A new study published in the journal, Nature, entitled "Substantial contribution of extrinsic risk factors to cancer development," used quantitative measures from several different perspectives to come to the conclusion that the large majority of human cancers are caused by "environmental" factors (or non-genetic), rather than intrinsic gene abnormalities or pure chance (i.e. inherited or spontaneous mutations).
The timing of this report is intriguing, since earlier this year a study in Science magazine gave an alternate view of carcinogenesis, or how cancers start. Those authors reported that cancers often begin with an unpredictable aberrancy or mutation in stem cells having little to do with outside influences. In other words "bad luck."
The Nature study was done by four faculty members of the Stony Brook Cancer Center of Stony Brook University, Long Island NY, led by Song Wu, PhD and Yusuf Hannun, MD. They wanted to determine if the unregulated, unrestrained cell division, often with distorted DNA sequences, known as cancer, are caused by random mutations. Or do external factors, such as ultraviolet radiation exposure, cigarette smoking, obesity or viruses, play a more important role in provoking the genetic mutations that initiate the runaway cell growth of cancer?
The Stony Brook researchers found that smoking, diet, excess weight, drinking and environmental conditions account for between 70 and 90 percent of gene mutations that make cancerous tumors. In modern oncology research, now scientists can observe, measure and model the malignant transformation of stem cells and progenitor cells that lead to the growth of neoplastic (cancerous) tissue. Then, using epidemiological data of cancer rates in a population, they can semi-quantitate how often such events probably occur.
The Stony Brook team reexamined the quantitative relationship between observed lifetime risk for a specific type of cancer and normal stem-cell division.
Next, they analyzed recent studies of mutational signatures ("fingerprints") in cancer. They identified 30 distinct signatures and categorized each fingerprint as resulting from intrinsic (bad luck) or extrinsic factors (environmental). Intrinsic mutations accounted for a majority of risk in a few cancers, but a majority of the cancers analyzed had a predomination of mutations with links to extrinsic factors.
Then they made use of epidemiologic data from NCI's Surveillance, Epidemiology, and End Results (SEER) program. Some cancers had relatively stable incidences over time. However, Hannun and colleagues found that rates for some types of cancer have increased steadily. This observation argues that extrinsic factors are major contributors to the risk of these cancers.
Finally, they performed computer modeling studies of known gene mutations in cancer (intrinsic factors) to derive estimates of the likelihood that a mutation arises from intrinsic processes. They found that when three or more mutations are involved in cancer onset, intrinsic factors are insufficient to explain observed risk across cancer types -- thus suggesting only a modest contribution from intrinsic factors.
These steps led to their conclusion: "Collectively, we conclude that cancer risk is heavily influenced by extrinsic factors." They deduced that only about one-quarter of cancer risk can be explained by random genetic mutations. Their main culprits in carcinogenesis included smoking (of course), viruses (specifically human papillomavirus or HPV, and hepatitis C), UV radiation (mainly from sun exposure), alcohol in excess, and obesity. Some hormonal medication, specifically estrogen-progesterone combinations, were also deemed as likely cancer-causing agents.
The "bad luck" vs. "external factors" debate is not over, yet: we may find that some cancers have stronger environmental factors while others will have stronger intrinsic factors. In the meantime, as we here at the American Council have advocated for years, there are several simple, science-based steps that every one can do to reduce the impact that some environmental factors may have on their cancer risk.
The first and most important is easy: don't smoke. We can't say that enough. But also try and avoid too much sun, too much weight gain and too much alcohol. Also get your HPV vaccine. These are the real environmental factors that may cause cancer.