WASHINGTON _ Biotechnology companies that see dollar signsflashing with each discovery of a new cancer gene could do more harmthan good if they rush to the marketplace, according to leadinggeneticists. The entrepreneurial drive that will create the gene testingand screening techniques of the future must, at present, be kept incheck.Researchers here at a National Cancer Institute workshop on hereditarybreast, ovarian and colon cancer stressed that there is much more tolearn before genetic testing and screening services should be marketedby companies and made available to the public."We will not enjoy the benefits of advances in genetics if we don'thave companies taking the discoveries and turning them into products,"Francis Collins, director of the National Institutes of Health's (NIH)Human Genome Project told BioWorld."But there is a potential dilemma here between the desire of a companyto establish a market and get a share of it as quickly as possible and theneed to very thoughtfully consider whether we have addressedquestions about the potential harm genetic testing could do."Over the past year, in an astounding succession of genetic triumphs,researchers have located a number of relatively common hereditarycancer risk genes. As many as 30 percent of people with colon cancercarry a mutation of a gene called hMLH1, while roughly 10 percentcarry a mutation of the MSH2 gene. Approximately 5 percent ofwomen with breast cancer inherit a mutated version of a gene calledBRCA1. Individuals that carry these mutated genes face an extremelyhigh risk of developing cancer.Out Of The Bag"Now that we've discovered two colon cancer genes there is aninstinctive appeal to begin translating the research into patient care andtesting," Frederick Li, a geneticist from Harvard Medical School, toldthe audience at Wednesday's workshop. "The colon cancer gene is outof the bag. If a test is available, it will be difficult for physicians not tooffer it to patients who ask."Li said that widespread press coverage of the recent discoveries has putpressure on researchers to make genetic screening immediatelyavailable to both high-risk families and even to the general population.In addition, he said that companies are chomping at the bit tocommercialize the discoveries.But Li argued that, at present, only a small number of patients canmeaningfully interpret results from genetic testing. Li calculated thatscreening a random sample of 10,000 individuals (average risk fordisease: 1 in 200) for colon cancer, would produce a positive "hit rate"for the suspect gene of only 4 percent. Screening a group of 10,000individuals at higher risk (average risk for disease: 1 in 20) wouldproduce only a 32 percent hit rate, according to Li.Li said that the benefits of genetic screening for high-risk individualsmay seem obvious: family members who test negative learn that theirrisk for cancer is greatly decreased, freeing them to plan careers andfamilies while those who test positive can pursue preventive medicalstrategies that could save their lives, avoid environmental carcinogensthat might exacerbate their condition, engage in pre-natal testing fortheir offspring, and gain a sense of empowerment from knowledge oftheir condition.Not All Good NewsBut there are drawbacks to genetic testing. Non-carriers can sufferfrom survivor guilt and families that were once united become dividedalong genetic lines. In addition, tests can be wrong. For carriers, theknowledge of their genetic defect can cause confusion, loss ofemployment and/or medical insurance, societal or familystigmatization, anxiety and depression. Genetic testing withoutcounseling to aid patients in handling the information may wreakhavoc in society.An editorial on the subject of DNA testing for presymptomaticidentification of cancer risk appeared in the March 9, 1994 edition ofthe Journal of the American Medical Association (JAMA). Li said heagreed with the authors _ 15 geneticists who comprise the NationalAdvisory Council for Human Genome Research _ that it is prematureto offer genetic testing to either high-risk families or to the generalpopulation as part of general medical practice.The JAMA commentary said that critical unanswered questions mustbe addressed before the genie of genetic testing is let out of the lamp:y How many different mutations of the genes (such as MSH2 andBRCA1) will be found, what are their frequencies and what is the riskof cancer associated with each?y What are the technical and laboratory issues associated with detectionof mutations in these genes, what frequency of false-negative and false-positive results will occur and how can quality control of testing beassured?y How effective are interventions to prevent cancer morbidity andmortality in high-risk families and in the general population?y How can people be educated about the complexities of DNA testingand how can effective, culturally sensitive, nondirective counseling beoffered about profoundly wrenching issues?y How will the possibility of genetic discrimination against high-riskindividuals be avoided?Don't Offer Testing, YetThe JAMA editorial concludes that until these questions are answered,genetic testing should not be offered outside a carefully monitoredresearch environment. "We can do it (genetic testing) technically, butwe don't yet know how best to do it," cautioned Li.One biotechnology company, is already offering "molecularsusceptibility" testing services to clinicians. OncorMed, a subsidiary ofGaithersburg, Md.-based Oncor Inc., provides colon cancersusceptibility testing and p53 mutation analysis to physicians workingunder Institutional Review Board- approved clinical protocols.The company does not need FDA approval to offer these medicalevaluation services to investigators because they manufacture their ownreagents and use their own methodologies, according to OncorMed'spresident and chief operating officer, Doug Dolginow. They operateunder the same guidelines as any laboratory.Dolginow said his company's activities comply with the sentimentsexpressed in the JAMA editorial but added that even as more questionsabout genetic testing are answered, the concept may remaincontroversial. "People still argue about whether chest X-rays arenecessary or useful," Dolginow told BioWorld. "There is continueddisagreement about the usefulness of almost every aspect of medicine."

-- Lisa Piercey Washington Editor

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