UK researchers have reported direct evidence that taking up smoking results in epigenetic changes associated with the development of cancer.

The link between smoking and cancer has been established for decades. Smoking is the single biggest cause of cancer in the world, and years of research have confirmed that carcinogenic substances in tobacco smoke can damage DNA.

Researchers have also suspected that smoking causes so-called epigenetic changes, such as methylation, which alter gene expression without causing changes to the actual DNA sequence.

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.

The British team set out to clarify the link between smoking and methylation in a cohort of 2,011 healthy young women aged 15-19 who were originally recruited as part of a study of pre-cancerous changes to cells of the cervix.

Researchers have identified all the women from that cohort who had normal smears and who also tested negative for human papillomavirus throughout follow-up. In this subgroup of disease-free women researchers 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.

The researchers selected this group of women to ensure there were no potential cofounding factors for the detection of p16 methylation in otherwise healthy young women.

The particular gene the researchers were studying was p16, a so-called tumor suppressor gene. When it is methylated, this gene's normal tumor-suppressing function is inactivated.
Methylation of p16 has been frequently associated with the development of cancer in many parts of the body.

Because the women were all taking part in a study of cervical neoplasia, researchers used cells from cervical smears to test for methylation of p16. Her group found that women who took up smoking during the study were more than three times as likely ( odds ratio of 3.67 ) to acquire p16 methylation.

The results provide evidence that smoking does induce DNA methylation.

Source: ESMO Meeting, 2010

XagenaMedicine2010


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