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Heavy Smoking And Genetic Mutations

May 27, 2010

US researchers said Wednesday that heavy smokers who get lung cancer may have tens of thousands of genetic mutations.

A team of researchers at Roche’s biotechnology unit Genentech in California compared all the genetic changes in a 51-year-old man’s lung tumor with healthy tissue from the patient. The man had smoked an average of 25 cigarettes a day for 15 years before the tumor was removed. The researchers found 50,000 genetic mutations.

“Fifty thousand is a huge number. No one has ever reported such a high number,” said Zemin Zhang of Genentech.

“This is likely associated with the smoking history of the patient. It is very alarming,” Zhang said in a telephone interview with Reuters.

Smoking is the biggest single cause of lung cancer, and studies suggest mutations occur with each cigarette smoked.

Zhang said the ratio between the number of cigarettes the person smoked before his tumor was removed and the number of mutations in the tumor suggest that for every three cigarettes he smoked, one genetic mutation occurred.

Zhang said it gets more complicated, noting that there are DNA repair mechanisms in the body that help protect against the damage of smoking, but these become less effective over time.

The team was so shocked by the discovery they had to recheck to see if they made errors somewhere. They also looked for anything unusual about the smoker whose tumor they studied. They found nothing unusual, Zhang told Reuters.

The findings could make people contemplating taking up smoking to think twice. “If you imagine over a lifetime you are going to develop this many mutations in the genome, some people may think twice about it,” said Zhang.

Gene sequencing technology made it possible for researchers to take on such a study. The advances made it possible to look at entire genomes, rather than searching for a handful of genes that appear to be especially important in certain cancers.

This new way of studying cancer shows a much more complex picture of the disease. For example, the researchers discovered areas of the genome needed to make proteins — which are important for cell survival — had far lower rates of mutations, suggesting these areas are better protected.

The findings, however, are only reflected in one man’s genome, Zhang noted. “Obviously, we’d love to have multiple fully sequenced genomes in multiple tumors.”

The price of sequencing an entire genome is decreasing rapidly. The latest machines coming onto the market from companies like Illumina and Life Technologies can map out a patient’s entire DNA code for around $5,000.

Many companies are developing machines that will be able to do the job for as little as $1,000.

Zhang said his team worked with a private company called Complete Genomics in Mountain View, California.

The team’s findings of the study appear in the journal Nature.

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