INTRODUCTION OF GENE AND GENETIC TESTING

Genes - the chemical messages of heredity - constitute a blueprint of our possibilities and limitations. The legacy of generations of ancestors, our genes carry the key to our similarities and our uniqueness.
When genes in genetic testing are working properly, our bodies develop and function smoothly. But should a single gene - even a tiny segment of a single gene - go awry, the effect can be dramatic: deformities and disease, even death.
In the past 20 years, amazing new techniques have allowed scientists of genetic testing to learn a great deal about how genes work and how genes are linked to disease. Increasingly, researchers are able to identify mutations, changes within genes that can lead to specific disorders. In genetic testing tests for gene mutations make it possible not only to detect diseases already in progress but also, in certain situations, to foresee diseases yet to come. That is called Genetic Testing.
This new ability raises both high hopes and grave concerns. On the one hand, predictive genetic testing holds out the possibility of saving thousands of lives through prevention or early detection. On the other, the implications of test results are enormous, not only for the individual but also for relatives who share this genetic testing legacy, and for society as a whole.
This article of Genetic Testing presents key concepts and issues relevant to genetic testing and answers questions that are frequently asked about the techniques, potential risks, and possible benefits of attempts to link genetic markers with disease.

WHAT ARE GENES IN GENETIC TESTING?

In Genetic Testing Genes are working subunits of DNA. DNA, which carries the instructions that allow cells to make proteins, is made up of four chemical bases. Tightly coiled strands of DNA are packaged in units called chromosomes, housed in the cell's nucleus. Working subunits of DNA are known as genes. DNA is a vast chemical information database that carries the complete set of instructions for making all the proteins a cell will ever need. Each gene contains a particular set of instructions, usually coding for a particular protein.
DNA exists as two long, paired strands spiraled into the famous double helix. Each strand is made up of millions of chemical building blocks called bases. While there are only four different chemical bases in DNA (adenine, thymine, cytosine, and guanine), the order in which the bases occur determines the information available, much as specific letters of the alphabet combine to form words and sentences.
DNA resides in the core, or nucleus, of each of the body's trillions of cells. Every human cell (with the exception of mature red blood cells, which have no nucleus) contains the same DNA. Each cell has 46 molecules of double-stranded DNA. Each molecule is made up of 50 to 250 million bases housed in a chromosome.
The DNA in each chromosome constitutes many genes (as well as vast stretches of noncoding DNA, the function of which is unknown). A gene is any given segment along the DNA that encodes instructions that allow a cell to produce a specific product - typically, a protein such as an enzyme - that initiates one specific action. There are between 50,000 and 100,000 genes, and every gene is made up of thousands, even hundreds of thousands, of chemical bases.
Human cells contain two sets of chromosomes, one set inherited from the mother and one from the father. (Mature sperm and egg cells carry a single set of chromosomes.) Each set has 23 single chromosomes - 22 autosomes and an X or Y sex chromosome. (Females inherit an X from each parent, while males get an X from the mother and a Y from the father.)
 

 
For a cell to make protein, the information from a gene is copied, base by base, from DNA into new strands of messenger RNA (mRNA). Then mRNA travels out of the nucleus into the cytoplasm, to cell organelles called ribosomes. There, mRNA directs the assembly of amino acids that fold into completed protein molecule.

Each human cell contains 23 pairs of chromosomes, which can be distinguished by size and by unique banding patterns. This set is from a male, since it contains a Y chromosome. Females have two X chromosomes. Different genes are activated in different cells, creating the specific proteins that give a particular cell type its character.
HOW DO GENES WORK IN GENETIC TESTING?
Although each cell contains a full complement of DNA, cells use genes selectively. Some genes enable cells to make proteins needed for basic functions; dubbed housekeeping genes, they are active in many types of cells. Other genes, however, are inactive most of the time. Some genes play a role in early development of the embryo and are then shut down forever. Many genes encode proteins that are unique to a particular kind of cell and that give the cell its character - making a brain cell, say, different from a bone cell. A normal cell activates just the genes it needs at the moment and actively suppresses the rest. Genes, through the proteins they encode, determine all body processes, including how the body responds to challenges from the environment.

HOW ARE GENES LINKED TO DISEASE?
Many, if not most, diseases have their roots in our genes. Genes - through the proteins they encode - determine how efficiently we process foods, how effectively we detoxify poisons, and how vigorously we respond to infections. More than 4,000 diseases are thought to stem from mutated genes inherited from one's mother and/or father. Common disorders such as heart disease and most cancers arise from a complex interplay among multiple genes and between genes and factors in the environment.
When a gene contains a mutation, the protein encoded by that gene will be abnormal. Some protein changes are insignificant, others are disabling.

WHAT IS GENETIC TESTING?

Genetic Testing involves examining a person's DNA - taken from cells in a sample of blood or, occasionally, from other body fluids or tissues - for some anomaly that flags a disease or disorder. The DNA change can be relatively large: a missing or added piece of a chromosome - even an entire chromosome - that is visible under a microscope. Or it can be extremely small, as little as one extra, missing, or altered chemical base. Genes can be over expressed (too many copies), inactivated, or lost altogether. Sometimes, pieces of chromosomes become switched, or transposed, so that a gene ends up in a location where it is permanently and inappropriately turned on or off.
In addition to studying chromosomes or genes, genetic testing in a broader sense includes biochemical tests for the presence or absence of key proteins that signal aberrant genes.
 
WHAT ARE THE USES OF GENETIC TESTING?

Genetic Testing can be used to look for possible predisposition to disease as well as to confirm a suspected mutation in an individual or family. The most widespread type of genetic testing is newborn screening. Each year in the United States, four million newborn infants have blood samples tested for abnormal or missing gene products. Some Genetic Testing look for abnormal arrangements of the chemical bases in the gene itself, while other Genetic Testing detect inborn error of metabolism (for example, phenylketonuria) by verifying the absence of a protein that the cell needs to function normally.
Carrier testing of Genetic Testing can be used to help couples to learn if they carry - and thus risk passing to their children - a recessive allele for inherited disorders such as cystic fibrosis, sickle-cell anemia, or Tay-Sachs disease (a lethal disorder of lipid metabolism). Genetic Testing - biochemical, chromosomal, and DNA-based - also are widely available for the prenatal diagnosis of conditions such as Down syndrome.
In clinical research programs of Genetic Testing, doctors make use of Genetic Testing to identify telltale DNA changes in cancer or precancer cells. Such Genetic Testing can be helpful in several areas: early detection (familial adenomatous polyposis genes prompt close surveillance for colon cancer); diagnosis (different types of leukemia can be distinguished); prognosis (the product of a mutated p53 tumor-suppressor gene flags cancers that are likely to grow aggressively); and treatment (antibodies block a gene product that promotes the growth of breast cancer).
Much of the current excitement in Genetic Testing, however, centers on predictive gene testing: tests that identify people who are at risk of getting a disease, before any symptoms appear. Tests are already available in research programs for some two-dozen such diseases, and as more disease genes are discovered, more gene tests can be expected.
Different types of genetic Testing are used to hunt for abnormalities in whole chromosomes, in short stretches of DNA within or near genes, and in the protein products of genes.

HOW ARE DISEASE GENES IDENTIFIED IN GENETIC TESTING?

In Genetic Testing tracking down every chemical base in each of the estimated 50,000 to 100,000 genes as well as the spaces between them - mapping the human genome - is the task of an international 15-year collaboration known as the Human Genome Project. (The United States effort is shared by the National Center for Human Genome Research at the National Institutes of Health and the Office of Health and Environmental Research of the Department of Energy.) Scientists expect that having a detailed map of the entire set of human genes will revolutionize medical practice and biomedical research of Genetic Testing.
The Human Genome Project of Genetic Testing is focusing on the creation of genome maps, both genetic linkage maps and physical maps. Genome maps depict the order in which genes, genetic markers, and other landmarks are found along the chromosomes.
In narrowing the search for a specific gene in Genetic Testing, researchers often identify gene markers - characteristic segments of DNA or genes for known traits - that lie close to the target gene and are inherited along with it.
In Genetic Testing genetic linkage maps assign chromosomal locations to genetic landmarks - either genes or distinct short sequences of DNA - on the basis of how frequently markers are inherited together. Linkage maps exploit a phenomenon called recombination or crossing over. As developing sperm and egg cells divide, pairs of maternal and paternal chromosomes sometimes break and exchange pieces with one another. Genes and markers that are physically close to one another on the chromosome are said to be tightly linked; they are much less likely to be separated by recombination than are gene markers that are located far apart. In 1994, international collaborators published a comprehensive linkage map charting of Genetic Testing more than 5,000 markers and more than 400 genes.
After scientists use genetic linkage maps to assign a gene to a relatively small area on a chromosome, they next examine the region up close to learn the gene's precise location in Genetic Testing. To do this, scientists turn to physical maps.
To construct a physical map, a chromosome (or in some cases, the whole genome) is first broken into smaller pieces of DNA. Scientists then copy or clone the pieces in the laboratory, obtaining millions of identical copies of specific DNA segments. They next line up the clones to reflect the order that existed on the original chromosome. Information about the location and known genetic content of these unique and ordered DNA fragments (called contigs) is stored in a computer, while clones of the ordered pieces themselves are stored in laboratory freezers. When genetic linkage maps indicate that a gene lies in a particular region, scientists can go to the freezer and retrieve clones of interest; they then use the clones as the raw material for DNA sequencing - actually identifying the order of each and every chemical base in the gene.
Benefiting from the increasingly detailed maps and sophisticated DNA sequencing techniques and tools of Genetic Testing, scientists are mapping and isolating new disease genes at the rate of several per month. By the year 2005, scientists hope to pinpoint the location of each of the 50,000 to 100,000 genes and to identify the exact sequence of their chemical bases.
Maps of DNA can have several levels of detail; from the banding patterns of the chromosomes, to clones of overlapping segments of DNA, and ultimately to the base-by-base sequence of DNA.

WHAT TYPE OF DISEASES CAN BE PREDICTED IN GENETIC TESTING?

Predictive Genetic Testing look for disorders that "run in families" as the result of a faulty gene that is inherited.
In Genetic Testing when a mutated gene is inherited because it was carried in the reproductive cells (egg or sperm), the mutation will be present in cells throughout the body. This means that the mutation can be detected in white blood cells in a blood sample, for instance.
Predictive Genetic Testing are presently available for diseases such as Tay-Sachs disease and cystic fibrosis, and Genetic Testing are being developed for many more conditions, including a predisposition to ALS, or amyotrophic lateral sclerosis, the fatal nerve degeneration known as Lou Gehrig's disease; Huntington’s disease, a devastating disorder of middle age that causes dementia and ends in death; some forms of Alzheimer's disease; and catastrophically high cholesterol. In Genetic Testing genes have also been found for several types of cancer that can run in families.
Several of these are rare conditions that affect only a few people: a childhood eye cancer known as retinoblastoma; Wilms’ tumor, a kidney cancer that usually appears before age 5; and the Li-Fraumeni syndrome, in which children and young adults of the family develop an assortment of cancers, including sarcomas in the bones and soft tissues of the arms and legs, brain tumors, acute leukemia, and breast cancer. In 1993, from Genetic Testing scientists identified the gene that causes familial adenomatous polyposis, an inherited predisposition to form precancerous polyps. This condition is believed to be responsible for about 1 percent of colon cancers.
More recently, from Genetic Testing scientists have identified gene mutations that are linked to inherited tendencies toward common cancers, including colon cancer and breast cancer. Families who carry these altered genes may also have an increased risk of other cancers. Women with an altered copy of the BRCA1 breast cancer susceptibility gene, in particular, are susceptible to ovarian cancer as well. People who inherit cancer genes are more likely to develop cancer at a young age, because the predisposing gene damage is present throughout their lives, ready to set cancer's uncontrolled growth in motion should the normal allele be lost or inactivated.
Such inherited, or familial, forms of cancer represent perhaps about 5 to 10 percent of all cancers. The great majority of people who get breast cancer or colon cancer have not inherited such highly active altered genes. This is true even for many families that have several members with cancer; certain cancers are so common that some clusters are bound to happen purely by chance. Cases that are diagnosed at older ages, in particular, are more likely to be caused by acquired mutations.
Nevertheless, because breast and colon cancer are so widespread, even a small fraction of the total equals a very large number. It is estimated that as many as 1 in 300 women may carry inherited mutations of breast cancer susceptibility genes, and approximately the same proportion of Americans carry mutations that make them susceptible to colon cancer.
 
In Genetic Testing inherited forms of cancer represent perhaps 5 or 10 percent of all cancers. The great majority of people who get breast cancer (or colon cancer) acquire mutations during their lifetimes.

WHAT DOES A PREDICTIVE GENETIC TESTING TELL YOU?

An accurate Genetic Test will tell you if you do or do not have a disease-related gene mutation. If you do, a variety of factors can influence the gene's penetrance and the chances that you will actually develop disease. Nearly everyone with the familial adenomatous polyposis genes will - unless he or she takes effective preventive measures - someday develop colon cancer. On the other hand, women who carry the BRCA1 breast cancer susceptibility gene have an 80-percent chance of developing breast cancer by the age of 65; their risk is high but not absolute.
Of course, even family members who escape the inherited susceptibility gene are not exempt from risk. Like anyone else, they could develop mutations in that same gene during their lifetimes. Or, they could have inherited a different, unknown susceptibility gene.

In Genetic Testing scientists looking for a disease gene often begin by studying DNA samples from members of 'disease families' that have numerous relatives, over several generations, who have developed an illness.

HOW DO SCIENTISTS DEVELOP PREDICTIVE GENETIC TESTING?

In Genetic Testing scientists looking for a disease gene typically have begun by studying DNA samples from members of "disease families," in which numerous relatives, over several generations, have developed the same illness such as colon cancer. Researchers of Genetic Testing look for genetic markers - easily identifiable segments of DNA - that are consistently inherited by persons with the disease but are not found in relatives who are disease-free. Then, they painstakingly narrow down the target DNA area, pull out candidate genes, and look for specific mutations.
Before a specific gene is located in Genetic Testing, linked genetic markers can be used to test members of the family under study. However, to test wider populations, it is necessary to find the gene itself. Because the DNA highway is so vast, this can be enormously difficult. In the case of Huntington's disease, it took 10 years to advance from linkage markers to the gene.
In Genetic Testing once a disease gene has been cloned (copied to get enough to study in detail) and identified, scientists can construct DNA probes - lengths of single-stranded DNA that match parts of the known gene. (This is possible because, in double-stranded DNA, adenine in one strand always pairs with thymine in the other, and guanine pairs with cytosine.) The single-stranded probe then seeks and binds to complementary bases in the gene. When the probe has been tagged with a radioactive atom, the area of DNA it binds to - the gene - lights up. The fact of Genetic Testing is that some diseases exhibit multiple mutations within the same gene add to the complexity of gene testing.
Functional gene tests of Genetic Testing, which detect protein rather than DNA, can demonstrate not only that a mutated gene is present but also that it is actively making an abnormal protein or no protein at all.
In Genetic Testing to find a target gene mutation in a sample of DNA, scientists of Genetic Testing use a DNA probe - a length of single-stranded DNA that matches part of the gene and is linked to a radioactive atom. The single-stranded probe seeks and binds to the gene. Radioactive signals from the probe are then made visible on x-ray film, showing where the probe and gene matched.

WHAT ARE THE BENEFITS OF GENETIC TESTING?

In Genetic Testing persons in high-risk families live with troubling uncertainties about their own future as well as that of their children. A negative test - especially one that is strongly predictive - can create a tremendous sense of relief.
A negative test in Genetic Testing, especially one that is strongly predictive, also may eliminate the need for frequent checkups and tests such as annual colonoscopy (a procedure that allows a physician to view the upper reaches of the large intestine), which are routine for high-risk families concerned about cancer.
A positive test of Genetic Testing can also produce benefits. It can relieve uncertainty, and it can allow a person to make informed decisions about his or her future.
Under the best of circumstances of Genetic Testing, a positive test creates an excellent opportunity for counseling and interventions to reduce risk. The prime example is colon cancer. When tumors are caught early, chances for survival are greatest, and screening potentially could prevent thousands of cancer deaths a year. A positive Genetic Testing sounds the alert to keep up regular screening practices (annual colonoscopies to check for precancerous polyps or the earliest signs of cancer) and to maintain healthful lifestyle measures such as a high-fiber, low-fat diet and regular exercise. Another option is surgery to remove the colon before cancer has a chance to develop.

WHAT ADDITIONAL BENEFITS MAY BE EXPECTED FROM GENETIC TESTING?

In Genetic Testing tracking down the gene that causes an inherited cancer has implications for all cancers, inherited or not. A healthy allele of the same gene, if it undergoes mutations triggered by the environment during a person's lifetime, may lead to noninherited cancers. Thus, by identifying a cancer gene in Genetic Testing, scientists are able to explore mechanisms relevant to all people with cancer.
Genes and gene markers may also provide tools for improving cancer diagnosis and treatment. In Genetic Testing by spotting a mutated gene (or its protein product) in cells shed into stool, urine, or saliva, or in tissue biopsies, doctors may be able to detect cancers years earlier than with conventional diagnostic techniques. (It has even been suggested that some day probes for a mutated gene could be injected, and then traced on an x-ray.)
In Genetic Testing evaluating cancer-preventing drugs, too, should prove more efficient once the drugs can be tested in populations that are highly likely to develop the cancer. Or, if a gene is found to produce some antitumor protein, it might be possible to synthesize that protein and use it as a drug. Ultimately, it may become possible to thwart disease with gene therapy - inactivating the flawed gene or replacing it.

WHAT ARE THE LIMITATIONS OF GENETIC TESTING?

First, current Genetic Testing cannot provide a satisfactory answer for everyone who seems to be at risk for inherited breast or colon cancer. In some families, multiple cases may reflect shared environmental exposures rather than inherited susceptibility. Even when an inherited gene is to blame, it is not necessarily the test gene; the BRCA1 gene mutation, for example, is found in only about half of the families with hereditary breast cancer.
Second, despite major advances in DNA technology, identifying mutations remains a great challenge. Many of the genes of greatest interest to researchers are enormous, containing many thousands of bases. Mutations can occur anywhere, and searching through long stretches of DNA is difficult.
In addition, a single gene can have numerous mutations, not all of them equally influential. The cystic fibrosis gene, for instance, can display any one of more than 300 different mutations, which cause varying degrees of disease; some seem to cause no symptoms at all. Thus, a positive test of Genetic Testing does not guarantee that disease is imminent, while a negative test - since it evaluates only the more common mutations - cannot completely rule it out.
Furthermore, predictive tests of Genetic Testing deal in probabilities, not certainties. One person with a given gene, even one that is dominant like the hereditary breast cancer gene, may develop disease, while another person remains healthy, and no one yet knows why. A gene may respond to the commands of other genes or be switched on by an environmental factor such as sunlight.
Perhaps the most important limitation of Genetic Testing is that test information often is not matched by state-of-the-art diagnostics and therapies. Many diseases and many types of cancer still lack optimal screening procedures; it is often not possible to detect an early cancer even in an individual with a known predisposition.
In inherited breast cancer, frequent screening with mammography offers the best chance of early detection, but falls short of prevention. Moreover, mammography of Genetic Testing is least effective in the glandular breasts of young women, the very ones at greatest risk from an inherited susceptibility. For the moment, the best assurance of prevention may lie in drastic and costly surgery to remove the breasts - but even a total mastectomy can leave some breast cells behind. As for the ovarian cancer that threatens high-risk families, available screening measures often cannot discover disease in time. Here, too, women in high-risk families often opt for prophylactic surgery to remove the ovaries. To date, however, neither type of prophylactic surgery has been proven to prevent completely the occurrence of cancer.
Scientists of Genetic Testing are actively studying interventions aimed at the prevention of cancer. For example, ongoing clinical trials are evaluating the use of tamoxifen, an anticancer drug, as a breast cancer preventive. However, such approaches are still in the realm of research.

WHAT ARE THE RISKS OF GENETIC TESTING?

The physical risks of the Genetic Testing itself - usually no more than giving a blood sample - are minimal. Any potential risks have more to do with the way the results of the test might change a person's life.
Psychological impact for Genetic Testing. First, there are the emotions aroused by learning that one is - or is not - likely to develop a serious disease. Many people in disease families have already seen close relatives fall victim to the disorder. The news that they do indeed carry the disease gene can elicit depression, even despair.
Few studies to date have looked directly at the outcome of Genetic Testing for cancer. One study found that, after 3 to 6 weeks, the women identified as gene carriers experienced persistent worries, depression, confusion, and sleep disturbance. Even half of the no carriers reported that they continued to worry about their risk status.
A Genetic Testing confirming the risk of a serious disease can trigger profound psychological consequences.

Family relations. Unlike other medical tests, Genetic Testing reveal information not only about ourselves but about our relatives, and the decision to have a Genetic Testing, as well as the test results, can reverberate throughout the family. In Genetic Testing if a baby tests positive for sickle-cell trait, for example, it follows that one of his or her parents is a carrier. It is also possible for Genetic Testing to inadvertently disclose family secrets involving paternity or adoption.
Emotions elicited by test results can produce a shift in family dynamics. Someone identified as carrying the gene may feel anger, while one who has escaped may be overwhelmed by guilt for avoiding a disease that afflicts a close relative.
Family issues are especially prominent in research programs where genetic linkage tests depend on testing many members of the same family. Some family members may not want to participate in the study or know their genetic risks. People considering Genetic Testing may want to find out how their relatives would feel about knowing whether or not they have a disease gene or allowing the information to be given to others.
Someone who elects to have a Genetic Testing needs to consider whether or not to share the test results with other members of the family. Do they want to know? Who should be told - spouse, children, parents, fiancé? Should someone in a high-risk family be tested before she or he marries? What will a positive test mean to one's relationships? If one chooses not to learn the results of the family's genetic testing, can such a request be respected? How?
The question and issues raised by genetic testing can challenge family and other personal relationships.

Medical choices for Genetic Testing. Someone who tests positive for a cancer in genetic testing susceptibility gene may opt for preventive or therapeutic measures that have serious long-term implications and are potentially dangerous or of unproven value. In the first family to be tested for a BRCA1 mutation, for instance, some women chose surgery to remove their breasts - and ovaries, too, after childbearing was completed. Other families told the genetic counselor that they were not interested in even discussing surgery.
Finding ways to ensure the confidentiality of genetic testing results is a major concern.
Privacy in Genetic Testing. Our genes hold an encyclopedia of information about us and, indirectly, about our relatives. Who should be privy to that information? Will a predisposition for cancer, for instance, remain secret - or could the information slip out? The concern is that test results of genetic testing might someday be used against a person. Some people have been denied health insurance, some have lost jobs or promotions, and some have been turned down for adoptions because of their gene status.
In Genetic Testing small research studies have conscientiously established safeguards to keep DNA results under wraps. Assurances of confidentiality may be more difficult to come by when larger numbers of people have access to the results. Clinical test results of genetic testing are normally included in a person's medical records. Even if genetic testing information could be kept out of the medical record, a person's need for more frequent medical checkups, for example, could provide a tip-off to susceptibility. Might a genetic flaw constitute a "preexisting condition" that would be excluded from insurance coverage?

WHO ARE CANDIDATES FOR GENETIC TESTING?

In Genetic Testing predictive gene tests for cancer are designed to identify persons who have inherited a gene mutation that may result in cancer. First candidates are families who have participated in linkage analysis studies, where the tests have been specifically tailored to pick out the gene, or gene markers, in their DNA.
Once a gene has been isolated and a test developed, genetic testing becomes feasible in broader populations. The first candidates might be members of other very high-risk families that have had several affected members over at least two generations. Next might be persons with a family history that is less marked - perhaps one or two relatives with the disease.
Soon genetic testing for some types of inherited colon and breast cancer may be offered to the public. The targets of the genetic testing would remain the same: individuals whose body cells carry the disease-causing mutation. These would be people who have inherited the mutant gene, including those whose family history is not apparent (for example, a woman who has acquired the breast cancer susceptibility gene through her father's side of the family). It would also include people in whom the gene mutated very early in embryonic development.
It is important to remember that in genetic testing predictive gene tests will be able to identify only a small proportion of the people who will get, for example, breast or colon cancer. Most cancers are not inherited, and most people, who get cancer, whether or not they have relatives with it, do not have an inherited mutation.

WHAT OBSTACLES STAND IN THE WAY OF WIDE-SCALE TESTING OF GENETIC TESTING?

Having a blood test in genetic testing that accurately identifies a disease-causing mutation is just the first step toward wide-scale testing. Before predictive gene tests in genetic testing become generally available, specialists and society at large can come to grips with major technical, ethical, and economic concerns. These issues need to be addressed in carefully conducted research programs, and the answers are likely to be several years in coming.
Scientists of Genetic Testing are working to develop tests that are simple, cost-effective, and accurate. Genetic Testing need to be validated in broader populations, establishing that cancer susceptibility is caused by the gene mutation itself, not by other genetic or environmental factors shared by high-risk families. By comparing the cancer-causing genes of more and more people, researchers will be able to zero in on which of a gene's many mutations are significant and thus arrive at reasonably accurate predictions of disease risk.
The logistics of delivering a test to the thousands or millions of people who might want it - even limiting it initially to those with a strong family history - is daunting. Demand could quickly overwhelm the current extremely limited facilities and personnel available for DNA testing. Laboratories need to develop proficiency in these new techniques of genetic testing, and to assure accuracy and quality control.
Genetic counselors of Genetic Testing are also in short supply. People contemplating genetic testing need information and guidance in order to make informed choices and weather the psychological stresses. The demand created by widespread genetic testing would readily swamp the nation's approximately 1,200 genetic counselors, and it is likely that the task of education and counseling will fall to primary care physicians and nurses. Few primary health care providers, however, have training in this area.
Public health costs are significant. In addition to the charges for the tests themselves, there are the expenses of counseling and of follow up clinical screening and frequent monitoring. And prophylactic surgery costs many thousands of dollars.
Finally, genetic testing raises serious ethical issues, including confidentiality and discrimination. NIH is sponsoring studies of ethical issues generated by the genetics revolution, with the goal of supporting regulations and legislation to protect people from discrimination. Some states have passed legislation on health insurance discrimination and privacy. And genetic testing research is under way to develop protocols to make sure that genetic testing is never given without prior informed consent.

HOW CAN SOMEONE DECIDE WHETHER TO HAVE A GENETIC TESTING?

In 1994, a Time/CNN poll asked people whether they would take a genetic testing that could tell them what diseases they were likely to suffer later in life. Nearly as many people said they would prefer to remain ignorant (49 percent) as said they would like to know (50 percent).
The decision to undergo genetic testing is a very personal one. It should also be voluntary. A person should agree to the test only if he or she desires the information. No one considering a genetic testing should be pressured into it by relatives, health care providers, or anyone else.
Without being told whether or not treatment or preventive measures would be available, persons were asked if they would take a genetic testing to predict diseases that would occur later in their lives. Almost the same number of people said "no" as said "yes".
In addition, unless test results of genetic testing can lead to direct medical benefits, experts advise parents to avoid making this choice for their children. For most adult-onset conditions, knowing a child's genetic testing status will not affect the course of the disease or its treatment. The decision to have a genetic testing should be left to the individual, at a time when he or she is mature enough to weigh the options and handle the results.
Because the genetic testing issues are so complex and so new, and the consequences so profound, the decision to have a genetic testing deserves careful preparation and thought. One pivotal consideration concerns whether or not any action might be prompted by the test. If the test is positive in genetic testing, are there opportunities for prevention or early detection?
The decision for genetic testing is especially wrenching for persons confronted with a disease that can be neither prevented nor cured. In one such situation, Huntington's disease, many families initially expressed interest in being tested; however, when the genetic testing test actually became available, just a tiny fraction chose to go ahead with it.
The story may be different for breast and colon cancer, where there are opportunities for prevention, early detection, and treatment. Indeed, early experience from a breast cancer gene research program indicated that most of the people who had donated samples for DNA testing chose to learn the results.

 WHAT ARE TODAY’S OPTIONS FOR GENETIC TESTING?

We already know a lot about cancer prevention and early detection in genetic testing, and we don't need to wait for a genetic testing to put this information to good use. Regular checkups by the doctor - including mammography, prostate exams, skin exams, or Pap tests as appropriate - coupled with a healthy lifestyle are important for everyone. So is avoiding known causes of cancer: cigarette smoke, too much sunlight, and unnecessary radiation. Persons who have a family history of cancer should be especially conscientious about observing these precautions, and they should make sure their doctor is aware of their family history. People with a very strong family history - a number of close relatives who have had cancer, especially if it occurred at a young age and in more than one generation - may want to schedule more frequent checkups and begin them in their twenties or thirties. Prophylactic surgery is an option in genetic testing, although persons considering it should realize that it brings no guarantee that cancer won't occur. Another option of genetic testing is to contact one of the research programs now getting under way.
It isn't necessary, though, for genetic testing to arrive on the scene to give serious thought to the idea. If a genetic testing were available, would you want to have it? Would you want your family to be tested? What actions would you be prepared to take? And what should society be doing about the issues of privacy and discrimination? The present moment, when genes are being discovered but before tests become widely available, offers a small window of opportunity to prepare for the future.

Author : Anuradha Panda.