Genetic research may help explain the link between smoking and cancer, cardiovascular disease, and a host of other diseases. In the largest study of its kind, researchers confirmed that exposure to cigarette smoke dramatically altered genes in a wide range of negative ways, including those previously linked to tumor growth, inflammatory disease, and immune system suppression.

The investigators identified 323 genes that were significantly changed by cigarette smoke. “We have long known that smoking increases a person’s risk for cancer and depresses the immune system,” study researcher Jac. C. Charlesworth, PhD, tells WebMD. “What we show here is that smoking alters the body at the DNA level.”

Cigarette smoke contains more than 4,000 individual compounds, including at least five known human carcinogens and numerous other toxins.

Previous studies attempting to examine the impact of this exposure on cellular expression have been limited by their small size, Charlesworth explains. Prior to this analysis, the largest study to examine gene expression in smokers and nonsmokers included less than 100 people.

Charlesworth and colleagues from the Southwest Foundation for Biomedical Research (SFBR) in San Antonio, were able to look for alterations in genes in the white blood cells of 1,240 Mexican Americans from 40 families, including 297 who smoked.

They were enrolled in the ongoing San Antonio Family Heart Study, which has closely tracked the family members since 1991.

The analysis was possible because the study included very detailed genetic data on each participant.

In addition to individual genes, whole networks of gene interactions were found to be impacted by cigarette smoking, Charlesworth says.
Are Alterations Reversible?

Identifying specific genetic pathways influenced by cigarette smoke exposure could help researchers who are studying the impact of smoking on individual organs, SFBR scientist Michael C. Mahaney, PhD, tells WebMD.

“Lighting up these pathways can help direct these studies,” he says.

In addition to private grants, the study was funded by the National Institutes of Health, ChemGenex Pharmaceuticals, and the AT&T Foundation.

It appears in the latest issue of the journal BMC Medical Genomics.

The researchers plan to examine the impact of other environmental exposures on genes, including alcohol and dietary fat consumption and even gender, Mahaney says.

Charlesworth, who is now working as a research fellow at Menzies Research Institute in Tasmania, Australia, says the group is also examining whether smoking and other environmentally mediated alterations in genes are reversible.

“We know the risk for many smoking-related diseases declines when people stop smoking, but we don’t know if gene expression changes gradually revert back to normal or if some are permanently altered,” she says.

(Por Salynn Boyles, WebMD, 16/07/2010)