Earlier this year, a study was published with the following abstract:
Some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognized for more than a century, it has never been explained. Here, we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisions of the normal self-renewing cells maintaining that tissue’s homeostasis. These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to “bad luck,” that is, random mutations arising during DNA replication in normal, noncancerous stem cells. This is important not only for understanding the disease but also for designing strategies to limit the mortality it causes.
The study’s findings led to some controversy and debate, which may have been partially caused by a typographical error in the last sentence of the paper that said, “primary prevention measures are not likely to be effective” for 22 cancers, including melanoma.
Study co-author and medical statistician at Johns Hopkins University CristianTomasetti said the wording should have been “primary prevention measures are not ‘as’ likely to be effective.” Without the word “as,” the meaning of the sentence changed. It has since been corrected in the online version of the study.
Unfortunately, that correction wasn’t enough to prevent misinterpretations of the findings, which led to a flurry of articles with misleading titles and flawed information.
The headline on the news release from Johns Hopkins is Bad Luck of Random Mutations Plays Predominant Role in Cancer, Study Shows, which probably didn’t help matters, because the study itself is titled…
Confusion over the study’s findings and summary – and likely over the press release title – led to mainstream news headlines that included:
Let’s take a detour for a moment, because it is important to understand what the study actually found before exploring why it was misinterpreted by so many.
For the research, scientists looked at how often stem cell division, the normal process of cell renewal, takes place in 31 different tissue types, to find out whether the sheer number of divisions can lead to more mistakes (DNA mutations) occurring. They did not study tissues from two of the common forms of cancer – breast and prostate – which are known to have particular environmental triggers, such as obesity. These were not included because they could not find reliable data on the normal division rate of stem cells in these tissues, the researchers said.
Of the 31 types of cancer the researchers looked at, they determined that 22 were basically “bad luck” cancers.
But nine others appeared at rates noticeably higher than could be expected from cell division alone, which the researchers said is probably due to habits, pollution, or genetics. Lung cancer and skin cancer were two of them, and the researchers said smoking and too much sun exposure are still strongly linked to those cancers.
“Changing our lifestyle and habits will be a huge help in preventing certain cancers, but this may not be as effective for a variety of others,” Tomasetti explained.
Bert Vogelstein, study co-author and the Clayton professor of oncology at the Johns Hopkins University school of medicine, said, “Our study shows, in general, that a change in the number of stem cell divisions in a tissue type is highly correlated with a change in the incidence of cancer in that same tissue.” He added that one example is in colon tissue, which undergoes four times more stem cell divisions than small intestine tissue in humans. Colon cancer is much more prevalent than small intestinal cancer.
In an interview with BBC Radio 4 Today, Tomasetti said:
I’m not claiming any cancers, overall across the population, are the result of pure chance, but what I am claiming is there are some tissues – for example blood cancer – where there is very little evidence of any hereditary or environmental factor.
Let’s say my parents smoked all their lives and they never got lung cancer. If I strongly believed cancer was only environment, or the genes that are inherited, then since my parents didn’t get cancer I may think I must have good genes.
So I would think it would be OK to smoke. On the contrary, our study says no, my parents were just extremely lucky and played a very dangerous game.
The International Agency for Research on Cancer (IARC), the specialized cancer agency of the World Health Organization, took issue with the study, and published a press release with the following title:
Here’s an excerpt from that press release:
The International Agency for Research on Cancer (IARC), the World Health Organization’s specialized cancer agency, strongly disagrees with the conclusion of a scientific report on the causes of human cancer published in the journal Science on 2 January 2015 by Dr Cristian Tomasetti and Dr Bert Vogelstein.
The study, which has received widespread media coverage, compares the number of lifetime stem cell divisions across a wide range of tissues with lifetime cancer risk and suggests that random mutations (or “bad luck”) are “the major contributors to cancer overall, often more important than either hereditary or external environmental factors.”
For many cancers, the authors argue for a greater focus on the early detection of the disease rather than on prevention of its occurrence. If misinterpreted, this position could have serious negative consequences from both cancer research and public health perspectives.
IARC experts point to a serious contradiction with the extensive body of epidemiological evidence as well as a number of methodological limitations and biases in the analysis presented in the report.
IARC experts identified several limitations in the report 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.
Although it has long been clear that the number of cell divisions increases the risk of mutation and, therefore, of cancer, a majority of the most common cancers occurring worldwide are strongly related to environmental and lifestyle exposures. In principle, therefore, these cancers are preventable; based on current knowledge, nearly half of all cancer cases worldwide can be prevented.
IARC Director Dr. Christopher Wild was quoted in the release:
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.
Words mean things, and particularly so when translating complex scientific findings into press releases, abstracts, and articles that are meant for the general public.
So, perhaps the use of the term “bad luck” was not a wise choice by the study’s authors. That is an opinion I share with several other science writers who have published commentary on the research and media response.
In Cancer: Bad luck, bad writing, and maybe a bad paper, science journalist Tabitha M. Powledge says:
No, it did not say that two out of three cancers are caused by bad luck, as most headline writers and many journalists reported. Whatever “bad luck” means.
To my mind, inheriting faulty DNA-repair genes is bad luck, and so is being a smoker long before smoking’s dangers were known. But the resulting cancers would be classified today as, respectively, genetic and environmental rather than random or sporadic or a matter of chance or bad luck. Among the blogging discussions of this paper the terms usually mean one of two somewhat different things: “bad luck” designates either a cancer due to random (postconception) mutation or a cancer that is not preventable.
What the authors of the paper meant by “bad luck”–the term appeared in the paper’s abstract and the scare quotes are theirs–is “random mutations arising during DNA replication in normal, noncancerous stem cells.” That’s not your everyday definition of bad luck.
She goes on to add:
Vogelstein and Tomasetti set the stage for misinterpretation and complaints by calling on “bad luck.” They introduced the term in the abstract, guaranteeing that “bad luck” would be part of how the paper was explained to others. The authors defined the term precisely enough, but of course their definition–“random mutations arising during DNA replication in normal, noncancerous stem cells”–isn’t what the rest of the world means by “bad luck.”
In his piece titled Cancer ‘mainly bad luck’? An unfortunate and distracting headline, Henry Scowcroft pointed out the key criticism of the way the paper has been interpreted:
The media coverage has inadvertently jumped from talking about cancer rates in different tissues to speculating about cancer rates in the population. (Although it’s worth noting that the authors themselves still support the fact that certain cancers can be prevented by lifestyle changes.)
Scowcroft goes on to explain that
…the more often a cell divides, the more chance there is of something untoward eventually happening. So, in this sense, there’s an element of ‘bad luck’ about cancer. And it’s true that the disease can affect any of us – from the most avid gym bunny to the most determined couch potato. But we also know there are a whole host of things that affect the chances of DNA damage developing in a dividing cell.
So to ascribe a particular patient’s cancer to ‘bad luck’ is essentially impossible. It’s a combination of myriad influences, some of which we can control, others which we can’t.
Chemicals, fluctuating hormone levels, obesity, and inflammation are also thought to speed up cell division in tissues.
He quotes University of Cambridge Professor David Spiegelhalter’s response to the media stories:
Imagine there are tickets in a bucket marked cancers of different types, and a lot of blank tickets (and some marked ‘run over by bus’ etc). Smoking means you might get 20 times as many ‘lung-cancer’ tickets, but you still may be lucky and not draw one: many smokers don’t get lung cancer.
So chance plays a very strong role, even in so-called preventable cancers. This leads to the apparently paradoxical observation that most lung cancers are ’caused’ by smoking, while all lung cancers are also a matter of bad luck.
It is an established scientific fact that cancer rates are affected by lifestyle, and it is dangerous for study authors – and journalists – to suggest otherwise.
As Adam at The Stats Guy blog said:
We often see medical research badly reported in the newspapers. Often it doesn’t matter very much. But here, I think real harm could be done. The message that comes across from the media is that cancer is just a matter of luck, so changing your lifestyle won’t make much difference anyway.
We know that lifestyle is hugely important not only for cancer, but for many other diseases as well. For the media to
claimgive the impression that lifestyle isn’t important, based on a misunderstanding of what the research shows, is highly irresponsible.
Two days ago, a new study was published…with the title Substantial contribution of extrinsic risk factors to cancer development.
Here’s how the abstract begins:
Recent research has highlighted a strong correlation between tissue-specific cancer risk and the lifetime number of tissue-specific stem-cell divisions. Whether such correlation implies a high unavoidable intrinsic cancer risk has become a key public health debate with the dissemination of the ‘bad luck’ hypothesis.
What were the findings of that research?
Here’s a sample of headlines in the mainstream media so far…
Is this another case of misleading word choices and media misinterpretation of a study’s findings?
To be continued…