Most cases of cancer caused by 'bad luck'
Two thirds of the world's
cancer cases are a direct result of bad luck rather than faulty lifestyle or
defective DNA.
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.
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.
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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