Because mutations in BRCA1 and BRCA2 in women with breast cancer are associated with an increased risk of ovarian cancer, analysis of these genes should be considered for women diagnosed with breast cancer who have a high probability of carrying a mutation according to the statistical model developed with these data.

IntrodutionThe breast cancer 1 (BRCA1) genel2 has recently been cloned and sequenced.3'4 Many BRCA1 mutations have been characterized in families previously shown to have a chromosome 17q-linked susceptibility to breast cancer.-7 The large size of BRCA1, the large number of mutations, the need to distinguish polymorphisms from pathogenic mutations, and the existence of other loci for hereditary breast cancer susceptibility (e.g., BRCA2)8 will complicate testing. Nevertheless, because of the salience of the breast cancer threat, these technical problems are likely to be solved, raising the following question: Will women choose to have a test to identify BRCA1 mutations if such a test becomes available? We conducted a survey to determine women's receptivity to this type of testing. MethodsThe subjects surveyed were awaiting medical services in one of two settings, a radiologic practice specializing in the diagnosis of breast disease or a general obstetrics/gynecology group practice. One of the investigators, a female physician who was not a member of either practice, approached patients waiting to be seen and asked them to complete a questionnaire. The questions were preceded by the following statement: "A blood test identifying certain women as having a gene associated with a high risk of developing breast cancer in her lifetime is likely to be available in the next few years. In order to decide whether women will use such a test, we would appreciate your answering the following questions." Questions assessing attitudes involved fivepoint (Likert) response scales (e.g., strongly disagree, disagree somewhat, neither agree nor disagree, agree somewhat, or strongly agree). ResultsThe rate of participation was very high; 95% of the obstetrics/gynecology patients and 98% of the mammography patients agreed to participate. Questionnaires were completed by 484 mammography patients, 343 gynecology patients, and 155 obstetrical patients.Of the women surveyed, 31.4% of the mammography patients and 22.5% of the obstetrics/gynecology patients had at least one affected first-or second-degree relative. Patients having mammography were significantly more likely than patients visiting their obstetrician-gynecologist to have an affected first-degree relative (83% vs 29%; P < .001 by chi-square test).Patient responses to the offer of testing are summarized in Table 1. Reasons given for accepting the test included "to take extra precautions if the risk were high" (59%) and "for reassurance that the risk was low" (38%). Predictors of test acceptance are given in Table 2. Women declining the test (5.9% of the total) reported that they were content with what they were currently doing about the risk of breast cancer, did not like to have their blood drawn, or were made too anxious by thinking about taking the test.Women were willing to pay more for the test if they were older (P < .001), if they were having mammography regularly (P < .001), if they were very concerned about getting breast cancer (P < .001), if they believed that mammogr...

The principal Mendelian disorders predisposing to colorectal cancer are familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC). FAP is due to mutations in the APC gene. HNPCC is due to a mutation in one of at least five mismatch repair genes. Identification of individuals with these conditions is important because colon cancer will occur in approximately 80% and onset is early. For FAP, protein truncation testing will identify the vast majority of mutations. For HNPCC, 80%-95% can be identified by microsatellite instability testing. A current U.S. study reports that 12% of consecutive colorectal cancers have high microsatellite instability and that, of this 12%, 25% have detectable mutations of MLH1, MSH2, or MSH6. Potential benefits of identification include improved compliance with recommended surveillance, early detection of polyps, reduction in cancer mortality, offering of testing to relatives, and reassurance for relatives found to be negative with attendant savings in the time and expense of surveillance.

The most common inherited syndrome in man predisposing to neoplasia is neurofibromatosis-1 (von Recklinghausen disease) (NF1). We investigated the hypothesis that affected individuals carry a single inactive allele at the NF1 locus in the germline and that a tumor arises from a cell in a susceptible tissue in which the remaining normal allele has been lost or inactivated. DNA from tumor and nontumor tissue from 27 NF1 patients was analyzed with three markers closely linked to the NF1 locus and two additional markers from chromosome 17. No loss of heterozygosity was observed in neurofibromas, plexiform or not. For other tumor types analyzed, seven of 14 showed a loss. A loss of heterozygosity was observed in six of 11 of the malignant peripheral nerve tumors analyzed. Of the seven malignancies demonstrating a loss, five involved a neurofibrosarcoma. These findings suggest that the pathogenesis of neurofibrosarcoma in NF1 involves a deficiency of the NF1 gene product. In any given patient, loss of heterozygosity was detected at some marker loci but not others. Thus the mutations demonstrated in these tumors comprise a set of overlapping mutations, which may facilitate more precise localization of the NF1 gene.

The cloning of the CFTR gene has made it technically possible to avert the unwanted birth of a child with cystic fibrosis (CF). Several large trials offering prenatal CF carrier screening suggest that such screening is practical and that identified carriers generally use the information obtained. Therefore, a critical question is whether the cost of such screening is justified. Decision analysis was performed that used information about choices that pregnant women were observed to make at each stage in the Rochester prenatal carrier-screening trial. The cost of screening per CF birth voluntarily averted was estimated to be $1,320,000-$1,400,000. However, the lifetime medical cost of the care of a CF child in today's dollars was estimated to be slightly>$1,000,000. Therefore, despite both the high cost of carrier testing and the relative infrequency of CF conceptions in the general population, the averted medical-care cost resulting from choices freely made are estimated to offset approximately 74%-78% of the costs of a screening program. At present, if it is assumed that a pregnancy terminated because of CF is replaced, the marginal cost for prenatal CF carrier screening is estimated to be $8,290 per quality-adjusted life-year. This value compares favorably with that of many accepted medical services. The cost of prenatal CF carrier screening could fall to equal the averted costs of CF patient care if the cost of carrier testing were to fall to $100.