Smoking Shuts Down Tumor-Suppressing Genes

A new study carried out by Cancer Research UK, found a direct link between smoking and epigenetic changes, related to the development of cancer.

Smoking has been associated with cancer for a long time, and now there is a scientific evidence of that link.

Researchers suspected that smoking also causes epigenetic changes, like methylation, that affect gene expression without altering the DNA sequence.

Dr Yuk Ting Ma from the Cancer Research UK Institute of Cancer Studies, Birmingham, who presented the results, said that “until now, however, there has been no direct evidence that smoking induces DNA methylation in humans.

“Cross-sectional surveys restricted to patients with cancer have revealed that aberrant methylation of several tumor suppressor genes is associated with smoking.

“But such surveys cannot distinguish those epigenetic changes that are a consequence of the disease process from those which are directly attributable to smoking.”

This new study was carried out on 2,011 healthy women, aged 15 to 19 years old, who had been recruited for a study of pre-cancerous changes to cells of the cervix.

After using cells from cervical smears to see if the p16 gene was methylated or not, Dr Ma found that women who started smoking during the study had a three times higher risk (3.67 odds ratio) of having p16 methylation.

“Our study showed that compared with never-smokers, women who first started to smoke during follow-up had an increased risk of acquiring methylation of p16.

“Our choice of study design and our study population allowed us to reveal, for the first time, the relationship between starting to smoke and the subsequent appearance of an epigenetic change,” the researchers said.

Dr Ma said that all the women taking part at the research had normal smears and were negative for human papillomavirus throughout follow-up.

“In this subgroup of disease-free women we have then tested the cervical smears of all the women who first started to smoke following study entry for p16 methylation, and compared them to women who were never smokers,” she explained.

The p16 gene is actually a tumor-suppressing gene and when it is methylated, its main function is deactivated.

“Methylation of p16 has been frequently associated with the development of cancer in many parts of the body,” said Dr Ma.

Now, the results of this study prove that smoking induces DNA methylation, she said, so the “next step is now to show that women who acquire such smoking-induced methylation have an increased risk of developing malignancy.”

The results of the study were presented at the 35th Congress of the European Society for Medical Oncology (ESMO) in Milan, Italy.