Mutation Types in Diverse Cancers Linked With Smoking

Highlights

Smoking claims the lives of more than six million people every year.
Mutations associated with tobacco smoke are more complex than previously thought
Signature 4 and 5 - subgroup of mutations relating to direct DNA damage by tobacco carcinogens.

Genome analysis of human tumors from smokers and non-smokers revealed significant mutational signatures that are linked with tobacco smoke.

Smoking is the risk factor for at least 17 types of cancers. Carcinogens within the cigarettes induce DNA damage which increases the smoker’s risk of acquiring cancer-causing mutations. The mechanism by which the tobacco smoke damages DNA and causes cancer causing mutations is not yet fully understood.

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‘Cancer originating in tissues directly exposed to smoke showed a signature characteristic of a known tobacco carcinogen’

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To gain more understanding into the mechanism, Ludmil B. Alexandrov et al. examined the genome sequences of 5,000 human tumors, representing 17 different types of cancer for which smoking is a risk factor.

Study Results

The subgroup of mutations relating to direct DNA damage by tobacco carcinogens include Signature 4 and Signature 5

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Signature 4 was seen in cancers derived from tissues directly exposed to smoke, such as the lungs and larynx

The occurrence of the Signature 4 genetic mutation was less in cancers from indirectly exposed tissues, such as the bladder.

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Signature 5 is of unknown origin but was found in all cancer types. The occurrence of mutation was in clockwise manner i.e. number of mutations attributable to this signature correlated with age at the time of diagnosis.

Additionally, only small differences in DNA methylation in tumors of smokers versus nonsmokers were observed.

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The findings suggest that genetic mutations rather than epigenetic changes are the main mechanism by which smoking increases cancer risk.

Smoking Statistics

Smoking is the main cause for nearly 9 out of 10 lung cancer cases
Nearly 80% of the smokers live in low and middle income countries
Nine out of 10 smokers start smoking before the age of 18 years
5 million deaths are caused by cigarette smoking
35% of Indians above 15 years of age smoke tobacco.

Source-Medindia