Expect Questions From Patients Who ‘Do Everything Right’ but Still Develop Cancer

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A study reported in Science found that more than two-thirds of human cancers are caused by random mutations made during DNA replication.1 “The main message we would like to convey is that even for many patients who follow all of the guidelines from the advisory bodies—they don’t smoke, exercise regularly, eat healthy, maintain a healthy weight, do everything right—some still get cancers,” the study’s corresponding author Bert Vogelstein, MD, told The ASCO Post. “We would like to reassure patients that of course they should follow whatever guidelines are in effect, because they can definitely, unequivocally reduce their chances of cancers, but even so, some cancers will still occur.”

Just ‘Bad Luck’

Random mutations during DNA replication occur all the time, and generally more than one mutation—either a random mutation or a mutation due to lifestyle and environment factors or hereditary factors or a combination—is required to develop cancer. For example, if three mutations are required, Dr. Vogelstein explained, “in some people, those three mutations are all caused by the environment. They are the smokers. In other patients, even with lung cancer, none of those three mutations are caused by the environment. So, some patients don’t smoke and have lung cancer. And these people often ask, ‘I didn’t smoke, why do I have lung cancer? What did I do wrong?’” 

The answer, he said, is “if you didn’t smoke and you adhered to these guidelines, you did nothing wrong. It is just bad luck.” (The term “bad luck” was first used to describe variation in cancer risk due to “random mutations rising during DNA replication in normal, noncancerous cells” in a smaller study confined to the U.S. population and reported by Dr. Vogelstein and others in 2015.2)

We are on very firm, solid scientific ground now in saying that many cancers are the result of mutations that accumulate simply because cells make mistakes.
— Bert Vogelstein, MD

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Getting across the message that most cancers are not the result of heredity, lifestyle, or other environmental factors is “particularly important to me,” Dr. Vogelstein said. “I started out as a pediatrician. And if a parent with a child who has cancer looks at virtually any website and types, ‘what causes cancer?’ environment and heredity are what they would see. So, what is a parent to think? A parent could think, ‘Well, I must have given a bad gene, a predisposition to cancer to my child. Or, I inadvertently exposed him or her to some environmental carcinogen.’ We don’t need to add guilt to an already tragic situation,” Dr. Vogelstein said.

“We are on very firm, solid scientific ground now in saying that many cancers, particularly those in children, but also many in adults, are the result of mutations that accumulate simply because cells make mistakes. It is a side effect of evolution, so to speak. And there is nothing that patient or parent could have done about it.”

Early Detection and Intervention

Recognizing how mutations due to random mistakes made during DNA replication contribute to cancer “does not diminish the importance of primary prevention but emphasizes that not all cancers can be prevented by avoiding environmental risk factors,” the study authors concluded. Their results, they noted, “accentuate the importance of early detection and intervention to reduce deaths from the many cancers arising from unavoidable replication error mutations.” ■

Disclosure: Dr. Vogelstein reported no potential conflicts of interest.


1. Tomasetti C, Li L, Vogelstein B: Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention. Science 355:1330-1334, 2017.

2. Tomasetti C, Vogelstein B: Cancer etiology: Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 347:78-81, 2015.

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