The role of ‘bad luck’ in cancer incidence

New research suggests that about two-thirds of adult cancer affecting tissues can be explained by ‘bad luck’ in random mutations which occur during stem cell division. Only the remaining one-third is related to environmental factors and inherited genes.

‘Bad luck’ in swapping one chemical letter in the DNA during stem cell division is highly involved in cancer incidence (credit: artSILENSEcom/Fotolia)

‘Bad luck’ in swapping one chemical letter in the DNA during stem cell division is highly involved in cancer incidence (credit: artSILENSEcom/Fotolia)

In a study recently published in Science Magazine, a group of scientists from the Johns Hopkins Kimmel Cancer Center have created a statistical model that measures how significant are ‘unfavourable’ random mutations in the incidence of tissue cancer. “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” – says Bert Vogelstein, M.D., Professor of Oncology at the Johns Hopkins University School of Medicine, co-director of the Ludwig Center at Johns Hopkins and an investigator at the Howard Hughes Medical Institute. “Cancer-free longevity in people exposed to cancer-causing agents, such as tobacco, is often attributed to their ‘good genes’, but the truth is that most of them simply had good luck” – adds Vogelstein, who however also remarks that poor lifestyle choices can add to the ‘bad luck’ factor in cancer development.

So, how does the model work? Cancer arises when tissue-specific stem cells make random mistakes or mutations during the replication process in cell division, specifically when one chemical letter in the DNA is incorrectly swapped for another. What was not known – at least until this study – was the actual contribution of these random mistakes to cancer incidence, in comparison to hereditary or environmental factors. To sort out the role of such random mutations in cancer risk, the Johns Hopkins scientists charted the number of stem cell divisions in 31 tissues and compared these rates with the lifetime risks of cancer in the same tissues among Americans. From the data, the researchers determined the correlation between the total number of stem cell divisions and cancer risk to be 0.804 – which put in simpler words means stem cell divisions and cancer risk are strongly correlated (a value of 1 would mean absolute correlation). Since there is such strong correlation between cell division and cancer risk and errors randomly and naturally occur during the stem cell division process, the ‘bad luck’ factor in the incidence of cancer end up playing a major role against genetic and lifestyle choices – roughly 65% according to this research.

The researchers also calculated, statistically, which cancer types had an incidence predicted by the number of stem cell divisions and which had higher incidence. They found that 22 cancer types could be largely explained by the ‘bad luck’ factor of random DNA mutations during cell division. The other 9 cancer types had incidents higher than predicted by ‘bad luck’ and were presumably due to a combination of ‘bad luck’ plus 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” – says Vogelstein.

The final message of the study is clearly summarized by Vogelstein: “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”.

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Carlo Bradac

Carlo Bradac

Dr Carlo Bradac is a Research Fellow at the University of Technology, Sydney (UTS). He studied physics and engineering at the Polytechnic of Milan (Italy) where he achieved his Bachelor of Science (2004) and Master of Science (2006) in Engineering for Physics and Mathematics. During his employment experience, he worked as Application Engineer and Process Automation & Control Engineer. In 2012 he completed his PhD in Physics at Macquarie University, Sydney (Australia). He worked as a Postdoctoral Research Fellow at Sydney University and Macquarie University, before moving to UTS upon receiving the Chancellor Postdoctoral Research and DECRA Fellowships.

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