Dec. 16 (Bloomberg) -- Each pack of cigarettes a person smokes triggers a genetic mutation that may one day lead to cancer, according to researchers who compiled the most detailed analysis of lung cancer and melanoma genes ever conducted.
Investigators compared the genetic makeup of a healthy cell and a cancerous cell taken from a 55-year-old man with lung cancer to pinpoint 23,000 mutations, almost all caused by smoking. A similar comparison of tissue taken from a 43-year-old melanoma patient found 33,000 mutations, mainly from exposure to ultraviolet light. Both studies appear in the journal Nature.
The approach is providing a ?catalogue of mutations? researchers can use to gather insight into the process of uncontrolled cell growth that leads to cancer in the human body, said Mike Stratton, deputy director of the Wellcome Trust Sanger Institute and co-head of its Cancer Genome Project. In the next decade, genetic sequencing may be widely used to identify cancer types and the most effective treatments, researchers said.
?What you?re seeing today is going to transform how we view cancer,? Stratton said at a Dec. 15 press conference. ?We were able to get quite profound insight into what processes generated the cancer and why did the cancer occur. We?re seeing every single mutation. It?s a landmark in the development of our understanding of cancer.?
It?s likely that only five or 10 of the genetic variations, dubbed driver mutations, are responsible for the cancers, said Peter Campbell, group leader at the Wellcome Trust Sanger Institute. The rest are ?passenger mutations? that were present and doing no harm when the cell turned cancerous, he said. Identifying the dangerous mutations will be the next major challenge, he said.
Lifestyle Choices
One of the most surprising findings was the extent to which lifestyle choices, specifically smoking and sun exposure, were responsible for the cancers, Campbell said. While some cancers develop because the body?s natural mechanism to repair damaged DNA is itself broken, that wasn?t the case here, he said.
The researchers found numerous examples of repaired genes, particularly in those cells that multiply most often. It appears that the damage from smoking and ultraviolet light finally overwhelmed the defensive mechanisms, said Campbell, who described smoking as a game of Russian roulette in which mutations were fired again and again until they hit a critical gene.
More than 1.3 million people die each year from lung cancer, making it the most deadly tumor type, according to the World Health Organization. The vast majority stem from genetic mutations caused by smoking, according to the researchers, who said they didn?t find a standout ?lung cancer gene.?
The majority of the 23,000 mutations, deletions and rearrangements found in the lung cancer gene were caused by the chemicals found in cigarettes, Campbell said. The mutations likely began occurring as soon as the person began smoking, and many were present for years before the cancer became apparent.
Original State
The good news is that 10 years to 15 years after a person stops smoking, their genetic profile returns to the original state, he said.
Malignant melanoma is diagnosed in more than 100,000 people in Europe and U.S. each year, causing three out of every four deaths from skin cancer. The melanoma genome carried more than 33,000 mutations, mostly with a typical signature linked to ultraviolet light exposure, the researchers said.
The researchers now plan to sequence at least 50 cancers, with tissue samples from 500 patients for each tumor type. The process, as part of the International Cancer Genome Consortium established in 2007, will take five to 10 years and identify the most common cancer causing mutations, Campbell said.
The process is getting faster and cheaper every day, Stratton said. While it took $100,000 and months to sequence the lung cancer and melanoma samples in the studies, in the next 18 months researchers should be able to complete the process in 10 days at a cost of less than $20,000, he said.
To contact the reporter on this story: Michelle Fay Cortez in London at mcortez@bloomberg.net
Investigators compared the genetic makeup of a healthy cell and a cancerous cell taken from a 55-year-old man with lung cancer to pinpoint 23,000 mutations, almost all caused by smoking. A similar comparison of tissue taken from a 43-year-old melanoma patient found 33,000 mutations, mainly from exposure to ultraviolet light. Both studies appear in the journal Nature.
The approach is providing a ?catalogue of mutations? researchers can use to gather insight into the process of uncontrolled cell growth that leads to cancer in the human body, said Mike Stratton, deputy director of the Wellcome Trust Sanger Institute and co-head of its Cancer Genome Project. In the next decade, genetic sequencing may be widely used to identify cancer types and the most effective treatments, researchers said.
?What you?re seeing today is going to transform how we view cancer,? Stratton said at a Dec. 15 press conference. ?We were able to get quite profound insight into what processes generated the cancer and why did the cancer occur. We?re seeing every single mutation. It?s a landmark in the development of our understanding of cancer.?
It?s likely that only five or 10 of the genetic variations, dubbed driver mutations, are responsible for the cancers, said Peter Campbell, group leader at the Wellcome Trust Sanger Institute. The rest are ?passenger mutations? that were present and doing no harm when the cell turned cancerous, he said. Identifying the dangerous mutations will be the next major challenge, he said.
Lifestyle Choices
One of the most surprising findings was the extent to which lifestyle choices, specifically smoking and sun exposure, were responsible for the cancers, Campbell said. While some cancers develop because the body?s natural mechanism to repair damaged DNA is itself broken, that wasn?t the case here, he said.
The researchers found numerous examples of repaired genes, particularly in those cells that multiply most often. It appears that the damage from smoking and ultraviolet light finally overwhelmed the defensive mechanisms, said Campbell, who described smoking as a game of Russian roulette in which mutations were fired again and again until they hit a critical gene.
More than 1.3 million people die each year from lung cancer, making it the most deadly tumor type, according to the World Health Organization. The vast majority stem from genetic mutations caused by smoking, according to the researchers, who said they didn?t find a standout ?lung cancer gene.?
The majority of the 23,000 mutations, deletions and rearrangements found in the lung cancer gene were caused by the chemicals found in cigarettes, Campbell said. The mutations likely began occurring as soon as the person began smoking, and many were present for years before the cancer became apparent.
Original State
The good news is that 10 years to 15 years after a person stops smoking, their genetic profile returns to the original state, he said.
Malignant melanoma is diagnosed in more than 100,000 people in Europe and U.S. each year, causing three out of every four deaths from skin cancer. The melanoma genome carried more than 33,000 mutations, mostly with a typical signature linked to ultraviolet light exposure, the researchers said.
The researchers now plan to sequence at least 50 cancers, with tissue samples from 500 patients for each tumor type. The process, as part of the International Cancer Genome Consortium established in 2007, will take five to 10 years and identify the most common cancer causing mutations, Campbell said.
The process is getting faster and cheaper every day, Stratton said. While it took $100,000 and months to sequence the lung cancer and melanoma samples in the studies, in the next 18 months researchers should be able to complete the process in 10 days at a cost of less than $20,000, he said.
To contact the reporter on this story: Michelle Fay Cortez in London at mcortez@bloomberg.net