9 NOVEMBER 2006
BALTIMORE - The cause of cancer lies not in the stars (of that or any other constellation), but in the genes.
For
decades, scientists suspected that misspellings in a cell's genetic information
could spell doom in later life. You might be born with such a misspelling,
or mutation, that eventually would lead to a cancerous growth. Or some
poisonous environmental assault (say, from radiation or cigarette smoke)
might maliciously edit your genetic information to set the stage for malignancy.
Over the years, scientists realized that inherited mutations are not necessarily a death sentence, but merely a sign of susceptibility. Cancer's origin seemed to be a multi-step process, and understanding all the steps seemed to be the key to conquering cancer. But it isn't turning out to be so easy.
That's because there's more to genetics than the four-letter alphabet that spells out the code for making cellular chemicals. That code is stored in the famous molecule known as DNA, the double-helix molecule in the cell's nucleus. Strings of chemical "letters" along a DNA chain consist of three-letter words that form "sentences" known as genes. Each gene is a molecular sentence that tells a cell how to make an important molecule, typically a protein.
Relationship
of a cell, it's nucleus, a chromosome, DNA, and a gene. Image
from Genetic
Basics at NIH
Virtually all the body's cells contain the same book of sentences. Yet cells making different tissues produce different proteins and perform different tasks. Something has to tell the cell which genes to read and which to ignore -- or in other words, which genes should be active and which should remain silent. So the spelling rules are not enough -- cells need grammar rules as well. And the grammar rules seemed to be enforced by molecules that attach themselves to DNA or modify its molecular scaffolding.
Because this "grammar" goes beyond the basic spelling of DNA's genetics, it goes by the label of epigenetics. "You have this whole extra structure on this alphabet," says Andrew Feinberg, a leading epigenetics researcher at the Johns Hopkins University School of Medicine.
Molecules added to DNA not only explain why some genes are active and others aren't, but may help explain why diseases sometimes strike certain people but not others. Identical twins have the same genetic spellings, but do not always suffer from identical gene-related diseases, probably because of epigenetic differences.
"Epigenetics is at the center of gene activity and function -- and, I would argue, disease," Feinberg said at a recent meeting for science writers sponsored by the Council for the Advancement of Science Writing.
Among the diseases linked to epigenetics, he believes, is cancer. Cancer is clearly related to genetics, but you have your genes from birth and cancer usually occurs much later in life. Epigenetic factors change with aging, though, so it makes sense to see if such changes are involved in the late appearance of cancer.
In fact, epigenetic changes are found frequently among genes in tumor cells, Feinberg pointed out. And that suggests to him that the story of cancer is more than just a multistep genetic mutation process.
"I
think the way we've been looking at cancer historically is incomplete,"
he said. In the conventional view, a mutation causes a non-cancerous cell
to grow into a benign tumor, another mutation turns it into cancer and
another causes that primary cancer to spread.
That story isn't necessarily wrong, Feinberg says, just incomplete. For it may be that the original cell's propensity to divide uncontrollably and invade other tissues was programmed into that cell from the beginning. But such a cell might not become cancerous until epigenetic changes, occurring over time, prepared the cell to release its latent cancerous potential. Environmental exposures or even different diets can produce those epigenetic effects and may therefore set a stage where subsequent mutations can do their dirty work.
This view would explain why cancer runs in families (the genetic influence) and also why exposures to nasty substances like tobacco smoke are also linked to an increased cancer risk. And it would explain why cancer usually occurs late in life, after epigenetic effects have had time to accumulate.
"Maybe we could prevent cancer by treating noncancerous cells before the tumors arise," Feinberg suggested. The best war on cancer could therefore be a pre-emptive one, not relying on early diagnosis, but rather prediagnosis, stopping cancer in its tracks before it has even made any tracks.
That's the strategy that has been successful in fighting heart disease, Feinberg noted, as drugs designed to lower cholesterol are prescribed before disease strikes, not after.
"I think that's the way we should go in cancer prevention," he said. "Identify people who are at risk and give them drugs that would modify that risk."
Furthermore, Feinberg emphasizes, epigenetic effects are almost certainly not limited to cancer. Scientists today are aware of only the tip of an epigenetics iceberg, and other instances of incorrect genetic grammar may lie behind other health disorders.
"There's so much that we don't know," Feinberg said. And consequently it may turn out that understanding the grammar of cancer will spell out ways of understanding many other diseases as well.
E-mail: tsiegfried@nasw.org
