Family History of Bowel Cancer?, Information for Health Professionals, Information for Patients, Lifestyle and Risk

Why cancer is not ‘just bad luck’


A global view of the genetic contribution to colorectal cancer. The highly penetrant causative mutations in familial adenomatous polyposis (FAP), Lynch syndrome, the hamartomatous polyposis syndromes and other familial conditions underlie cases of colorectal cancer (CRC) that have a strong hereditary component, with little environmental influence. However, there are also several low-penetrance mutations that contribute to CRC susceptibility in an additive way, involving interactions between genes and with environmental factors. As well as accounting for cases of hereditary CRC, these mutations are also likely to contribute to cases of CRC that are classified as 'sporadic'. In addition, although none has been identified so far, modifier genes are also likely to influence the effects of genetic and environmental factors that contribute to CRC. Therefore, the distinction between 'sporadic' and 'familial' cases and between 'genetic' and 'environmental' predisposing factors has become blurred and might be better thought of as a continuum of risks contributing to CRC development. APC, adenomatous polyposis coli; BLM, Bloom syndrome; MMR, mismatch repair; TGFβR2, transforming growth factor-β receptor 2.

A global view of the genetic contribution to colorectal cancer.
The highly penetrant causative mutations in familial adenomatous polyposis (FAP), Lynch syndrome, the hamartomatous polyposis syndromes and other familial conditions underlie cases of colorectal cancer (CRC) that have a strong hereditary component, with little environmental influence. However, there are also several low-penetrance mutations that contribute to CRC susceptibility in an additive way, involving interactions between genes and with environmental factors. As well as accounting for cases of hereditary CRC, these mutations are also likely to contribute to cases of CRC that are classified as ‘sporadic’. In addition, although none has been identified so far, modifier genes are also likely to influence the effects of genetic and environmental factors that contribute to CRC. Therefore, the distinction between ‘sporadic’ and ‘familial’ cases and between ‘genetic’ and ‘environmental’ predisposing factors has become blurred and might be better thought of as a continuum of risks contributing to CRC development. APC, adenomatous polyposis coli; BLM, Bloom syndrome; MMR, mismatch repair; TGFβR2, transforming growth factor-β receptor 2.

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.

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About kjmonahan

Service lead for Family History of Bowel Cancer Clinic

Discussion

One thought on “Why cancer is not ‘just bad luck’

  1. Reblogged this on Not enough chlorine in the gene-pool and commented:
    An excellent rebuttal to trash-journalism

    Posted by lynnsears72 | January 18, 2015, 11:59 am

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