Lifestyle behaviors and environmental factors account for around 70-90% of cancer cases, according to new research published in the journal Nature.
The study contradicts a study published in the journal Science in January, which suggested the majority of cancer cases are down to “bad luck.”
In that study, Johns Hopkins researchers claimed 65% of cancer cases are a result of random DNA mutations, while the remaining 35% of cancer cases are explained by a combination of these mutations and environmental and hereditary factors.
The research spurred much debate, with many scientists arguing against the “bad luck” theory.
But Song Wu, PhD, lead author of this latest study and assistant professor of the Department of Applied Mathematics and Statistics at Stony Brook University in New York, notes that scientists had not conducted an alternative analysis to determine the extent to which external risk factors contribute to cancer development.
“Our paper provides an alternative analysis by applying four distinct analytic approaches,” he adds.
Wu and colleagues applied these four approaches to the same data that were used in the earlier Science paper.
Intrinsic factors ‘account for 10-30% of cancer cases’
One approach was an analysis of tissue cell turnover, which involved assessing the quantitive relationship between the lifetime risk for certain cancers – such as pancreatic, lung and colorectal cancers – and division of normal tissue stem cells.
Fast facts about cancer
- There will be around 1,658,370 new cancer cases diagnosed in the US this year
- Around 589,430 cancer deaths will occur in the US in 2015
- Breast cancer remains the most common cancer in women, while prostate cancer is the most common cancer for men.
The researchers explain that if intrinsic risk factors – that is, processes that result in random DNA mutations – played a key role in cancer development, then the total number of divisions in tissue stem cells would correlate with lifetime cancer risk.
However, they found this pattern was uncommon, with intrinsic factors only accounting for around 10-30% of cancer cases. “In summary, irrespective of whether a subpopulation or all dividing cells contribute to cancer, these results indicate that intrinsic factors do not play a major causal role,” say the authors.
Another approach involved mathematical analysis of recent studies on mutational cancer signatures – defined as “‘fingerprints’ left on cancer genomes by various mutagenic processes.”
The team identified 30 distinct signatures among different cancers, and they analyzed these signatures to determine the extent to which they were triggered by intrinsic or extrinsic factors – such as lifestyle and environment.
From this, the researchers found that most cancers – including lung, colorectal, bladder and thyroid cancers – possessed large numbers of mutations that were likely to have been caused by extrinsic factors; only a few cancers had large proportions of intrinsic mutations, according to the team.
Additionally, the researchers found strong epidemiological evidence supporting the high contribution of extrinsic factors to cancer development. For example, an analysis of immigrants who moved from countries with low cancer incidence to those with high cancer incidence revealed these individuals quickly acquired a higher cancer risk, suggesting extrinsic factors were to blame.
‘People can’t hide behind bad luck’
The team says their overall findings indicate that lifestyle and environmental factors account for around 70-90% of cancer cases, while intrinsic factors account for around 10-30% – findings that highly contradict those of the Science study.
Commenting on their results, the authors say:
“We have provided a new framework to quantify the lifetime cancer risks from both intrinsic and extrinsic factors on the basis of four independent approaches that are data-driven and model-driven, with and without using the stem-cell estimations[…] Collectively, we conclude that cancer risk is heavily influenced by extrinsic factors. These results are important for strategizing cancer prevention, research and public health.”
Talking to BBC News, senior author Dr. Yusuf Hannun, of the Health Sciences Center at Stony Brook, said their findings show that “people can’t hide behind bad luck.”
“They can’t smoke and say it’s bad luck if they have cancer,” he explained. “It is like a revolver – intrinsic risk is one bullet. And if playing Russian roulette, then maybe 1 in 6 will get cancer – that’s the intrinsic bad luck.”
“Now, what a smoker does is add two or three more bullets to that revolver,” Dr. Hannun continued. “And now, they pull the trigger. There is still an element of luck as not every smoker gets cancer, but they have stacked the odds against them. From a public health point of view, we want to remove as many bullets as possible from the chamber.”