Why the ‘Cancer Due to Bad Luck’ Story Needs Good Revision

In In The News by Barbara Jacoby

By: Zosia Chustecka

From: medscape.com

There has been quite a backlash to the recent news that many cancers are due to “bad luck” of random mutations, which was proclaimed in headlines around the world, and based on a report published in the January 2 issue of Science.

The International Agency for Research on Cancer (IARC), the World Health Organization’s specialized cancer agency, put out a press release to say that it “strongly disagrees with the conclusion,” and warning that the message could harm cancer research and public health.

“We already knew that for an individual to develop a certain cancer there is an element of chance, yet this has little to say about the level of cancer risk in a population,” explained IARC director Christopher Wild, PhD. “Concluding that ‘bad luck’ is the major cause of cancer would be misleading and may detract from efforts to identify the causes of the disease and effectively prevent it.”

As previously reported by Medscape Medical News, the researchers, from Johns Hopkins University in Baltimore, reported that in about two-thirds (22 of the 31) of cancer tissue types they had investigated, the cancer could be largely explained by the bad luck of random mutations that arise during DNA replication in normal noncancerous stem cells.

However, many of the news stories reported a distorting simplification of the findings, and stated that two-thirds of all cancers are due to bad luck.

There has been fierce criticism of the way that the media reported the story, but an expert argues that journalists were misled.

The Science report was accomapnied by an editorial entitled “The Bad Luck of Cancer,” and the subheading added: “Analysis suggests most cases can’t be prevented.”

But the data do not support either of these ideas, noted George Davey-Smith, MD, a clinical epidemiologist at Bristol University, United Kingdom, in a BBC News report. He also noted that “in the press release [from the Johns Hopkins School of Medicine], the authors say they’ve come up with a method to quantify the contribution of these stochastic or chance factors, which their method doesn’t,” he adds.

“It’s both in the journal and in the press release so it’s just not fair to attribute the mis-reporting of this to journalists,” Dr Davey-Smith commented.

In reaction to the huge media uptake of the story, the study authors issued further comments in a Johns Hopkins University statement, which also included the press release that had been “ammended for clarity.” The public relations officer for Johns Hopkins University, Vanessa Wasta, MBA, noted that the press release was updated to change reference from “incidence” to “risk” as a clarification in the first paragraph, but pointed out to Medscape Medical News that the original news release contained no reference to “cases” or “all” cancers, but referred to “risk” many times.

Science ran a follow-up piece, entitled “A Science Reporter’s Reflections on a Controversial Story,” in which the author returned to the researchers for clarification. “We did not claim that two-thirds of cancer cases are due to bad luck,” said lead author Christian Tomasetti, PhD, an assistant professor of oncology at the Johns Hopkins School of Medicine and the Bloomberg School of Public Health. What the study argued, he explained, was that two-thirds of the variation in cancer rates in different tissues could be explained by random bad luck.

Dr Tomasetti also said that many scientists and statisticians had also needed clarification, and that the team is now working on a technical report with additional details.

n the end, the amount of media attention given to this study was not justified by the findings, Dr Davey-Smith said in the BBC News report. “Explaining the difference in risk between the leg and the lung is of no interest to anyone and says nothing about the contribution to cancers in the population,” he commented.

The research does contain an important message for people who have cancer and lead a healthy lifestyle, according to another commentator. P.Z. Myers, PhD, a biologist and associate professor at the University of Minnesota, Morris, told the BBC: “What’s important about the study is that it does say that if you have cancer — and I think this is something people who have cancer would like to hear — it’s not something you should blame yourself for.”

Half of All Cancers Can Be Prevented, Says IACR

The IACR took issue with the study conclusion “that random mutations (or ‘bad luck’) are the major contributors to cancer overall, often more important than either hereditary or external environmental factors.”

The authors of the report, Dr Tomasetti and Bert Vogelstein, MD, Clayton Professor of Oncology at Johns Hopkins and codirector of the Ludwig Center, argue that for many cancers, there should be a greater focus on the early detection of the disease rather than on prevention of its occurrence. But the IACR warns that “if misinterpreted, this position could have serious negative consequences from both cancer research and public health perspectives.”

The agency points out that, although it has long been clear that the number of cell divisions increases the risk for mutation and, therefore, for cancer, a majority of the most common cancers occurring worldwide are strongly related to environmental and lifestyle exposures, and therefore they are, in principle, preventable.

“Based on current knowledge, nearly half of all cancer cases worldwide can be prevented,” the agency states. “This is supported in practice by rigorous scientific evidence showing decreases in cancer incidence after preventive interventions. Notable examples include drops in rates of lung cancer and other tobacco-related cancers after reductions in smoking, and declines in hepatocellular carcinoma rates among people vaccinated against hepatitis B virus.”

In addition, the agency points out that the past 5 decades of international epidemiological research have shown that most cancers that are frequent in one population are relatively rare in another and that these patterns vary over time. For example, esophageal cancer is common among men in East Africa but rare in West Africa. Colorectal cancer, once rare in Japan, has increased 4-fold in incidence in just 2 decades.

“These observations are characteristic of many common cancers and are consistent with a major contribution of environmental and lifestyle exposures, as opposed to genetic variation or chance,” the agency comments.

Criticisms of the Study

The agency also points out several limitations of the study itself. These include the emphasis on very rare cancers (e.g., osteosarcoma, medulloblastoma) that together make only a small contribution to the total cancer burden. The report also excludes, because of the lack of data, common cancers for which incidence differs substantially between populations and over time. The latter category includes some of the most frequent cancers worldwide (for example, those of the stomach, cervix, and breast, each known to be associated with infections or lifestyle and environmental factors). Moreover, the study focuses exclusively on the United States population as a measure of lifetime risk. The comparison of different populations would have yielded different results, the agency contends.

Other researchers have also raised questions over the way in which the research was conducted, and the research has stimulated much detailed discussion, including several blog posts from scientists, and a lengthy blog post from US oncologist David Gorski, MD, on the Science-based Medicine website. He comments that the message from the study is unpopular, adding that “human beings don’t want to hear that cancer is an unfortunately unavoidable consequence of being made of cells that replicate their DNA imperfectly over the course of our entire lives. There’s an inherent hostility to any results that conclude anything other than that we can prevent most, if not all, cancers if only we understood enough about cancer and tried hard enough.”