Thanks to advances in genetic medicine, DNA tests can now determine your risk for some cancers, giving doctors powerful fortune-telling tools for prevention and treatment.
gene on chromosome 9).
Interest in genetic tests for cancer risk in particular is enormous. Cancer is the second leading cause of death in the United States (after heart disease) and will strike more than 550,000 people this year alone, according to the American Cancer Society. As in Hensons case, genetic testing could alert those who have no family history of the disease and could revolutionize health care aimed at cancer prevention.
Were at the beginning of the age when we can predict for cancer risk, says Peter Jones, director of the USC/ Norris Comprehensive Cancer Center. Theres enormous interest in this field, and it is an increasing part of our work here. This is something that could really make a difference.
Despite great interest, no one is expecting an enormous rush to testing. For one thing, the tests have raised a host of moral, ethical and legal questions that will take years to sort out. Until test-result privacy can be guaranteed, many Americans fear taking a genetic test could have negative consequences on employment (because health insurance is primarily obtained through a job), as well as on health- and life-insurance costs. Some fear it may lead to sweeping changes in insurance coverage: based on genetic tests, will insurers demand (and only pay for) preventive measures, not treatment of the disease itself?
Privacy isnt the only impediment. By current estimates, each individual carries about five mutations that predispose him or her to a lethal disease. Almost everyone, therefore, would have to deal with some bad news if tested and not everyone wants that headache.
And then there is the decision about how to actually use the results. Some, like Henson, take aggressive preventive action, while others find themselves deeply conflicted. In Hensons own family, news of her genetic predisposition to breast cancer prompted two of her four sisters to get tested themselves; the other two didnt want to know. One sisters test has come back positive for BRCA-2, and she is now struggling with her options.
We are still years away from having a standardized test to determine each individuals cancer risk, says Jones, a biochemist and molecular biologist in the Keck School of Medicine of USC.
Genetic testing for cancer predisposition is still a fairly new science. It dates back to 1982, when a deletion of part of chromosome 3 was first observed in cancerous cells from certain lung tumors. The much-ballyhooed discovery in the early 1990s of BRCA-1 and BRCA-2 led to a prediction that, with the deciphering of the human genome, we would soon pinpoint the specific rare mutations that are the harbingers of all cancers.
This hope was bolstered by the discovery, in the mid-1990s, of mutations on p53 a tumor-suppressor gene (one that naturally blocks the formation of tumors). The mutations are found in most tumor types, and p53 has been hailed a key player in the complex network of molecular events leading to tumor formation. A person inheriting only one functional copy of the p53 gene a rare congenital deficiency called Li-Fraumeni syndrome is predisposed to cancer and usually develops several independent tumors in early adulthood.
Scientists are coming to realize, however, that most cancer is not caused by one easily identified mutation.
We know there are two kinds of genetic approaches to the bodys tendency toward cancer, says Jones. The first involves rare genetic mutations that signal a fair probability that the carrier will develop cancer.
BRCA-1 and BRCA-2 fall into this group. In certain defined cases, those tests can be very, very helpful, Jones says.
But scientists have also discovered other genes with more common small bits called polymorphisms that in and of themselves dont lead to cancer, but do contribute to making conditions ripe for the disease.
Researchers are trying to develop [tests for] these genes, but were still quite a ways away, Jones says. Were just beginning to work on it.
What that means for patients, according to USC/Norris genetic counselor Alvarado, is that at present theres no easy answer to the question of any individuals risk for cancer.
And for researchers, it means wading through enormous amounts of genetic data in search of specific clues.
One such molecular sleuth is Heinz-Josef Lenz, USC/Norris scientific director of cancer genetics. Not long ago, Lenz and his colleagues identified a polymorphism that might tip them off to who is and isnt likely to get colon cancer at an early age.
Lenz and his team examined a gene thats related to a protein in the body called manganese superoxide dismutase, or MnSOD. This protein is one of the bodys key chemical fighters against oxidative stress a known factor in cancer and other diseases.
If your MnSOD gene works well, the MnSOD protein your body produces can effectively scavenge and neutralize oxidative radicals that damage human cells.
But if you have a certain polymorphism of this gene, your body produces a slightly different kind of MnSOD that researchers believe packs a less protective punch. People with this polymorphism may not be as shielded from cellular damage as others, and may be more likely to get colon cancer at a young age, says Lenz.
The MnSOD gene isnt the only one responsible for early-onset colon cancer, however. Lenzs group also is exploring the role of the XRCCI gene, a crucial player in DNA repair. The researchers are looking at the frequency and significance of XRCCI polymorphisms and are gathering data to show its potential role in colon cancer.
The gene appears to predict resistance to chemotherapy, too. By testing for an XRCCI polymorphism in colon cancer patients, doctors may soon know in advance that a particular tumor would resist certain drugs, and opt for other, more potent drugs instead.
Photo by S. Peter Lopez