Smoking Smothers Your Genes
Cigarettes leave you with more than a smoky scent on your clothes and fingernails. A new study has found strong evidence that tobacco use can chemically modify and affect the activity of genes known to increase the risk of developing cancer. The finding may give researchers a new tool to assess cancer risk among people who smoke.
DNA isn't destiny. Chemical compounds that affect the functioning of genes can bind to our genetic material, turning certain genes on or off. These so-called epigenetic modifications can influence a variety of traits, such as obesity and sexual preference. Scientists have even identified specific epigenetic patterns on the genes of people who smoke. None of the modified genes has a direct link to cancer, however, making it unclear whether these chemical alterations increase the risk of developing the disease.
In the new study, published in Human Molecular Genetics, researchers analyzed epigenetic signatures in blood cells from 374 individuals enrolled in the European Prospective Investigation into Cancer and Nutrition. EPIC, as it's known, is a massive study aimed at linking diet, lifestyle, and environmental factors to the incidence of cancer and other chronic diseases. Half of the group consisted of people who went on to develop colon or breast cancer 5 to 7 years after first joining the study, whereas the other half remained healthy.
The team, led by James Flanagan, a human geneticist at Imperial College London, discovered a distinct "epigenetic footprint" in study subjects who were smokers. Compared with people who had never smoked, these individuals had fewer chemical tags known as methyl groups—a common type of epigenetic change—on 20 different regions of their DNA. When the researchers extended the analysis to a separate group of patients and mice that had been exposed to tobacco smoke, they narrowed down the epigenetic modifications to several sites located in four genes that have been weakly linked to cancer before. All of these changes should increase the activity of these genes, Flanagan says. It's unclear why increasing the activity of the genes would cause cancer, he says, but individuals who don't have cancer tend not to have these modifications.
The study is the first to establish a close link between epigenetic modifications on a cancer gene and the risk of developing the disease, says Robert Philibert, a behavioral geneticist at the University of Iowa in Iowa City. "To the best of my knowledge, no previous genome-wide epigenetics study has taken such efforts from initial discovery to replication to experimental validation," adds Lutz Breitling, an epidemiologist who worked on epigenetics at the German Cancer Research Center in Heidelberg, Germany.
The work may lead to new ways to asses cancer risks from smoking. "Previous research into smoking has often asked people to fill out questionnaires, … which have their obvious drawbacks and inaccuracies," Flanagan says. The new study, he says, may make it possible for doctors to quantify a person's cancer risk simply through an epigenetic analysis of their DNA.
*Update 11:08 a.m., 27 December: Lutz Breitling's affiliation has been updated.