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Is bad luck the leading cause of cancer?

"Most cancers are caused by random mistakes in the genetic code when cells divide out of the blue, new research shows," the Daily Mail reports. But this is an oversimplification of research that…

"Most cancers are caused by random mistakes in the genetic code when cells divide out of the blue, new research shows," the Daily Mail reports.

But this is an oversimplification of research that looked at the role spontaneous random mutations play in the development of certain cancers.

It's well known that environmental and hereditary factors are the cause of many cancers.

This study looked at the influence of a third factor: random genetic mutations that occur by chance as the body's cells repeatedly divide.

Researchers analysed cancer registry data from 69 countries worldwide to estimate the proportion of cancers that could be down to chance. They estimated just over a third of cancers worldwide could be down to chance mutations.

Looking at data for 32 cancers in the Cancer Research UK (CRUK) database, this proportion leapt to two-thirds for reasons that are currently unclear.

But the research has two key limitations, both of which the researchers openly acknowledge. First, these figures are only estimates and may not be accurate.

And second, it would be a mistake to think cancers can only have one cause. A combination of all three factors – environmental, hereditary and luck – could all contribute towards a specific cancer risk.

Making sure you eat healthily, not smoking, exercising regularly, maintaining a healthy weight, moderating how much alcohol you drink, and avoiding too much sun are likely to improve your odds.

Where did the story come from?

The study was carried out by three researchers from the Johns Hopkins University School of Medicine, the Johns Hopkins Bloomberg School of Public Health, and the Johns Hopkins Kimmel Cancer Center in the US.

Funding was provided by the John Templeton Foundation, the Virginia and D. K. Ludwig Fund for Cancer Research, the Lustgarten Foundation for Pancreatic Cancer Research, and the Sol Goldman Center for Pancreatic Cancer Research.

The lead author of the study has worked, or is currently working with, a number of biotech firms with a commercial interest in cancer genetics.

The study was published in the peer-reviewed journal Science on an open access basis, so you can read it online for free.

Both the Mail Online and The Sun failed to make it clear that there's no single risk factor for cancer.

A combination of family history, environmental factors, and just pure bad luck can all contribute towards your risk of developing a certain type of cancer. 

What kind of research was this?

This analysis of cancer registry data aimed to look at the relationship between how many divisions stem cells (early-stage cells that can develop into many different types of cell) make and rates of cancer globally.

It's understood cancer is the result of the gradual build-up of gene mutations, resulting in greater numbers of abnormal cells. But the cause of these mutations is often uncertain.

It's thought some could be down to hereditary (genetic) factors and some are environmental, but the researchers explored a third factor: random chance mistakes made during normal DNA replication.

As cells divide, it's always possible that a mistake occurs when the "genetic alphabet" contained inside each cell is copied.

Previous studies suggested the chance of mistakes could come down to the repeated division of stem cells.

The researchers considered that, unlike cancers caused by hereditary or environmental factors, those caused by mistakes in stem cell division should be evenly distributed across human populations.

What did the research involve?

The researchers analysed 423 cancer registries in 69 countries available through the International Agency for Research on Cancer (IARC). This is said to give coverage of two-thirds of the global population, or 4.8 billion people.

The researchers looked at 17 different types of cancer that have stem cell data recorded in the IARC.

They analysed the relationship between the number of stem cell divisions made in a particular tissue and lifetime risk of cancer in that tissue.

They then estimated what fraction of cancers could be down to hereditary, environmental, and chance division factors.

What were the basic results?

In all the countries' data the researchers looked at, they found a significant relationship between the number of stem cell divisions in a tissue and cancer rates.

The median correlation figure from birth to age 85+ was 0.80 (95% confidence interval [CI]: 0.67 to 0.84), which indicates a very strong relationship between the two (a figure of 1.0 would be an exact correlation).

The links were generally consistent across countries, though higher in European, North American and Oceania countries (correlation 0.81 to 0.83) than Asian, African and Latin American countries (0.72 to 0.73). The bigger age range covered also gave a stronger correlation.

The researchers estimated that if environmental influences could be theoretically reduced to zero, around 35% (95% CI: 30 to 40%) of the mutations behind cancer would still be down to chance.

They then looked at 32 specific types of cancer reported in the CRUK database and estimated, overall, 29% of cancer mutations were down to environmental exposures, 5% to genetics, and 66% down to chance.

However, the proportions varied considerably by type of cancer. CRUK estimated 42% of these cancers could be preventable. 

How did the researchers interpret the results?

The researchers say their findings are consistent with previous observational studies, which have indicated the proportion of cancers that may be down to environmental factors.

They say the results "accentuate the importance of early detection and intervention to reduce deaths from the many cancers arising from unavoidable [chance] mutations." 

Conclusion

This analysis of global cancer registry data proposes simple chance as the third possible factor behind cancer-causing gene mutations, alongside well-established genetic and environmental factors.

The possibility that random gene mutations can occur when the body's cells repeatedly divide is obviously highly plausible and not really that revolutionary a theory.

However, these researchers have tried to quantify exactly what proportion of cancers could be down to chance. This brings us to the greatest limitation of this research: these are only estimates.

As the researchers themselves point out: "The actual contribution of [chance] mutations to any particular cancer type cannot be reliably estimated from such correlations."

The researchers estimated random chance could be behind just over a third of cancers worldwide. It's not immediately apparent why on the CRUK database this proportion suddenly leaps to two-thirds.

But we don't know that these figures are accurate, and they won't necessarily apply to any individual cancers.

The fact chance may be involved also doesn't take away the importance of modifiable risk factors in cancer development.

Though the CRUK database indicated two-thirds of 32 cancers could be down to chance, CRUK still estimate 42% of these cases could be prevented.

As the study's authors pointed out: "Primary prevention is the best way to reduce cancer deaths. Recognition of a third contributor to cancer – chance mutations – does not diminish the importance of primary prevention."

Making sure you eat healthily, not smoking, exercising regularly, maintaining a healthy weight, moderating how much alcohol you drink, and avoiding too much sun may not be able to completely remove your cancer risk, but does offer the best chance of leading a healthy lifestyle. 

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