It was bound to arouse controversy—the assertion that “bad luck” has a predominant role in cancer. And so it has. Since it appeared in a research paper published in Science, the idea that much of the variation in lifetime cancer risk correlates with the random mutations in dividing stem cells has attracted much comment, much of it critical.

The original paper, prepared by Johns Hopkins scientists, was posted online January 2. It stimulated so much discussion that on January 7, the Johns Hopkins press office issued an addendum to the original press announcement, which had heralded the paper’s release. The addendum emphasized that no single factor causes cancer: “Some have misunderstood our research to say that two-thirds of cancer cases are due to bad luck. We want to stress that cancer is caused by a combination of many factors.”

Also, to be fair, the original paper included statements with built-in qualifications. For example: “Stochastic influences are in fact the major contributors to cancer overall, often more important than either hereditary or external environmental factors.” [Emphases added.]

Still, not all of the paper’s detractors are mollified. On January 13, the International Agency for Research on Cancer (IARC) issued a statement insisting that “most types of cancer are not due to ‘bad luck.’” The IARC also took issue with a suggestion it attributed to the Science paper: the idea that more emphasis should be placed on early detection of cancer rather than on prevention of its occurrence: “If misinterpreted, this position could have serious negative consequences from both cancer research and public health perspectives.”

More substantively, the IARC noted that its experts found “a serious contradiction with the extensive body of epidemiological evidence as well as a number of methodological limitations and biases” in the Science paper.

“The past five 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,” the IARC argued. “For example, esophageal cancer is common among men in East Africa but rare in West Africa. Colorectal cancer, once rare in Japan, increased fourfold in incidence in just two 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 (“bad luck”).

“Furthermore, IARC experts identify 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.”

Addressing the issues of detection and prevention, the Johns Hopkins addendum pointed out that “cancer is caused by a combination of factors—random DNA changes made during stem cell divisions that are not within our control, environmental exposures and inherited gene mutations. As a result, there are many opportunities for cancer prevention. The best way to prevent some cancer types is by eliminating environmental factors and by changing lifestyles.”

The addendum went on to distinguish between primary and secondary prevention. Primary prevention is about the environment and lifestyle. “Quitting smoking is one valuable example of primary prevention,” the statement read. “The best way to prevent deaths from other cancer types is to detect them and treat them early, while they are still curable. This is called secondary prevention. One of the important aspects of our research was to further highlight cancer types that could be best impacted by primary prevention versus secondary prevention.”

As for research priorities, the addendum explained that the original study’s findings did not mean that cancer research should be stalled: “Quite the opposite—our research emphasizes the likelihood that more cancers will appear in the future simply because aging increases the number of stem cell divisions. Research on primary and secondary prevention, cancer treatment, and the biology of the disease is more important than ever.”

After noting that many find it jarring to consider that a major contributing factor to cancer is beyond anyone’s control, the addendum added that, by the same token, many others find relief: “Cancer has a long history of stigmatization. Patients and family members frequently blame themselves, believing there was something they could have done to prevent their or their family member’s cancer. We have heard from many of these families and are pleased that our analysis could bring comfort and even lift the burden of guilt in those who have suffered the physical and emotional consequences of cancer.”

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