Reported by Nick Zagorski
February 23, 2005

It can be difficult enough to hear a doctor tell you that you have been diagnosed with cancer, but how would someone react if a doctor told them that while they might be healthy now, they are likely to have cancer in the future?

Most cancers arise from spontaneous DNA mutations that accumulate in a cell over time, whether due to environmental exposure, lifestyle factors, or random chance. Individual cells will pick up different genetic mutations, and in some cases a cell can acquire the right --or wrong, as the case may be-- combination of mutations to trigger carcinogenesis.

However, approximately 5-10 percent of all cancers are hereditary, or familial. These cancers arise in certain individuals that carry a defective gene or genes which they inherited from their parents and could then pass on to their offspring. Since they have a copy of this defective gene in every cell in their body, carriers of familial cancer genes are far more likely to develop cancer. Joyce Seldon, a certified genetic counselor at UCLA’s Jonsson Comprehensive Cancer Center, points out, though, "that unlike other hereditary diseases such as cystic fibrosis, inheriting one of these genes does not automatically mean that a person will get cancer."

Still, the increased cancer risk these individuals face is tremendous. For example, women who carry a defective BRCA1 gene, which is critical for repairing mutated DNA, have as much as an 85 percent risk of developing breast cancer and a 65 percent risk for ovarian cancer; they also have an increased risk of developing secondary cancers after they get breast or ovarian cancer, and generally develop cancer at an earlier age than non-carriers.

"Normal recommendations call for regular mammography screenings beginning at age 40," says Jeffrey Weitzel, M.D, City of Hope Comprehensive Cancer Center, "but this is often too late for BRCA1 carriers; they should begin surveillance at age 25 instead of 40. So it is important to understand who is at risk."

Fortunately, advances in genetics make it possible to identify some of those people at increased risk. In addition to BRCA1, susceptibility genes have been identified for numerous cancers. For other cancers exact genes aren't known, but susceptibility loci, or the general location on a chromosome, have been identified. NCI researchers have even identified a susceptibility locus for lung cancer, which has traditionally been viewed primarily as a lifestyle disease. Because affected people have these mutations in all of their cells, genetic tests of blood samples can look at the genes, or markers near the genes, to identify people who may have an increased risk of cancer.

But while genetic testing can be done, a more pertinent issue is whether it should be done, and how the results should be used. Positive results can be psychologically overwhelming, and create difficult long-term decisions. "Right now there is no effective early detection for ovarian cancer," says Seldon, "which is why it’s known as the silent killer. BRCA1 carriers, especially those with a family history of ovarian cancer, may have to choose between risking cancer or removing their ovaries and no longer being able to have children."

"The results of genetic testing affect whole families and not just the individual," Seldon adds. Relatives discover they may also carry an increased risk, while parents may worry whether they have passed the mutant gene on to their children. For Seldon, and other genetic counselors, they have the sometimes difficult job of presenting genetic test results to patients, and they provide both comfort and professional guidance as the individual explores all possible options.

Genetic testing, regardless of whether it turns out positive, negative, or even inconclusive, brings up some ethical issues as well. “There’s the potential issue of physician liability,” says Weitzel, “in cases where they fail to diagnose cancer predisposition, and no screening is offered, and then that person goes on to get cancer.” Weitzel believes physicians need to be more proactive in assessing individuals that have a strong chance to be carriers and recommending testing and counseling.

A bigger dilemma is how to incorporate genetic testing with health insurance. " Many people fear that a positive result will make them a target of genetic discrimination if the insurance finds out," says Dr. Weitzel. “ However, most patients and their physicians are unaware of existing protective legislation or the lack of problems identified to date." The confidentiality of the patient is a two-way street, however, since insurance companies can also fear that individuals may take advantage of their private knowledge of their increased risk. Genetic tests are also expensive, ("Although it is far cheaper to get this test than to get cancer," Seldon points out), which brings up the question of whether insurance should cover a procedure that may not qualify as preventive or therapeutic. “This is complicated on all sides of the issue,” says Weitzel, "but we don’t want a system that hinders people for trying to prevent cancer."

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