What causes cancer? A new study published Thursday suggests that cells make random mistakes while dividing, accounting for most of the mutations in tumors, rather than family history or environmental factors.
The paper, published in the journal Science, was authored by the same team that led a controversial study in January 2015 that said random DNA mutations - or, in other words, just "bad luck" - are often to blame for cancer.
This time, they expanded their mathematical model based on DNA sequencing and epidemiological data to 69 countries worldwide.
"Two-thirds of the mutations that occur in cancers are due to the mistakes that cells make when they divide," co-author Bert Vogelstein, co-director of the Ludwig Center at the Johns Hopkins University Kimmel Cancer Center, said at a press conference.
Environment is a factor in 29 percent of the mutations in cancer, while heredity accounts for five percent, according to the study.
"Every time a perfectly normal cell divides it makes several mistakes - mutations," Vogelstein said. "Most of the time these mutations don't do any harm."
"That is the usual situation and that is 'good luck,' in our paraphrase," he added. "But occasionally they occur in a cancer-driver gene. That is 'bad luck.'"
The goal of the study was to better understand these mutations so that better ways of detecting cancer early can be developed.
The study also shines a spotlight on cancers that will occur no matter how perfect the environment, and may alleviate the guilt some patients face when they are diagnosed.
"These copying mistakes are a potent source of cancer mutations that historically have been scientifically undervalued," said co-author Cristian Tomasetti, assistant professor of biostatistics at the Johns Hopkins Kimmel Cancer Center.
However, he still urged people to avoid known risk factors for cancer, such as smoking and too much sun exposure.
"We need to continue to encourage people to avoid environmental agents and lifestyles that increase their risk of developing cancer mutations," he said.
Vogelstein concurred, stressing that the latest research is "in perfect accord with epidemiological estimates that 42 percent of cancers can be prevented - and everyone should adhere to those prevention guidelines."
Their earlier study, based on US patients, stoked debate in the scientific community.
Critics said people might read it and believe they need not care about their diets or protect themselves from the sun if cancer were so often inevitable and unpreventable.
A study in Nature in December 2015, almost a year afterward, countered that most cases of cancer were in fact caused by environmental factors, whether from smoking or exposure to ultraviolet radiation - and not by random mutations.
But the debate is far from settled, and scientists have continued to point to flaws in the research on both sides.
"This paper certainly won't be the last word on these matters," said Kevin McConway, emeritus professor of applied statistics at the Open University.
"What I most like about it is that it provides some much-needed clarity, in making a clear distinction between the roles of environment, heredity and replication errors in producing the mutations that lead to cancer," said McConway, who was not involved in the study.
For lay people, the takeaway message is that many cases of cancer can be prevented, even though many cancerous mutations cannot.
"Despite the role of the random replication component in producing mutations, you could still reduce the cancer risk hugely, for many types of cancer, by getting rid of the environmental and/or hereditary causes," he said.
According to Lawrence Young, director of the Cancer Research Center at the University of Warwick in England, the study "contributes to the controversial debate."
However, any mathematical model that attempts to account for cancer risks must take in a variety of external factors.
"So while this study is useful in attempting to integrate epidemiological and genome sequencing data," Young said, "the message is complex and does not diminish to need to focus on improved approaches to both primary and secondary cancer prevention."