How Do Genes Affect My Risk of Cancer

Heart Disease, and Stroke?

The shape of your nose, the color of your eyes, and other traits of your family are passed on from generation to generation like newspapers rolling off a printing press.

It seems so simple but actually is so complex that scientists are still mystified by some aspects of the process. What they do know is that genes, composed of millions of encoded nitrogen molecules, carry your reproductive blueprints. And they are busy. Every day, your body's 100 trillion cells rely on genes to tell them what they are supposed to do. What could possibly go wrong?

Plenty.

"The genetic code is a set of instructions that tells cells how to function properly. A cell follows those instructions rigorously. But if one of the instructions is wrong, it then messes up how the cell functions. These mistakes can cause disease—if they prevent the cell from carrying out important tasks—or cause the cell to die," says Richard H. Myers, Ph.D., professor of neurology at Boston University School of Medicine.

Mistakes in genes are called mutations. They develop over a lifetime due to aging or exposure to harmful substances like tobacco smoke. But these spontaneous mutations are seldom passed from one generation to the next, Dr. Myers says.

A very small percentage of the time, however, the mutation is caused by a mangled gene passed on to you from one or both of your parents. People who inherit these defects, which can remain dormant for decades, are more prone to certain diseases after age 60, including some types of cancer, heart disease, and stroke, researchers say. But even if you have a family history of one of these three diseases, you are not doomed.

"Having a mutation doesn't mean that you're absolutely going to get the disease. It should just make you more cautious about monitoring your health. If you're truly concerned about your family history, there is genetic testing and counseling available that in some cases may help ease your mind," says Glenn A. Miller, Ph.D., head of the clinical studies laboratory at Genzyme Genetics, a genetic research and testing company in Framingham, Massachusetts.

Unraveling the Mystery

Researchers know less than you might think about your genes. Just sorting out what every one does is an enormous task. Each one of your cells has up to 100,000 genes. Scientists who are trying to locate and identify all of these genes believe that they won't be finished until at least 2005. For now, researchers have found and developed detection tests for only a handful.

"This effort is a marathon, and the starting gun has just gone off," Dr. Miller says. "We're still only a couple of hundred yards down the track."

But here is a look at some of this pioneering research that may help some of us forestall or combat these diseases, Dr. Miller says.

Heart disease and stroke can be all in the family. In ongoing research at the Framingham Heart Study, which has been tracking the lives of 5,209 Massachusetts adults, many now in their eighties and nineties, for almost 50 years, investigators found that strokes were three times more common among men and women whose parents had had heart disease.

In a second Framingham report, researchers concluded that people were 29 percent more likely to develop heart disease if a parent also had had cardiovascular ailments, says Dr. Myers, lead author of the study.

"I don't think we're going to find a single gene that causes these two diseases. But there are a number of genes that increase blood pressure and others that affect cholesterol. So the presence of the same genes may result in heart disease in some people and stroke in others," Dr. Myers says.

Researchers find a pair of breast cancer genes. Only 5 percent of breast cancers are hereditary. But among women who have families with a history of breast cancer and carry either the BRCA1 or BRCA2 gene (BRCA stands for "breast cancer"), the lifetime risk of breast cancer is about 80 percent, says Raymond L. White, Ph.D., director of the Huntsman Cancer Institute at the University of Utah Medical Center in Salt Lake City.

"Women who have an inherited breast cancer gene do tend to get the disease 10 to 15 years earlier than other women. But it's also true that close to half of the women who inherit the BRCA1 gene won't get their breast cancer until after age 60," Dr. White says. "Overall, the great majority of these breast cancers will develop between the ages of 50 and 70."

Other researchers have isolated genes linked to melanoma and colon and ovarian cancer, Dr. White says.

It's All Relative

But for most of us, the odds of developing an inherited form of cancer or heart disease is about as likely as winning the lottery and being struck by lightning on the same day.

To grasp how unlikely it is that you will inherit one of these diseases, think of your genetic risk in terms of a fire hazard, Dr. Miller says. If the house down the street is in flames, you probably wouldn't abandon your home. But if the fire is next door and flames are leaping onto your roof, it's time to take emergency measures.

"For the great majority of us, genetically predisposed cancers and heart disease are fires that are burning well down the block," Dr. Miller says. "Only a small number of individuals are at risk."

But if it appears that your family is prone to a particular disease, it may be worth taking some precautions, Dr. Myers says.

"If my mother or father had died of a heart attack, or my brother died of a stroke at a young age, I'd certainly tell my doctor about it. I'd also try to make some modifications in my lifestyle such as regular exercise, eating well, and not smoking," Dr. Myers says.

So before you decide to seek genetic counseling and testing, it's important to take an up-close-and-personal look at your family history. Here is how to do it.

Ask for volunteers. The more information you have, the better. Compiling all the family history that you would want can be a big job.

"If you're looking at a breast, ovarian, or other female cancer, for example, you really need to have a broad reach. So you wouldn't look only at mothers, sisters, and aunts but at first cousins, second cousins, and great-aunts," says Katherine Schneider, a genetic counselor at Dana Farber Cancer Institute in Boston.

Information about fathers, uncles, and grandparents can provide vital clues, too. Ask family members to help, she suggests. Elect a family historian to pull together all the pieces of information that others gather.

Glance forward as well as back. Most of the health information that you will need is buried deep in your family's past. But don't forget to record the health of your children and grandchildren. If they have a history of heart disease, cancer, or stroke, it may be time to seek genetic counseling, says Mary Daly, M.D., director of the Family Risk Assessment Program at Fox Chase Cancer Center in Philadelphia.

"We have some families where the daughter gets breast cancer before the mother, and then the mother goes on to get it, too," Dr. Daly says. Discovering that you carry the same mutated gene as your ill children may help you consider your options, she says.

Check everything out. If you know only that your aunt died of "female" cancer or that your grandfather had "cancer all through his body when he died," that won't help you very much, Schneider says.

"A lot of family myths about death are passed on from generation to generation," Schneider says. "It could turn out that the relative had a completely different cancer than family legend claims. It could be that he didn't have cancer or heart disease at all."

Get as many official documents as you can, including the death certificates, suggests Schneider. Your best bets are local hospitals, coroners, or the state department of vital statistics.

Dig deeper. Check out diaries, letters, old photographs, anything that will give you clues about how your relatives lived. Did they smoke? Where did they live? What were their occupations? What did they eat? Were they overweight? Did they have high blood pressure? Did they have high cholesterol levels? These questions will help you figure out if lifestyle or genetics played a bigger role in their pattern of disease, Dr. Hopkins says.

"If they all developed lung cancer, but they also smoked for 20 to 30 years, you can probably bet it wasn't inherited," Schneider says.

Is Genetic Testing Worthwhile for You?

Once you compile your family history, you might notice some patterns of heart disease, stroke, and cancer that can't be accounted for by poor diet, smoking, and other risk factors. If this is the case, you may want to consider taking the next step—genetic counseling and testing. But for most of us it is probably unnecessary, Dr. Miller says. For the most part, these diseases are caused by lifestyle factors like smoking.

Genetic counselors are available at most major medical and cancer centers, says Schneider. A counselor can help you evaluate your family history of disease and determine if genetic testing is appropriate.

If genetic testing seems apt, a laboratory technician will either draw some of your blood or use a small brush to swab a few cells from the inside of your mouth. Both methods will disclose the same genetic information, Dr. Miller says. A lab could then evaluate a sample of your cells for known genetic markers of cancer and heart disease.

It takes anywhere from three weeks to six months to get your initial results, depending on what type of testing you have. Cancer, for example, is very complex, says Dr. Myers. Researchers have to analyze thousands of genetic patterns to find the mutation that they are looking for. But once a defective gene has been detected in one family member, it usually takes only one to four weeks to check for that mutation in other relatives. Here are a couple of things to keep in mind before you seek counseling and testing.

Ask yourself why you are doing this. Before seeking genetic testing, it's important to think about all of the possible emotional and economic consequences for you and your family, says Dr. Daly.

Consider how genetic testing might affect you or your children's ability to get insurance or find employment, Dr. Daly says. Imagine how it might affect your relationship with your sister, daughter, or spouse.

Think about what you will really do with this information. Some people do nothing. Some begin getting more frequent checkups to detect these diseases early. Others opt for preventive surgery to remove cancer-prone organs, Dr. Daly says.

Imagine how you might react to positive test results. Take time to seriously contemplate these issues before making a decision to undergo testing. A certified genetic counselor will help you to understand the risks and benefits of genetic testing for you.

Get a referral. This process isn't cheap—up to $200 for counseling and more than $1,500 for testing. Ask your doctor to refer you to a genetic research project that will help pick up the tab for you, Schneider suggests.

Prescription for Prevention

Genetic defects that cause inherited forms of cancer and cardiovascular diseases are rare. Genetic testing can detect some of these mutant genes that are passed on from one generation to the next. But even if you carry a mutated gene, it doesn't mean you are doomed to develop one of these diseases. A healthy lifestyle that includes not smoking may help keep these genes dormant.

Do:

* Think carefully about the economic and social consequences of genetic testing on you and your family.

* Get a referral to a genetic testing study at a major medical center.

* Gather specific information about your ancestors and how they lived and died.

Don't:

* Panic. The vast majority of cancers, heart attacks, and strokes are not caused by inherited genetic defects. Focus on living as healthy a life as you can.