“Most types of cancer can be put down to bad luck rather than risk factors such as smoking,” BBC News reports. A US study estimates around two-thirds of cancer cases are caused by random

genetic mutations. The researchers who carried out the study wanted to see why cancer risk varies so much between different body tissues. For example, the average lifetime risk of lung

cancer is around 1 in 14, whereas brain cancer risk is significantly lower at around 1 in 166. The study estimates around two-thirds (65%) of cancer risk is a result of chance, based on the

number of times stem cells divide in the different tissues. However, this figure could be anywhere between 39% and 81%. This is quite a large margin of error, reducing the accuracy and

methods of reducing the risk: namely, eating a healthy balanced diet and leading an active lifestyle free of smoking and excess alcohol. WHERE DID THE STORY COME FROM? The study was carried

out by researchers from Johns Hopkins University in the US, and was funded by The Virginia and D. K. Ludwig Fund for Cancer Research, The Lustgarten Foundation for Pancreatic Cancer

Research, The Sol Goldman Center for Pancreatic Cancer Research, and US National Institutes for Health grants. It was published in the peer-reviewed journal, Science. Generally, the UK media

reported the study facts accurately, but failed to discuss any limitations, such as the breadth of the estimate of the number of cancer cases caused by chance, and so took the findings at

face value. Most news sources stressed that even if some cancers are down to chance, it is still important to take steps to reduce your cancer risk, such as by quitting smoking if you smoke.

WHAT KIND OF RESEARCH WAS THIS? This was an ecological study exploring what is behind variations in cancer risk. Ecological studies look at the effects of certain factors at the population

level. The researchers say some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognised for a long time, it has never

been fully explained. We know genetics, the number of times the tissue cells divide, and lifestyle factors such as smoking contribute to the risk of cancer in different tissues, but we are

unclear what the most important factor is. This study sought to shed more light on this issue. An ecological study is good for summarising what happens on average to groups of people.

However, it cannot tell individuals what their risk of cancer will be, as this is highly variable. WHAT DID THE RESEARCH INVOLVE? The study pooled published information on 31 tissue types,

estimating the number of times their stem cells (early-stage cells that can develop into different cell types) divided over a lifetime to renew the tissue. The researchers plotted the total

number of stem cell divisions against average lifetime risk for cancer of that tissue type, and looked for a correlation between the two. The assumption was that more cell divisions over a

lifetime would lead to a higher probability of the chance of cancer-causing mutations during this time.   The second element of the research looked at the contribution environmental factors

and inherited mutations were having on lifetime cancer risk. Cancers were subsequently grouped into those more affected by environmental and genetic factors, and those that were relatively

unaffected. WHAT WERE THE BASIC RESULTS? There was a strong correlation between the number of stem cell divisions and the lifetime risk of cancer across a range of cancers. The researchers

estimated 65% of the differences in cancer risk across tissue types were explained by the number of cell divisions in those tissues (95% confidence interval [CI] 39% to 81%). This component

was described as the “chance element”– the “bad luck”, as it cannot be controlled. In some cancers, environmental factors and inherited genetic factors did compound the risk. In relative

terms, the authors indicated the chance elements were playing the biggest role (around 65%), with environmental and genetic components adding to the risk (the remaining 35%). HOW DID THE

RESEARCHERS INTERPRET THE RESULTS? The authors concluded that, “Only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited

predispositions. “The majority is down to ‘bad luck’ – that is, random mutations arising during DNA replication in normal, non-cancerous stem cells. This is important not only for

understanding the disease, but also for designing strategies to limit the mortality it causes.” CONCLUSION This study estimates around two-thirds (65%) of cancer risk is down to chance,

based on the number of times stem cells divide in different body tissues. Other factors, including environmental factors and genetics, account for the remaining risk. However, the estimate

was quite variable, with 95% confidence intervals ranging from 39% to 81%. So only 4 out of 10 cancers may be a result of bad luck, or, alternatively, as many as 8 out of 10. The wide

estimate reduces our confidence in its accuracy. Its reliability would be increased if other research groups arrived at similar numbers by a variety of different means. The estimates put

forward in this study were based on previous research estimating the number of stem cell divisions for different tissues, and estimates of lifetime cancer risk. Any error or bias in these

two sources will reduce the reliability of calculations based on them. If the results are confirmed in future studies, they indicate chance does play a significant role in whether a person

will develop cancer. This is not completely new, but allows us to reconsider any implications for public health efforts to reduce death and disease caused by cancer. For example, one of the

effective ways to reduce the risk of developing cancer is through prevention by lifestyle modification. This research suggests efforts should be targeted at cancer types that have the

highest proportion of risk because of environmental and genetic factors. Focusing on other cancer types that are mainly related to “chance” may be a less effective use of resources. To some

extent this already happens. We know, for example, that lung cancer is increased dramatically by smoking. Lifestyle prevention measures have therefore focused on encouraging people to stop

smoking. There will always be non-smokers who get lung cancer, and smokers who don’t. But overall, there is no doubt that non-smokers as a group develop lung cancer far less frequently than

smokers. Professor Bert Vogelstein, from Johns Hopkins University School of Medicine in the US, summed this up by saying: “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.”