In a first such analysis, scientists say that cancers are driven by random mistakes in cell division which are completely outside human control.
Scientists from the Johns Hopkins Kimmel Cancer Centre have created a statistical model that measures the proportion of cancer incidence, across many tissue types, caused mainly by random mutations that occur when stem cells divide.
They came to their conclusions by searching the scientific literature for information on the cumulative total number of divisions of stem cells among 31 tissue types during an average individual's lifetime.By their measure, two-thirds of adult cancer incidence across tissues can be explained primarily by "bad luck" when these random mutations occur in genes that can drive cancer growth, while the remaining third are due to environmental factors and inherited genes.
"All cancers are caused by a combination of bad luck, the environment and heredity, and we've created a model that may help quantify how much of these three factors contribute to cancer development," says Bert Vogelstein, the Clayton Professor of Oncology at the Johns Hopkins University School of Medicine.
They found that 22 cancer types could be largely explained by the "bad luck" factor of random DNA mutations during cell division. The other nine cancer types had incidences higher than predicted by "bad luck" and were presumably due to a combination of bad luck plus environmental or inherited factors.
"We found that the types of cancer that had higher risk than predicted by the number of stem cell divisions were precisely the ones you'd expect, including lung cancer, which is linked to smoking; skin cancer, linked to sun exposure and forms of cancers associated with hereditary syndromes," says Vogelstein.
"This study shows that you can add to your risk of getting cancers by smoking or other poor lifestyle factors. However, many forms of cancer are due largely to the bad luck of acquiring a mutation in a cancer driver gene regardless of lifestyle and heredity factors. The best way to eradicate these cancers will be through early detection, when they are still curable by surgery," adds Vogelstein.
Cancer kills around six lakh people in India with 71% of these deaths occurring in people aged 30-69 years. A Lancet study earlier had said that cancer deaths accounted for 6% of deaths across all ages, but among the 30-69 years age group, this rose to 8%.
Tobacco-related cancers represented 42% of male and 18.3% of female cancer deaths at ages 30-69 years. A 30-year old man in north-eastern India had the highest chance (11·2%) of dying from cancer before 70 years of age.
"Cancer-free longevity in people exposed to cancer-causing agents, such as tobacco, is often attributed to their 'good genes,' but the truth is that most of them simply had good luck," said Vogelstein, who cautions that poor lifestyles can add to the bad luck factor in the development of cancer.
Most types of cancer can be put down to bad luck rather than risk factors such as smoking, a study has suggested. (Reuters photo)
The implications of their model range from altering public perception about cancer risk factors to the funding of cancer research, they say.
"If two-thirds of cancer incidence across tissues is explained by random DNA mutations that occur when stem cells divide, then 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," says bio mathematician Cristian Tomasetti, an assistant professor of oncology at the Johns Hopkins.
"We should focus more resources on finding ways to detect such cancers at early, curable stages," he adds.
Pancreatic cancer cells dividing. Random mutations in DNA are behind two thirds of adult cancers, a study says. (Photo: Getty Images)
It was well-known, Vogelstein notes that cancer arises when tissue-specific stem cells make random mistakes, or mutations, when one chemical letter in DNA is incorrectly swapped for another during the replication process in cell division. The more these mutations accumulate, the higher the risk that cells will grow unchecked, a hallmark of cancer.
To sort out the role of such random mutations in cancer risk, the Johns Hopkins scientists charted the number of stem cell divisions in 31 tissues and compared these rates with the lifetime risks of cancer in the same tissues among Americans. From this so-called data scatterplot, Vogelstein determined the correlation between the total number of stem cell divisions and cancer risk to be 0.804. Mathematically, the closer this value is to one, the more stem cell divisions and cancer risk are correlated.
"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," says Vogelstein. One example, he says, is in colon tissue, which undergoes four times more stem cell divisions than small intestine tissue in humans. Likewise, colon cancer is much more prevalent than small intestinal cancer.
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