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Most cancer mutations are 'just bad luck'

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Metastatic melanoma cells										NIH

Unfortunately, primary prevention is not possible for those cancers that are caused by random errors, which is why to avoid cancers altogether, "we need to focus more on early detection", Tomasetti said.

The research, published in the journal Science, indicates that nearly two-thirds of cancer-causing mutations are due to DNA copying errors.

Most mutations that cause cancer result from random DNA copying errors that occur when cells divide. For prostate cancer, the researchers calculated that 95 percent of the mutations driving the disease were random.

Vogelstein and Tomasetti said that their team's analyses call attention to a critical part of cancer etiology-presumably non-preventable random DNA copying errors, which are not often discussed.

"Occasionally they occur in a cancer driver gene".

The study also shines a spotlight on cancers that will occur no matter how flawless the environment, and may alleviate the guilt some patients face when they are diagnosed.

However many people still develop cancer for no obvious reason and even though they follow all the rules of healthy living - nonsmoker, healthy diet, healthy weight, little or no exposure to known carcinogens and and have no family history of the disease.

The scientists used a mathematical model that analysed genome sequencing and epidemiological data for 32 types of cancer.

Though we can't predict how random mutations will cause cancer, knowing what we don't know is a marked improvement from swimming in unknown unknowns.

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Overall, they found, about two-thirds of the difference in cancer rates from one kind of tissue to another is due to differences in the rates of cell division in those tissues.

"Despite the role of the random replication component in producing mutations, you could still reduce the cancer risk hugely, for many types of cancer, by getting rid of the environmental and/or hereditary causes", he said. Thus, random replication errors alone cause cancer in only 10 percent of adenocarcinoma patients, while the other 90 percent require smoking, second hand smoke, or some other environmental exposure as well.

Meaning, cancer can take place no matter how flawless the environment is.

In a theoretical example, in which the environment greatly increased the incidence of cancer, the team showed that around 40 percent of cancer-associated mutations would still be due to DNA replication errors. That's important, because statisticians have shaken their heads when journalists interpreted the researchers' previous study to mean that a large proportion of cancers are just "bad luck".

The authors of the study published Thursday poked a hornet's nest by suggesting that many cancers are unavoidable.

In contrast, they noted, more than two-thirds of the mutations in lung cancer arise from environmental factors, mostly smoking.

"It is a combination of these three factors - so you can some degree of prevention of cancer by modifying these lifestyle or environmental factors", said Professor William Gallagher, Director Irish Cancer Society BREAST-PREDICT Centre and UCD Convway Institute. This could help explain why different tissue types do have different risks of cancer. For example, environmental factors, primarily smoking, caused 65 percent of all lung cancers in the study, the researchers found. Cells of the small intestine divide rarely, and only 0.2 percent of people develop cancer there.

To attribute so many cancer mutations to chance seems to negate public health messages, Waclaw says, and some people may find the calculation that 66 percent of cancer-associated mutations are unavoidable disturbing because they spend a lot of time trying to prevent cancer.

Dr Vogelstein says this research highlights an urgent need for new methods to detect all cancers - the ones that can't be prevented - earlier while they're still curable. "We now know as a result of this research that most of the enemies [in the war on cancer] are inside us". For example, although it may be possible to estimate how much smoking contributed to someone's lung cancer, it would be more hard to fully capture the impact of air pollution or exposure to radon, he says.

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