication errors. high?
To answer this question, the researchers carefully analyzed mutations in 32 cancer types that caused abnormal cell growth. They developed a new mathematical model using DNA sequencing data from the Cancer Genome Atlas and epidemiological data from the UK Cancer Research Database.
The researchers point out that it usually takes more than two key genetic mutations to trigger cancer. In a single human body, these mutations occur due to random DNA replication errors, environmental or genetic genes, and Tomasetti and Vogelstein use their mathematical models to arrive at some conclusions, such as when key mutations in pancreatic cancer occur simultaneously. Of these, 77% are due to random DNA replication errors, 18% are environmental factors, such as smoking, and the remaining 5% are hereditary.
In other cancer types, such as prostate cancer, brain cancer or bone cancer, more than 95% of the mutations are due to random replication errors.
They noticed that lung cancer is different - 65% of mutations are due to environmental factors, mainly smoking, and 35% are due to DNA replication errors. It is unclear whether genetic factors play a role in lung cancer.
By analyzing these 32 cancer types, the researchers estimated that 66% of cancer mutations were caused by replication errors, 29% were attributable to lifestyle or environmental factors, and the remaining 5% were inherited.
Tomasetti and Vogelstein's 2015 research paper sparked fierce debates in the scientific community. Some scholars believe that their previous papers did not include breast cancer or prostate cancer, only reflecting the incidence of cancer in the United States.
In the latest paper, Tomasetti and Vogelstein report the results of the analysis worldwide and get a similar model to support their previous conclusions. They believe that the more cells divide, the higher the probability of DNA replication in organ cells . The researchers compared the total number of stem cell divisions with cancer incidence data collected by the International Agency for Research on Cancer, which included data on 423 cancer patients from 68 countries outside the United States. This time the researchers analyzed data on breast and prostate cancer. They found that there is a strong correlation between the incidence of cancer in 17 cancer types and normal cell division, regardless of the country's environment or stage of economic development. Science breakthrough study: how smoking causes cancer
Tomasetti said that as the social population ages, these random DNA replication errors will become more and more important. And because these errors cause a large percentage of cancer, people with cancer have avoided known risk factors, which may also be partial compensation. "It's not your fault," Vogelstein said. "What you have done or not done will not affect your illness."
Source: Biopass
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