Averting Genetic Peril

It seems that almost every day researchers discover new gene-based links
to cancer in all its ugly permutations. But while scientists are only starting to
unravel the mystery of exactly how your DNA intersects with your risk of developing
this most deeply dreaded of diseases, one positive discovery is already clear:
Your diet and lifestyle choices are more powerful than you may think.

By Lisa James

May 2008

Actress Estelle Winwood, whose career spanned 60 years, lived to be 101 smoking several packs of cigarettes every day before dying of heart failure in 1984. Her passing came almost a month after that of actor and comedian Andy Kaufman who, with a much lighter smoking his­tory, succumbed to lung cancer at age 35. Why should Winwood live malignancy-free to such a ripe old age, despite smoking’s known ties with lung cancer, yet Kaufman not make it out of his 30s? Could one simply have been blessed with a better luck of the genetic draw than the other?

There is no definitive answer, of course. But stories like these have led many people to conclude that the words “genetics,” “cancer” and “fate” are unalterably intertwined. That
feeling grows even stronger when nearly every day brings media reports of some new association between a gene (or set of genes) and one of the 300-odd diseases that fall under the cancer umbrella.

Scientists who are exploring the connection between genetics and disease reject cancer fatalism, however. For one thing, they believe genetic research will eventually allow us to attack tumors with greater precision than ever, akin to the difference between blasting a shotgun and aiming a rifle. But they also say that although cancer is linked to weaknesses within one’s DNA, the expression of those weaknesses is tied to environmental factors that play out over a lifetime. The best news is that two of these factors—the familiar duo of diet and exercise—lie within our control.

Damaged DNA
DNA, repository of the body’s master plan, is involved in two basic processes. In replication, DNA is copied when the cell divides; in transcription, it is used to create a molecule called RNA, which in turn creates whatever protein the cell is supposed to produce—like going from blueprint to spec to finished product. Various substances can interfere with either or both of these processes and if the DNA damage is especially severe the cell can start growing wildly, the first step in cancer development.

DNA is divided into units called genes, and it is at this level that much research is conducted. One of science’s biggest breakthroughs came in 2003 with the complete mapping of the human genome—the entire sequence of genes. This has sparked a gene-hunting frenzy that is helping to drive the pace of investigation into disease origin.

Cancer is no exception in this race for knowledge. For instance, in February 2008 three different research teams announced discoveries of genes associated with prostate cancer—and all on the same day. That followed the January release of a study in which 118 genes were found to be abnormally active in cancer cells. These are only a few examples among dozens.

Nature Versus Nuture
     Finding genes linked to cancer, though, is not the same as finding genes that cause it. Scientists believe all of us carry genetic mutations that could promote development of various diseases, including cancer. Whether or not that occurs depends on those defective genes being expressed—that is, the information they carry being activated. Genes can also be silenced, or turned off; in the case of genes designed to suppress tumor growth, this too can spur cancer development.
    

Genes can be turned on or off by what people encounter in their surroundings. “It’s essentially a two-part problem,” says Geoffrey Ginsburg, MD, director of the IGSP Center for Genomic Medicine at Duke University. “You might have the underlying genetics that makes you prone to cancer, but there has to be an insult—radiation, smoking, exposure to air pollutants—on top of that.” This interplay between genes and environment also explains why cancer isn’t inherited like a disease such as cystic fibrosis. “The words ‘genetic’ and ‘hereditary’ get used almost interchangeably and they shouldn’t be,” says registered dietician Karen Collins of the American Institute for Cancer Research (www.aicr.org).

The interaction of genes and surroundings helps explain why cancer-related mutations don’t always lead to disease. The best known of these may be the BRCA1 and BRCA2 mutations, which have been linked to cancers of the breast and ovary. According to a study in the Journal of the American Medical Association (1/9/08), chances of developing breast cancer vary widely among those who carry these mutations. After looking at data from more than 2,000 women, the researchers concluded that “there is no single risk associated with BRCA1 or BRCA2 carrier status, and the risks in carriers and their relatives must be influenced by other risk factors.”

Cancer genetics research is yielding early fruit in the form of improved testing. For example, a blood test can tell a woman if she carries the BRCA mutations; a positive result indicates the need for a stepped-up examination schedule. “Sequencing each individual’s DNA is not that far in the future,” says Dave Williams, PhD, director of the Linus Pauling Institute’s NIEHS Marine/Fresh­water Biomedical Sciences Center. “Eventually it’ll get cheap enough so that you can submit a sample and get your genome sequenced.”

Genetic research is also revealing new ways to tailor treatment plans to a patient’s specific needs. Researchers at the Duke Comprehensive Cancer Center have found genetic “signatures” in breast cancer that can accurately predict the recurrence risk for each individual (JAMA 4/2/08). This knowledge lets practitioners know which patients require more aggressive therapies—and which patients can be spared the side effects of unnecessary treatment.

Perhaps the most exciting work is being done on how specific nutrients can influence cancer genetics. Williams says his research with rats has shown that “exposure to polycyclic aromatic hydrocarbons [PAHs, found in air pollution] causes increases in cancer rates among the pups. But when we feed the mothers diets supplemented with indole-3-carbinol, a substance found in cruciferous vegetables [such as broccoli and cabbage], the cancer rates drop dramatically.” Scientists have also found that a deficiency of folate, a crucial B vitamin, can promote colon tumors by helping to silence genes that keep malignant cells in check (Genes & Development 12/1/07).

Keeping Your Genes from Feeling Blue
     You don’t have to wait for more research before taking preventive action. “The most important genetic test is the family history, and it’s the least expensive one as well,” Ginsburg says. Holidays and reunions present excellent opportunities to get the straight story on which relatives have or had specific disorders, including cancer.

Getting adequate exercise helps defend against cancer and practically everything else. According to Collins, one reason is that insulin resistance, the precursor to type 2 diabetes that exercise helps control, also “seems to increase the risk of several different types of cancer.”
The single biggest controllable risk factor, however, is—you guessed it—diet. (Actually, tobacco is the biggest but you did get the memo on not smoking, right?) “The latest estimate is that about 30% to 35% in the variation among cancer rates has to do with diet,” says Williams.

Some diets are more nutrient-rich than others. “Eating plant foods, such as vegetables, fruit and beans, supply a huge number of antioxidants that can possibly forestall cancer development,” Collins says. The AICR suggests cutting down on not only alcohol, which has been linked to breast cancer, but also red meat, which can produce carcinogenic compounds when cooked over high heat. Eating moderately might also help; Willams says that when scientists restrict calories in animals “you can really knock down the rate at which they get cancer.”

Another thing: While it hasn’t been proved scientifically, taking a positive view of life may very well help you maintain your health. “It’s clear that depression and isolation leads to a number of chronic diseases, including cancer,” says Ginsburg.

Don’t fall into the trap of thinking you are fated to develop cancer. Understanding your family history, exercising every day and eating a diet loaded with antioxidant-rich plant foods gives you the best possible shot at avoiding the one disease that everybody fears.

Search our articles:

ad

ad

adad

ad

ad
ad

ad

ad

ad

ad

ad

ad

ad

ad

ad

ad

ad

ad

ad

ad

ad

ad