Most of us worry, at least sometimes, about doing the right things to prevent cancer. Should I cut out bacon? Run faster? Drink less coffee? Or drink more? As we struggle to make sense of the rapidly changing and sometimes conflicting claims about cancer risk factors, we're motivated by a crucial assumption: that cancer can in fact be prevented. But how preventable is it, really?
The answer is important, because over the next several decades, cancer will become a much larger public health problem than it already is. By 2030, the number of new cancer cases in the United States is expected to increase by 30 percent, to more than two million annually. Worldwide, the outlook is even worse: The number of annual new cases will likely grow by 70 percent by 2035, thanks in large part to rapidly rising cancer rates in China, India, and other developing countries. Cancer is an expensive disease to treat, and as more patients survive longer, the health care costs will become formidable. As the top scientists at the International Agency for Research on Cancer recently put it, "Even the richest nations will struggle to meet demands of increasing patient numbers and spiralling treatment costs. No country can treat its way out of the cancer problem."
To combat cancer, the world's major national and international health organizations are strongly pushing prevention. The focus on prevention clearly makes sense—globally, the most common cancer, lung cancer, is also the most obviously preventable one. Many other major cancers are strongly linked to preventable risk factors, such as an unhealthy diet, obesity, and a lack of physical activity. The broad consensus of cancer researchers and public health officials is that cancer, in many, if not most cases, is a preventable disease. While there is no question that we need better cancer treatments, if we really want to win the war on cancer—or to use Obama's new metaphor, make the cancer moonshot—then we need to prevent the disease and not just treat it.
They argued that unavoidable, random DNA mutations, which occur routinely in our cells even in the absence of carcinogens, are "the major contributors to cancer overall, often more important than either hereditary or external environmental factors."
Given this widely accepted view, it was surprising last year when one of the world's leading cancer scientists, John Hopkins University researcher Bert Vogelstein, together with mathematician Cristian Tomasetti, claimed that cancer is much less preventable than we thought. In a widely reported study, they argued that unavoidable, random DNA mutations, which occur routinely in our cells even in the absence of carcinogens, are “the major contributors to cancer overall, often more important than either hereditary or external environmental factors." Cancer is often due to, in their words, "bad luck."
As evidence for their claim, Tomasetti and Vogelstein presented a striking correlation between the lifetime risk of certain cancers, and the number of times cells replicate in the body tissues where those cancers arise. Why is the number of cell replications important? Because each time a cell replicates, a new copy of our DNA is made, and random mutations inevitably occur in the process. These mutations can't be prevented, no matter how carefully we avoid carcinogens—the biochemical machinery that copies our DNA is very good, but not perfect. So each time a cell replicates, there is a fresh opportunity to be unlucky, by picking up a harmful mutation. Tissues with more replicating cells, like skin and colon, are therefore much more likely to acquire a cancer-causing mutation than tissues with fewer replicating cells, like brain and bone. "No other environmental or inherited factors are known to be correlated in this way across tumor types," Tomasetti and Vogelstein noted. The implication is that prevention won’t be effective for many cancers. Mutations happen, and we can't do much about it. Instead, we should focus on better screening to detect cancers early, when they can be treated more successfully.
Not surprisingly, Tomasetti and Vogelstein's claims were controversial. Critics noted that the bad luck theory of cancer was inconsistent with epidemiological studies suggesting that external risk factors are major contributors to cancer. Insisting that "a majority of cancers are preventable," scientists at the International Agency for Research on Cancer pointed to studies showing that immigrants tend to develop the cancers prevalent in their host countries, a sure sign that lifestyle and environment play a role.
But it was unclear how to reconcile the epidemiological data with Tomasetti and Vogelstein's evidence for a strong link between certain cancers and cell replications. Was the link between them spurious? Or have cancer researchers failed to recognize an important and unpreventable risk factor?
The answer, according to a recent re-analysis of Tomasetti and Vogelstein's data, is that unpreventable mutations do matter—a little. A team at Stony Brook University took a deeper look at the link between cell replication and cancer risk, and they found that, while "bad luck" mutations seem to play a role, their contribution to cancer risk over a lifetime is modest. The researchers confirmed that Tomasetti and Vogelstein's result linking cancer rates and cell replications is robust, but they also showed that the data does not rule out a major contribution by external factors. They found significant differences in cancer rates among tissues with similar numbers of cell replications, which almost certainly reflects the impact of environmental risk factors. Based on these differences in cancer rates, they estimated that, for most cancers, 70 to 90 percent of the risk could be attributed to environmental factors, and not bad luck.
This nuanced view—that both intrinsic and environmental risk factors contribute to cancer—is consistent with growing evidence that we need to think about cancer prevention and intrinsic risk factors together. Several recent studies suggest that some of us are more vulnerable than others to cancer, even if we aren't among the relatively few people who tragically inherit one of the well-known cancer-causing mutations that run in families. Many of us probably carry more subtle mutations that make us more susceptible to cancer under the right conditions. Last month, a large study of Scandinavian twins reported that there is a significant hereditary component to cancer in the general Nordic population, and not just among families with rare cancer syndromes. And recently, my Washington University colleagues found that, among a population of 4,000 cancer patients, 18 percent were born with rare mutations in genes linked to cancer—evidence that inborn mutations may contribute more broadly to cancer than we expected.
The message to take away from these genetic studies is not that cancer prevention is ineffective—it’s just the opposite. Our genes influence how we respond to our lifestyle and environment, and that means people who are more genetically susceptible to cancer stand to benefit the most from efforts to prevent it. On a national or global scale, the benefits of a "moonshot" to prevent cancer would be staggering. According to one of the best recent estimates, "more than half of the cancer occurring today is preventable by applying knowledge that we already have." By tackling tobacco use, obesity, and lack of exercise—the environmental factors linked to the most common cancers in the U.S.—we can reduce the burden of cancer more than any single drug possibly could. The molecular and genetic causes of cancer are complex, but, in most cases, the means to prevent it are not.