Cancer down to bad luck more than lifestyle or genes

Most cases of cancer are the result of sheer bad luck rather than unhealthy lifestyles, diet or even inherited genes, new research suggests.

Random mutations that occur in DNA when cells divide are responsible for two thirds of adult cancers across a wide range of tissues, a study has shown.

The remaining third are linked to environmental factors or defective inherited genes, according to the findings.

But the scientists warn that poor lifestyle can add to the “bad luck factor” involved in cancer.

The researchers analysed published data on the number of divisions of self-renewing stem cells that occur in an average lifetime in 31 different tissues.

These results were compared with the lifetime incidence of cancer in the same tissues.

A strong correlation was seen between a particular tissue’s stem cell division rate and its likelihood of developing cancer.

The more often cells divide, the more likely it is that letters of their genetic code will become jumbled, leading to an increased cancer risk.

Overall, the study found that random mutations due to stem cell division could explain around 65 per cent of cancer incidence.

Professor Bert Vogelstein, from Johns Hopkins University School of Medicine in the US, said: “All cancers are caused by a combination of bad luck, the environment and heredity, and we’ve created a model that may help quantify how much of these three factors contribute to cancer development.

“This study shows that you can add to your risk of getting cancers by smoking or other poor lifestyle factors. However, many forms of cancer are due largely to the bad luck of acquiring a mutation in a cancer driver gene regardless of lifestyle and heredity factors. The best way to eradicate these cancers will be through early detection, when they are still curable by surgery.”

Scientists have known for more than a century that some tissue types give rise to cancer millions of times more often than others, but why this should be so has not been clear.

The new evidence, published in the journal Science, suggests that the answer chiefly lies in the number of times a tissue's stem cells divide and replicate their DNA.

“Bad luck” mutations that occur when one chemical letter in DNA is wrongly swapped for another during cell replication largely explained 22 of the 31 cancer types studied. The remaining nine had incidence rates higher than predicted by bad luck, presumably due to the influence of environmental or inherited factors.

“We found that the types of cancer that had higher risk than predicted by the number of stem cell divisions were precisely the ones you’d expect, including lung cancer, which is linked to smoking; skin cancer, linked to sun exposure; and forms of cancers associated with hereditary syndromes,” Prof Vogelstein added.

People who live a long life despite exposure to cancer-causing agents such as tobacco are not so much blessed with “good genes” as good luck, said the professor.

He pointed out that human colon – or large intestine – tissue underwent four times more stem cell divisions than small intestine tissue. And colon cancer was much more prevalent than small intestine cancer.

In mice, the situation was reversed, with the colon undergoing fewer stem cell divisions and being less prone to cancer than the small intestine.

Co-author biomathematician Dr Cristian Tomasetti, also from Johns Hopkins University, said: “If two-thirds of cancer incidence across tissues is explained by random DNA mutations that occur when stem cells divide, then changing our lifestyle and habits will be a huge help in preventing certain cancers, but this may not be as effective for a variety of others.

“We should focus more resources on finding ways to detect such cancers at early, curable stages.”

PA