Random Mutations Play Major Role in Cancer
Posted on by Dr. Francis Collins
We humans are wired to search for a causative agent when something bad happens. When someone develops cancer, we seek a reason. Maybe cancer runs in the family. Or perhaps the person smoked, never wore sunscreen, or drank too much alcohol. At some level, those are reasonable assumptions, as genes, lifestyle, and environment do play important roles in cancer. But a new study claims that the reason why many people get cancer is simply just bad luck.
This bad luck occurs during the normal process of cell division that is essential to helping our bodies grow and remain healthy. Every time a cell divides, its 6 billion letters of DNA are copied, with a new copy going to each daughter cell. Typos inevitably occur during this duplication process, and the cell’s DNA proofreading mechanisms usually catch and correct these typos. However, every once in a while, a typo slips through—and if that misspelling happens to occur in certain key areas of the genome, it can drive a cell onto a pathway of uncontrolled growth that leads to cancer. In fact, according to a team of NIH-funded researchers, nearly two-thirds of DNA typos in human cancers arise in this random way.
The latest findings should help to reassure people being treated for many forms of cancer that they likely couldn’t have prevented their illness. They also serve as an important reminder that, in addition to working on better strategies for prevention, cancer researchers must continue to pursue innovative technologies for early detection and treatment.
Published in the journal Science, this new work comes from Cristian Tomasetti, Lu Li, and Bert Vogelstein of Johns Hopkins University School of Medicine, Baltimore [1]. The team based their findings on mathematical analyses that combined DNA sequencing data, obtained from thousands of tumors and normal tissue samples in The Cancer Genome Atlas, with epidemiological information from the Cancer Research UK, a health charity in the United Kingdom. The analyses allowed the researchers to estimate the proportion of DNA typos in 32 cancer types that could be attributed to heredity, environment, or random DNA copying errors.
Overall, their model indicated 66 percent of cancer mutations result from DNA copying errors. The rest were attributed to environment (29 percent), which includes lifestyle and behavioral factors, and inheritance (5 percent).
It’s important to note that the picture varies considerably among cancers types. Lung cancer, for instance, depends heavily on environmental factors, particularly the damaging effects of smoking. The researchers estimate that 65 percent of lung cancer mutations could be prevented. Still, 35 percent of lung cancer mutations apparently arise from random copying errors, which helps to explain why lung cancer sometimes develops in people who have never smoked.
In other cancers, including prostate, brain, bone, and most childhood cancers, random mutations are estimated to play an even more significant role. The analyses suggest more than 95 percent of mutations causing those forms of cancer occur randomly.
As further evidence for the importance of random copying errors in cancer, the researchers evaluated the incidence, or number of cases, of 17 cancer types from 69 countries around the globe in data collected by the International Agency for Research on Cancer in France. The researchers asked whether differences in the number of times stem cells divide could help to explain differences in the incidence of some common cancers.
In fact, Tomasetti and Vogelstein earlier found a strong correlation between cancer incidence and stem cell divisions in a paper published in 2015 [2]. However, that earlier analysis sparked considerable debate, in part because it lacked data on breast and prostate cancers, two common forms of the disease. It was also limited to people who lived in the United States. The new study, involving people of various nationalities who represented more than half of the world’s population, documents a strong relationship between cancer incidence and normal cell divisions in 17 cancer types, including breast and prostate cancers.
Of course, none of this should dissuade people from pursuing healthier habits to reduce their cancer risk. As the new results suggest, nearly a third of all cancer mutations arise from environmental factors that might be prevented. Because each of us faces the prospect of unavoidable, potentially cancer-causing DNA typos, it’s best to keep any additional errors to a minimum by not smoking, wearing sunscreen, watching your weight, and following other prevention measures.
At the same time, even people who do everything right can still find themselves facing a diagnosis of cancer. To win the battle against this disease, advances in prevention, early detection, and treatment will all be key.
References:
[1] Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention. Tomasetti C, Li L, Vogelstein B. Science. 2017 Mar 24;355(6331):1330-1334.
[2] Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Tomasetti C, Vogelstein B. Science. 2015 Jan 2;347(6217):78-81.
Links:
The Cancer Genome Atlas (NIH)
Bert Vogelstein (Johns Hopkins University School of Medicine, Baltimore)
Cristian Tomasetti (Johns Hopkins University School of Medicine, Baltimore)
NIH Support: National Cancer Institute
“Random Mutations Play Major Role in Cancer”
Mathematical analysis is a language. Metabolomics is the science. NIH funded researchers are asking if language is causative? Circular evidence of mathematical analysis of international tumor registry including Breast and Prostate is wish fulfilling epidemiological evidence for incidence and prevalence but not histological. I would ask the NIH funded researchers to take fingers off the keyboard and put some gloves on and explore metabolomics, morphology, lifestyle.
Further light could be shine on the case of Sickle Cell Disease, a genetic mutation of genes. What now? Is Sickle Cell causation more about environmental cause or more in the camp of random mutation of gene during cell division or copying of the gene during cell division; spur on by pre selections of some cause determined a head of time like environment. OR is this disease both environmental and genetic mutation. The question then become the chicken or the egg game, which come first in different environments.
Preventatists tend to agree with the findings here, but relate it all to the fact that the success of human evolution has depended upon each body knowing precisely how to organise the billions of strands of intelligence and communication needed to keep the individual functioning. HOWEVER — introduce stress, and things go haywire….simply because of the requirement of each body to defend itself, at all costs. Preventatism addresses this problem simply and effectively, and one day will be recognised for its efficiency and ability to maintain health. Theses things were thought out and developed 4 or 5 decades ago, and have been used with success in treating stress-related disorders, and helping those who are healthy, maintaining that status quo.
Mutation randomness (caused by the stochastic nature of the chemical reactions) makes senseless the search for cancer gene biomarkers. Besides, in each person, alteration of a “biomarker” is accompanied by the regulation of hundreds other genes and millions of point mutations, in a never repeatable combination. Although neglected by most authors, the contribution of the other alterations is not negligible and no meta-analysis can account for each possible combination in a really stratified population as race, sex, age, environment, medical history etc. (Iacobas, The Genomic Fabric Perspective on the Transcriptome between Universal Quantifiers and Personalized Genomic Medicine. Biological Theory, 2016, 11(3): 123-137. Moreover, as selected from the most frequently altered genes in a large population, the biomarkers are less protected by the homestatic mechanisms, like minor players. As such, they have little therapeutic value, their restoration lacking significant curative potential. Therefore, we have developed a personalized procedure to identify for each cancer patient the Gene Master Regulators (GMRs), whose highly protected expression modulates most major functional pathways. As validated (p-val = 0,000152) for thyroid cancer (manuscripts in preparation), “smart” manipulation of GMRs selectively destroys the cancer nodules with minimal effects on the surrounding normal tissue.
Great article. Thanks for sharing this.
” a new study claims that the reason why many people get cancer is simply just bad luck.” Looking at it from this perspective is scary.
Indeed the existentialist philosophers were correct with the whole talk of “been qualified to die the very day we are born”