Cancer is a genetic riddle; while many genes are associated with cancer, many people with cancer don’t necessarily have those genes. Conversely, many people who have “oncogenes” don’t come down with cancer.
So, what’s going on? James Flanagan, a geneticist at Imperial College London, led a research team to find out. His team discovered that smoking (long associated with lung and other cancers) can modify genes and increase risks of cancer. But not in any traditional way.
Flanagan’s research, which analyzed blood cells from 374 people enrolled in the huge European Prospective Investigation into Cancer and Nutrition (EPIC), found that epigenetic changes (occurring in so-called “junk DNA”) was causing changes that could trigger genetic predispositions to cancer. The research points to possible additional causes of cancer, but may offer more screening tools to detect a predisposition to cancer.
Smoking, it turns out, can chemically modify areas near genes known to cause cancers. These epigenetic modifications are very simple—in this case, removing a small molecule known as a methyl group. These small methyl groups (consisting of nothing more than a carbon and three hydrogen atoms), can turn a gene on or off. So, this process, called demethylation, can remove a regulatory apparatus that previously held a cancer-causing gene in check. And yes, the same demethylation can suppress a cancer-causing gene, if the methyl group was somehow allowing the oncogene to function. In Flanagan’s study, they found far fewer of these methyl groups in about 20 different regions of DNA, compared to non-smokers. Four regions were genes that were related somewhat to breast and colon cancer. People who did not have these smoking-induced modifications (demethylations) tended not to have cancer.
The study is perhaps the first to make a link between cancer and the newer science of epigenetics, which studies the 99% of our genome that does not produce genes and proteins. Epigenetic responses appear to be more regulatory in nature, controlling how a protein-coding gene can produce that protein, lie dormant, or do something in between.
The study also helps us understand why, for example, as much of 40% of a given population may have lung cancer, even though they never smoked. It is possible that other factors, like epigenetic ones, regulated their genes in such ways that oncogenes were allowed to express themselves. While this study linked smoking behavior to higher risks of cancer gene activity, the links to cancer were less clear. More research on the comprehensive behavior of our epigenetic networks is necessary to understand these risks more completely.
Meanwhile, this research does help create a risk profile; all a doctor would need to do is test a blood sample of DNA to look for these epigenetic changes.
Shenker, N., et al. (2012). Epigenome-wide association study in the European Prospective Investigation into Cancer and Nutrition (EPIC-Turin) identifies novel genetic loci associated with smoking Human Molecular Genetics DOI: 10.1093/hmg/dds488
Photo: Maegan Tintari, Flickr