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Why some cancers seems to develop in an instant - cells can explode wreaking havoc in DNA By Fiona Macrae
The mystery of 'instant cancers' - tumours that seem to appear out of nowhere - has been solved by British scientists.
In some cases, a single apocalyptic ‘explosion’ in a cell can cause as much damage to the DNA as decades of hard living.
A model of a DNA Molecule. Scientists have found one in 40 cancers could develop rapidly after an unexpected cell explosion causes DNA damage
The finding, from the Wellcome Trust Sanger Institute near Cambridge, contradicts the long-held theory that cancer is the consequence of hundreds, or thousands, of mutations that build up over a person’s lifetime.
It suggests that no matter how healthy some people try to be, fates is conspiring against them. And it helps explain why some people are diagnosed with cancer only months after x-rays or other tests found no trace of the disease.
The discovery was made from the study of the genetic flaws in 750 tumours.
In most cases, the damage seen to the chromosomes fitted with the conventional picture of cancer creeping up over many years.
But at least one tumour in 40 didn’t fit the standard pattern, the journal Cell reports.
Instead, the damage appeared to have been done almost overnight.
Researcher Dr Peter Campbell said: ‘The results astounded us. It seems that in a single cell, in a single event, one or more of the chromosomes explode - literally into hundreds of fragments.’
If the cell then botches the repair, stitching the fragments back together in a ‘higgledy piggledy’ fashion, the damage to its genome, or cache of DNA, leaves it ripe for the rapid development of cancer.
Dr Campbell said: ‘The cell should say “that’s it”, and give up, but instead it tried to piece the chromosomes back together like a valuable piece of porcelain.
‘They attempt to reconstruct the unreconstructable and they wind up with a disastrous genome that shortens the road to cancer.’
The phenomenon is particularly common in bone cancers, where the distinct pattern of damage is seen in up to one in four cases. But it thought to be to blame for more than one in 40 of all cases of the disease.
Dr Campbell said: ‘Many cancers will take years, decades, to develop. But we also know that in some patients cancers seem to appear much more quickly than that.
'We have examples of people who had a totally normal mammogram or other x-ray and within a few months they develop a nasty aggressive cancer and it may be that a single catastrophic event shortened the development.’
The researchers aren’t sure what triggers such the catastrophic damage behind ‘instant cancers’ but possible culprits include x-rays and sunburn.
Dr Campbell said: ‘If we can understand its roots, we may learn how to prevent that kind of cancer happening.’
The study is part of a landmark project to chart the genetic flaws in dozens of types of cancer.
In future, every patient could have their own 'mutation chart', mapping the precise flaws behind their illness and indicating the best drugs to treat them.
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Radiation and Cancer Risks: Is it safe to have X-Rays?
Article Authored by: Robert H. Wagner, MD, FACNP
The association between cancer and radiation is a well-documented one and has led to fear and anxiety among patients who are supposed to receive diagnostic radiology studies. Shortly after the discovery of x-rays by Wilhelm Roentgen in 1895, and radioactivity by Henri Bequerel the following year, radiation became the wonder of the new century. The following decades would see radiation used as an elixir of health, a tool to measure shoe sizes, a diagnostic and therapeutic tool in medicine, a means to produce electricity, and a devastating weapon of war. Initially thought to be safe, it was later discovered that radiation had the potential to cause cancer. The initial enthusiasm for radiation slowly turned to fear. The entertainment industry produced many films on the unknown mutating effects of radiation on living creatures. Even today, popular television will use radiation in less than accurate ways to create an aura of excitement. These stories promote misconceptions about radioactivity and lead to misunderstanding by the general public. Despite all of the myth and mystery that surrounds radiation, the fact remains that radiation is the best-studied carcinogen known to mankind.
When discussing radiation carcinogenesis it is important to understand several concepts first. The first is that there are two broad categories of effects, those that occur directly as a result of radiation exposure and those that occur on a statistical basis. For example, exposing a person to approximately 100 rads of radiation (0.1 Gray) or the equivalent of 100 CT scans to the total body results in a slight decrease in the circulating white cells and platelets. This will happen in everyone exposed to this dose. The induction of cancer or genetic abnormalities occurs in a percentage of those exposed to a certain dose of radiation. The Biologic Effects of Ionizing Radiation report (BEIR V) states that if 100,000 people are exposed to 10 rads of radiation, then there will be 800 additional cancers in that population above the normally occurring amount. Thus, you have a statistically increased chance of developing a cancer.
Doses and dose rates are also important considerations. Sit out in the Caribbean sun without any sun block for two hours and you’re likely to get sunburn. Sit in the same sunlight for two minutes a day for 60 days, and you probably won’t even develop a tan. In both cases, you’ve spent a total of 120 minutes in the sun. The difference is that when you extend the exposure, there is some healing of the damage over time. The same is true for radiation damage. Fifteen rads (0.15 Gray) given all at once will temporarily decrease the number of sperm cells that are being produced. Extend that exposure over a period of weeks or months, and you won’t see those changes.
Cancer may be caused by damage to the DNA. DNA damage occurs on a regular basis even without the presence of radiation, and may be the reason that one out of four people will develop a cancer of some kind. Normal cells have mechanisms that repair this genetic damage. If the damage is not identified or if the rate of damage is too high for the repair mechanisms, it may result in a cancer being formed. Thus, there is a definite link with high dose radiation and cancer. Cancers caused by radiation are biologically the same when compared with cancers that occur naturally. Under a microscope, there is no difference from a thyroid cancer that occurs spontaneously and a thyroid cancer caused by radiation. Although large doses of radiation are known to cause cancer, what happens at the small diagnostic doses that are used in medicine is still unknown. There are several theories that attempt to describe the effects of low-level radiation.
Most radiation safety models make the assumption that there is no safe dose of radiation and even the tiniest amount increases your risk for cancer. If you expose one million people to 1 rad of radiation, you will expect to see 800 additional cancers during their lifetime. By extrapolation, exposing the same million people to 10 millirads of radiation (a chest x-ray) you will expect to see 8 additional cancers over their lifetime. Statistically however 250,000 of that million people will get cancer anyway. The difference of a chest x-ray to a million people in causing cancer (250,000 vs. 250,008) is impossible to measure. Many people disagree with this model since it does not take into account normal cellular repair of genetic damage.
A recently advanced theory is one called hormesis. It makes the assumption that the additional radiation given at lower doses does cause some genetic damage, but also stimulates the cells to fix the naturally occurring genetic damage at an earlier stage. A naturally occurring DNA abnormality that might later lead to development of a cancer could be repaired because the additional radiation damage triggered the repair mechanism. The result is that this theory makes the claim that there are actually fewer cancers when people are exposed to small amounts of radiation. While it may be difficult to believe that a small amount of radiation may be healthy for you, there are a growing number of scientists and studies to support this claim.
All of the diagnostic studies performed in your radiology or nuclear medicine department fall into this low-level radiation group. The risk of developing a cancer from any of these studies is very small, but the benefit can be significant. There is no question that mammography identifies breast cancers at an early stage and therefore improves the chance of survival. The small number of cancers that might be caused by the mammogram is far overwhelmed by the number of cancers that are detected at an early stage. On the other hand, performing a total body CT scan for screening purposes only is not justified. The important thing to consider is the risk versus the benefit of the study.
In conclusion, radiation does indeed have the potential to cause cancer at larger doses, but the effects of smaller doses such as those used in diagnostic medicine are still unknown. If it does cause cancer at these low doses, the overall risk is very small, especially when compared to the potential benefit of improving the diagnosis and treatment of many different diseases.
Robert H. Wagner, M.D. Associate Professor of Radiology Loyola University Medical Center
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