Environment and behavior contribute to the majority of cancers

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."