Environmental exposures and behaviors have a huge role to play in the development of a vast majority of cancers. Quantitative evidence proving the same has been found by a team of researchers from Stony Brook University, led by Yusuf Hannun, MD, the Joel Strum Kenny Professor in Cancer Research and Director of the Stony Brook University Cancer Center. The findings were published in a recent online issue of Nature. The study is significant as its findings may be important for strategizing cancer prevention, research and public health.
The study was inspired by a January 2015 research paper published in Science, which said that the majority of the variation in cancer risk among tissues is due to “bad luck”. The researchers at Stony Brook used the same data to determine what increases the risk of developing cancer. The team of researchers which had people from the Departments of Applied Mathematics and Statistics, Medicine, Pathology and Biochemistry, came to a very different conclusion that most cancers are the result of external risk factors.
Dr. Hannun, senior author of the paper remarked that development of cancer is a complex issue and that is the reason why solid analytical models are needed to investigate what intrinsic and extrinsic factors cause certain forms of cancer.
Song Wu, PhD, lead author of the paper, and Assistant Professor in the Department of Applied Mathematics and Statistics, Stony Brook University in order to argue against the ‘bad luck’ or ‘random mutation’ theory of cancer, an alternative analysis to quantify the contribution of external risk factors is a must. This study does exactly that it provides an alternative analysis by applying four distinct analytic approaches.
With the four approaches, the researchers found collectively and individually that most cancers are attributed largely to external risk factors – just 10-to-30 percent are caused due to random mutations, or intrinsic factors.
The researchers applied a data driven approach and examined extrinsic risks by tissue cell turnover. They re-examined the quantitative relationship between observed lifetime risk of cancer for lung, pancreatic, colorectal and other tissues and division of the normal tissue stem cells in those groups reported in the Science paper. The researchers argued that if intrinsic risk factors played a major role, the tissue with the similar stem cell divisions would show similar observed lifetime cancer risk. But, their study revealed that such a pattern was rare which led them to conclude that intrinsic factors played a vital role in only about 10 percent of cancers. That explains why immigrants moving from countries with lower cancer incidence to countries with higher rates of cancer incidence acquire the higher risk in their new country.
The researchers also mathematically surveyed and analyzed some 30 distinct signatures among various cancers. They signatures were analysed and categorized as having intrinsic or extrinsic origins. It was found that a few forms of cancer had a greater than 50 percent of intrinsic mutations but a majority of them like colorectal, lung, bladder and thyroid cancers were most likely caused by extrinsic factors.
Next, the team analyzed the SEER (Surveillance, Epidemiologic and End Results Program) data, which revealed that the incidences and mortality of many cancers have been increasing, suggesting that external factors contribute heavily to these cancers.
Computational modeling was also applied by the researchers to dissect the contribution of the intrinsic processes in the development of cancer. It was found that when three or more mutations are required for cancer onset, intrinsic factors are far from sufficient to account for the observed risks. This indicated that there is a small percentage of intrinsic cancer risk in many cancers.
Dr. Hannun is of the opinion that their study will have important consequences for strategizing cancer prevention, research and public health by providing a new framework to quantify the lifetime cancer risks from both intrinsic and extrinsic factors.