http://news.sciencemag.org/biology/2015/01/simple-math-explains-why-you-may-or-may-not-get-cancer?rss=1
Data: Tomasetti et al./Science
As the number of stem cell divisions in a tissue rises, so does the chance of cancer striking that site.
The simple math that explains why you may (or may not) get cancer
Staff Writer
Jennifer Couzin-Frankel
1 January 2015 2:00 pm
Why? That’s the first word on many lips after a cancer diagnosis. “It’s a perfectly reasonable question,” says Bert Vogelstein, a cancer geneticist at Johns Hopkins University in Baltimore, Maryland, who has spent a lifetime trying to answer it. Thanks to his friendship with a recently minted Ph.D. in applied mathematics, the two now propose a framework arguing that most cancer cases are the result of biological bad luck.
In a paper this week in Science, Vogelstein and Cristian Tomasetti, who joined the biostatistics department at Hopkins in 2013, put forth a mathematical formula to explain the genesis of cancer. Here’s how it works: Take the number of cells in an organ, identify what percentage of them are long-lived stem cells, and determine how many times the stem cells divide. With every division, there’s a risk of a cancer-causing mutation in a daughter cell. Thus, Tomasetti and Vogelstein reasoned, the tissues that host the greatest number of stem cell divisions are those most vulnerable to cancer. When Tomasetti crunched the numbers and compared them with actual cancer statistics, he concluded that this theory explained two-thirds of all cancers.
“Using the mathematics of evolution, you can really develop an engineerlike understanding of the disease,” says Martin Nowak, who studies mathematics and biology at Harvard University and has worked with Tomasetti and Vogelstein. “It’s a baseline risk of being an animal that has cells that need to divide.”
The idea emerged during one of the pair’s weekly brainstorming sessions in Vogelstein’s office. They returned to an age-old question: How much of cancer is driven by environmental factors, and how much by genetics? To solve that, Tomasetti reasoned, “I first need to understand how much is by chance and take that out of the picture.”
By “chance” Tomasetti meant the roll of the dice that each cell division represents, leaving aside the influence of deleterious genes or environmental factors such as smoking or exposure to radiation. He was most interested in stem cells because they endure—meaning that a mutation in a stem cell is more likely to cause problems than a mutation in a cell that dies more quickly.
Tomasetti searched the literature to find the numbers he needed, such as the size of the stem cell “compartment” in each tissue. Plotting the total number of stem cell divisions over a lifetime against the lifetime risk of cancer in 31 different organs revealed a correlation. As the number of divisions rose, so did risk.
Colon cancer, for example, is far more common than cancer of the duodenum, the first stretch of the small intestine. This is true even in those who carry a mutated gene that puts their entire intestine at risk. Tomasetti found that there are about 1012 stem cell divisions in the colon over a lifetime, compared with 1010 in the duodenum. Mice, by contrast, have more stem cell divisions in their small intestine—and more cancers—than in their colon.
The line between mutations and cancer isn’t necessarily direct. “It may not just be whether a mutation occurs,” says Bruce Ponder, a longtime cancer researcher at the University of Cambridge in the United Kingdom. “There may be other factors in the tissue that determine whether the mutation is retained” and whether it triggers a malignancy.
That said, the theory remains “an extremely attractive idea,” says Hans Clevers, a stem cell and cancer biologist at the Hubrecht Institute in Utrecht, the Netherlands. Still, he points out, the result “hinges entirely on how good the input data are.”
Tomasetti was aware that some of the published data may not be correct. In 10,000 runs of his model, he skewed where various points on the graph were plotted. Always, “the result was still significant,” he says, suggesting the big picture holds even if some of the data points do not. In mathematical jargon, the graph showed a correlation of 0.81. (A correlation of 1 means that by knowing the variable on the x-axis—in this case, the lifetime number of stem cell divisions—one can predict the y-axis value 100% of the time.) Squaring that 0.81 gives 0.65—an indicator of how much of the variation in cancer risk in a tissue is explained by variation in stem cell divisions (see graph above).
For Vogelstein, one major message is that cancer often cannot be prevented, and more resources should be funneled into catching it in its infancy. “These cancers are going to keep on coming,” he says.
Douglas Lowy, a deputy director of the National Cancer Institute in Bethesda, Maryland, agrees, but also stresses that a great deal of “cancer is preventable” and efforts to avert the disease must continue.
Although the randomness of cancer might be frightening, those in the field see a positive side, too. The new framework stresses that “the average cancer patient … is just unlucky,” Clevers says. “It helps cancer patients to know” that the disease is not their fault.
Posted in Biology, Health
http://www.nbcnews.com/news/us-news/biological-bad-luck-blamed-two-thirds-cancer-cases-n278146
更详细的介绍见
http://www.utsandiego.com/news/2015/jan/01/cancer-luck-vogelstein-tomasetti-hopkins/
Biological Bad Luck Blamed in Two-Thirds of Cancer Cases
Plain old bad luck plays a major role in determining who gets cancer and who does not, according to researchers who found that two-thirds of cancer incidence of various types can be blamed on random mutations and not heredity or risky habits like smoking.
The researchers said on Thursday random DNA mutations accumulating in various parts of the body during ordinary cell division are the prime culprits behind many cancer types. They looked at 31 cancer types and found that 22 of them, including leukemia and pancreatic, bone, testicular, ovarian and brain cancer, could be explained largely by these random mutations — essentially biological bad luck.
The other nine types, including colorectal cancer, skin cancer known as basal cell carcinoma and smoking-related lung cancer, were more heavily influenced by heredity and environmental factors like risky behavior or exposure to carcinogens. Overall, they attributed 65 percent of cancer incidence to random mutations in genes that can drive cancer growth.
"When someone gets cancer, immediately people want to know why," said oncologist Dr. Bert Vogelstein of the Johns Hopkins University School of Medicine in Baltimore, who conducted the study published in the journal Science with Johns Hopkins biomathematician Cristian Tomasetti.
"They like to believe there's a reason. And the real reason in many cases is not because you didn't behave well or were exposed to some bad environmental influence, it's just because that person was unlucky. It's losing the lottery." Tomasetti said harmful mutations occur for "no particular reason other than randomness" as the body's master cells, called stem cells, divide in various tissues.
— Reuters
https://www.yahoo.com/health/is-cancer-risk-mostly-affected-by-genes-[1**********]2.html
Is Cancer Risk Mostly Affected By Genes, Lifestyle, Or Just Plain Bad Luck?
Jenna Birch?
January? ?01?, ?2015
Experts say the findings highlight “the importance of secondary prevention, like early detection.” (Photo: Getty Images)
While cancer can strike anyone — young or old, unhealthy and healthy — we do have some idea of what can affect risk. Genetics often play a role, for instance, as do lifestyle habits. But according to a new study from Johns Hopkins University researchers, much of cancer risk may actually be due to mere chance.
Cancer develops when stem cells of a given tissue make random mistakes, mutating unchecked after one chemical letter of DNA is incorrectly swapped for another — the equivalent of a cell “oops.” It happens without warning, like the body’s roll of the die.
For the new study, published in the journal Science, researchers wanted to see how much of overall cancer risk was due to these unpreventable random mutations, independent of other factors like heredity and lifestyle.
“There is this question that is fundamental in cancer research: How much of cancer is due to environmental factors, and how much is due to inherited factors?” Cristian Tomasetti, PhD, a biomathematician and assistant professor of oncology at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, tells Yahoo Health. “To answer that question, however, the idea came that it would be important to determine first how much of cancer was simply due to ‘replicative chance.’”
http://news.sciencemag.org/biology/2015/01/simple-math-explains-why-you-may-or-may-not-get-cancer?rss=1
Data: Tomasetti et al./Science
As the number of stem cell divisions in a tissue rises, so does the chance of cancer striking that site.
The simple math that explains why you may (or may not) get cancer
Staff Writer
Jennifer Couzin-Frankel
1 January 2015 2:00 pm
Why? That’s the first word on many lips after a cancer diagnosis. “It’s a perfectly reasonable question,” says Bert Vogelstein, a cancer geneticist at Johns Hopkins University in Baltimore, Maryland, who has spent a lifetime trying to answer it. Thanks to his friendship with a recently minted Ph.D. in applied mathematics, the two now propose a framework arguing that most cancer cases are the result of biological bad luck.
In a paper this week in Science, Vogelstein and Cristian Tomasetti, who joined the biostatistics department at Hopkins in 2013, put forth a mathematical formula to explain the genesis of cancer. Here’s how it works: Take the number of cells in an organ, identify what percentage of them are long-lived stem cells, and determine how many times the stem cells divide. With every division, there’s a risk of a cancer-causing mutation in a daughter cell. Thus, Tomasetti and Vogelstein reasoned, the tissues that host the greatest number of stem cell divisions are those most vulnerable to cancer. When Tomasetti crunched the numbers and compared them with actual cancer statistics, he concluded that this theory explained two-thirds of all cancers.
“Using the mathematics of evolution, you can really develop an engineerlike understanding of the disease,” says Martin Nowak, who studies mathematics and biology at Harvard University and has worked with Tomasetti and Vogelstein. “It’s a baseline risk of being an animal that has cells that need to divide.”
The idea emerged during one of the pair’s weekly brainstorming sessions in Vogelstein’s office. They returned to an age-old question: How much of cancer is driven by environmental factors, and how much by genetics? To solve that, Tomasetti reasoned, “I first need to understand how much is by chance and take that out of the picture.”
By “chance” Tomasetti meant the roll of the dice that each cell division represents, leaving aside the influence of deleterious genes or environmental factors such as smoking or exposure to radiation. He was most interested in stem cells because they endure—meaning that a mutation in a stem cell is more likely to cause problems than a mutation in a cell that dies more quickly.
Tomasetti searched the literature to find the numbers he needed, such as the size of the stem cell “compartment” in each tissue. Plotting the total number of stem cell divisions over a lifetime against the lifetime risk of cancer in 31 different organs revealed a correlation. As the number of divisions rose, so did risk.
Colon cancer, for example, is far more common than cancer of the duodenum, the first stretch of the small intestine. This is true even in those who carry a mutated gene that puts their entire intestine at risk. Tomasetti found that there are about 1012 stem cell divisions in the colon over a lifetime, compared with 1010 in the duodenum. Mice, by contrast, have more stem cell divisions in their small intestine—and more cancers—than in their colon.
The line between mutations and cancer isn’t necessarily direct. “It may not just be whether a mutation occurs,” says Bruce Ponder, a longtime cancer researcher at the University of Cambridge in the United Kingdom. “There may be other factors in the tissue that determine whether the mutation is retained” and whether it triggers a malignancy.
That said, the theory remains “an extremely attractive idea,” says Hans Clevers, a stem cell and cancer biologist at the Hubrecht Institute in Utrecht, the Netherlands. Still, he points out, the result “hinges entirely on how good the input data are.”
Tomasetti was aware that some of the published data may not be correct. In 10,000 runs of his model, he skewed where various points on the graph were plotted. Always, “the result was still significant,” he says, suggesting the big picture holds even if some of the data points do not. In mathematical jargon, the graph showed a correlation of 0.81. (A correlation of 1 means that by knowing the variable on the x-axis—in this case, the lifetime number of stem cell divisions—one can predict the y-axis value 100% of the time.) Squaring that 0.81 gives 0.65—an indicator of how much of the variation in cancer risk in a tissue is explained by variation in stem cell divisions (see graph above).
For Vogelstein, one major message is that cancer often cannot be prevented, and more resources should be funneled into catching it in its infancy. “These cancers are going to keep on coming,” he says.
Douglas Lowy, a deputy director of the National Cancer Institute in Bethesda, Maryland, agrees, but also stresses that a great deal of “cancer is preventable” and efforts to avert the disease must continue.
Although the randomness of cancer might be frightening, those in the field see a positive side, too. The new framework stresses that “the average cancer patient … is just unlucky,” Clevers says. “It helps cancer patients to know” that the disease is not their fault.
Posted in Biology, Health
http://www.nbcnews.com/news/us-news/biological-bad-luck-blamed-two-thirds-cancer-cases-n278146
更详细的介绍见
http://www.utsandiego.com/news/2015/jan/01/cancer-luck-vogelstein-tomasetti-hopkins/
Biological Bad Luck Blamed in Two-Thirds of Cancer Cases
Plain old bad luck plays a major role in determining who gets cancer and who does not, according to researchers who found that two-thirds of cancer incidence of various types can be blamed on random mutations and not heredity or risky habits like smoking.
The researchers said on Thursday random DNA mutations accumulating in various parts of the body during ordinary cell division are the prime culprits behind many cancer types. They looked at 31 cancer types and found that 22 of them, including leukemia and pancreatic, bone, testicular, ovarian and brain cancer, could be explained largely by these random mutations — essentially biological bad luck.
The other nine types, including colorectal cancer, skin cancer known as basal cell carcinoma and smoking-related lung cancer, were more heavily influenced by heredity and environmental factors like risky behavior or exposure to carcinogens. Overall, they attributed 65 percent of cancer incidence to random mutations in genes that can drive cancer growth.
"When someone gets cancer, immediately people want to know why," said oncologist Dr. Bert Vogelstein of the Johns Hopkins University School of Medicine in Baltimore, who conducted the study published in the journal Science with Johns Hopkins biomathematician Cristian Tomasetti.
"They like to believe there's a reason. And the real reason in many cases is not because you didn't behave well or were exposed to some bad environmental influence, it's just because that person was unlucky. It's losing the lottery." Tomasetti said harmful mutations occur for "no particular reason other than randomness" as the body's master cells, called stem cells, divide in various tissues.
— Reuters
https://www.yahoo.com/health/is-cancer-risk-mostly-affected-by-genes-[1**********]2.html
Is Cancer Risk Mostly Affected By Genes, Lifestyle, Or Just Plain Bad Luck?
Jenna Birch?
January? ?01?, ?2015
Experts say the findings highlight “the importance of secondary prevention, like early detection.” (Photo: Getty Images)
While cancer can strike anyone — young or old, unhealthy and healthy — we do have some idea of what can affect risk. Genetics often play a role, for instance, as do lifestyle habits. But according to a new study from Johns Hopkins University researchers, much of cancer risk may actually be due to mere chance.
Cancer develops when stem cells of a given tissue make random mistakes, mutating unchecked after one chemical letter of DNA is incorrectly swapped for another — the equivalent of a cell “oops.” It happens without warning, like the body’s roll of the die.
For the new study, published in the journal Science, researchers wanted to see how much of overall cancer risk was due to these unpreventable random mutations, independent of other factors like heredity and lifestyle.
“There is this question that is fundamental in cancer research: How much of cancer is due to environmental factors, and how much is due to inherited factors?” Cristian Tomasetti, PhD, a biomathematician and assistant professor of oncology at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, tells Yahoo Health. “To answer that question, however, the idea came that it would be important to determine first how much of cancer was simply due to ‘replicative chance.’”