Johns Hopkins University scientists set off alarms earlier this year when they claimed the “bad luck” of random mutations largely influence cancer risk, a finding that spurred Long Island investigators to determine whether the conclusion held weight.
They say it doesn’t.
Scientists at Stony Brook University, led by Dr. Yusuf Hannun, chairman of the cancer center, studied a broad range of cancers and found that most are influenced by behavior and environment, so-called extrinsic factors.
“We applied four distinct approaches and found that the extrinsic contribution was 70 to 90 percent,” Hannun said Wednesday. He and his colleagues used sophisticated computational modeling to statistically determine that environmental and behavioral forces powerfully influence cancer risk.
The Stony Brook team, reporting in the journal Nature’s online edition Wednesday, became the first to statistically challenge the work of Dr. Bert Vogelstein and mathematician Cristian Tomasetti of Johns Hopkins. The Hopkins investigators argued in January that chance mutations play a key role in cancer risk.
Hannun said random mutations, according to his team’s calculations, are a contributor to cancer risk but there remains a black box of unknowns about the causes of cancer that still must be elucidated.
And while he does not question the role mutations play in cancer development, he does question the mathematical conclusions of the Hopkins researchers. He thinks the results send a wrongheaded public health message. If most cancer risk is caused by random events, he said, there is no way to discuss prevention with the public.
“They found a correlation between stem cell divisions and the lifetime incidence of certain cancers. We don’t disagree with that,” Hannun said.
Stem cells are the progenitors from which all cell types arise. Mutations occurring in these cells can lead to rapid, abnormal and uncontrolled cell growth, hallmarks of cancer. But Hannun said while mutations do occur, overexposure to ultraviolet light, cigarette smoking and exposure to certain cancer-causing pathogens, such as the papilloma virus, are often the powerful culprits driving malignancies.
Vogelstein and Tomasetti set off a firestorm of debate within the scientific community when their report appeared in the journal Science. The International Agency for Research on Cancer, a division of the World Health Organization, issued a stern response shortly after its publication.
Agency officials wrote that five decades of international epidemiological research have shown that most cancers occurring frequently in one population are relatively rare in others. For example, they said, colorectal cancer was once rare in Japan, but increased fourfold in just two decades. It is consistent with a major contribution of environmental and lifestyle exposures, and not simply a matter of chance, or “bad luck.”
But Vogelstein, director of Hopkins’ Ludwig Cancer Research Center and a pioneer in cancer genomics, said he was surprised by the Stony Brook team’s findings. He labeled the findings Wednesday as “strange” and defended his own work as potent for unveiling a missing link in cancer risk — the amount people themselves contribute.
Cell mutations, he said, are occurring all the time. He also said prevention is vital when it is possible, but not all cancers can be avoided.
“I trained as a pediatrician and that convinced me about the incredible importance and centrality of prevention,” Vogelstein said. “But if you ask any pediatric oncologist whether extrinsic factors influence pediatric cancers they will unequivocally say no.”
He said his research zeroed in on the intrinsic contribution of mutations. When cells divide repeatedly over a lifetime of 80 years it is impossible to avoid mutations, he said, and, unfortunately these random events may lie at the core of numerous and sometimes inexplicable cancers.
“Part of the tragedy is that children who develop cancer is the guilt of their parents. Often they feel that they may have exposed their children inadvertently to something. So this pervasive myth that most cancers are caused extrinsically that, if we ate right and lived perfect lives, we would have avoided cancer only exacerbates the guilt of parents and [adult] cancer patients.”