Study shows that environment and behavior contribute to the majority of cancers

The study uses both data analysis and computational modelling to show that external factors play a big role in the occurrence of cancer.

Back in January, a Johns Hopkins University study was released claiming that two-thirds of adult cancers are down to random mutations, or more simply put – bad luck. Now, a team of researchers from Stony Brook University is refuting that claim, providing an alternative analysis that counters the argument, stating instead that external factors actually play a much bigger role.

While we have a strong understanding of cancer, and countless research teams across the globe are working on more effective treatments, its development is extremely complex, and there's a great deal of debate surrounding the factors that cause particular cancers. A more solid understanding of the causes will naturally improve research, leading to better-targeted treatments.

With this goal in mind, and inspired by the Johns Hopkins paper, the Stony Brook University research team set out to provide concrete evidence for behavior and environment playing a role in cancer.

"Many scientists argued against the 'bad luck' or 'random mutation' theory of cancer but provided no alternative analysis to quantify the contribution of external risk factors," said study lead author Song Wu. "Our paper provides an alternative analysis by applying four distinct analytic approaches."

First, the team examined the risk posed by tissue cell turnover – the process by which new cells are produced. Using the same data as the Johns Hopkins study, the researchers looked carefully at the relationship between lifetime risk of cancer and the division of normal tissue stem cells. They postulated that if intrinsic risk was the major factor in cancer occurring, then tissue with similar stem cell divisions would have a similar lifetime cancer risk. That correlation turned out to be pretty rare, indicating that just 10 percent of cancers were due to intrinsic risk factors.

Next, the team performed mathematical surveys on recent studies that looked at mutational signatures in cancer – the fingerprints left on cancer genomes by varying mutagenic processes. Analyzing the data, the researchers identified and categorized around 30 different signatures, determining the origin of each case. The results showed that certain cancers were more than 50 percent intrinsic, but that the majority were more than 50 percent likely to have been caused by external factors.

Still not content with the weight of evidence, the team then looked at data from the Surveillance, Epidemiology and End Results Program (SEER). Those results showed that occurrence and mortality rates for numerous cancers are actually increasing, which the researchers logically attributed to external factors.

The final part of the study didn't rely on existing data sets, but instead drew heavily on our knowledge of gene mutations in cancer, with the team creating a computational model to analyze likely intrinsic mutation rates.

It's generally accepted that at least three mutations need to happen before cancer can occur. If getting cancer is purely bad luck, then intrinsic factors would be need to be sufficient to cause multiple mutations. The model showed that this simply wasn't the case, indicating once more that intrinsic factors are only responsible for cancer in a small percentage of cases.

Overall, the researchers believe that the multi-method approach – using both data analysis and modelling – could have a big impact on cancer research efforts. Senior author and study lead Dr. Yusuf Hannun commented that it "provides a new framework to quantify the lifetime cancer risks from both intrinsic and extrinsic factors, which will have important consequences for strategizing cancer prevention, research and public spending."

The researchers published the findings of their work in the journal Nature.

5 Replies

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  • Yes, I agree with them.

    I do not at all support that 'luck' theory at all. If it were so, what would explain sudden increase in the cancers we are facing now, especially so in the younger generation.

    For a majority of cancers, it will boil down to the food we eat, the air we breathe and the water we drink, in addition to our routine daily stresses and other environmental factors.

    Also, there is a huge huge difference in what the west is facing and what India is facing. When it comes to cancer detection, reporting with symptoms and such things, for more than 80 percent of patients, we are still in the stone age.

    Every month, if not more, I see at least two or three patients with breast cancer, with such huge lumps, ulcerating through the skin and so foul smelling discharge. Even my nurses wonder, how could the lady wait so long. And not in village. I am talking here about Mumbai! India's present fight is generation of awareness. If we don't do it aggressively NOW, the future is going to see a huge death rate.

    For those who didn't know, breast cancer is now the MOST common cancer in India, males and females combined; implying, there are mush more BC cases in women, than even oral cancer or lung cancer in men.

  • Dr Sumeet, I cannot fully agree about the "luck" theory. If you really look at it, there has to be a "luck" factor or randomness in getting any disease. Consider the common flu virus - everybody is exposed to these pathogens, but some of us get the flu while the others don't. Some kind of random occurrence cannot be eliminated from the phenomenon. This does not mean that there are no cause-effect relationships in cancer. Some causality is bound to exist as the trends you mentioned seem to indicate clearly.

  • Can the Nature article be accessed online? When was it published?

  • Substantial contribution of extrinsic risk factors to cancer development

    Song Wu,Scott Powers,Wei Zhu& Yusuf A. Hannun

    Nature

    (2015)

    doi:10.1038/nature16166

    Received

    15 April 2015

    Accepted

    23 October 2015

    Published online

    16 December 2015

    Abstract

    Recent research has highlighted a strong correlation between tissue-specific cancer risk and the lifetime number of tissue-specific stem-cell divisions. Whether such correlation implies a high unavoidable intrinsic cancer risk has become a key public health debate with the dissemination of the ‘bad luck’ hypothesis. Here we provide evidence that intrinsic risk factors contribute only modestly (less than ~10–30% of lifetime risk) to cancer development. First, we demonstrate that the correlation between stem-cell division and cancer risk does not distinguish between the effects of intrinsic and extrinsic factors. We then show that intrinsic risk is better estimated by the lower bound risk controlling for total stem-cell divisions. Finally, we show that the rates of endogenous mutation accumulation by intrinsic processes are not sufficient to account for the observed cancer risks. Collectively, we conclude that cancer risk is heavily influenced by extrinsic factors. These results are important for strategizing cancer prevention, research and public health.

  • Thanks very much shubhac

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