Progress of a Comprehensive Familial Cancer Genetic Counseling Program in the Era of BRCA1 and BRCA2

BRCA1 and BRCA2 mutation carriers have an increased risk of developing breast and/or ovarian cancer. Technical advances in genetic testing have increased the need for genetic counseling services; therefore, we have developed a counseling program for these individuals. The purpose of this study is to characterize this population, assess level of interest in genetic testing, and evaluate our program over a 5-year period. Our Familial Cancer Genetic Counseling Program was established in November, 1994. Information was collected prospectively, with comprehensive evaluation including complete pedigree, risk assessment, and counseling by a genetic counselor, geneticist, and oncologist. Data were collected on risk level, and subsequent recommendations for screening and/or genetic testing. There were 824 contacts recorded from November, 1994, through August, 1999. To date, 162 families have undergone comprehensive genetic evaluation and counseling. 90 (56%) were seen for a concerning family history and 72 (44%) were seen due to a personal history of malignancy. The majority of families had a significant level of risk with 126 (78%) families having two and 70 (43%) families having three affected first-degree relatives. Of the 162 families who received full counseling, 125 (77%) met criteria to recommend BRCA1/BRCA2 genetic testing. At this time, 30 of the 162 (18%) have had genetic testing. A brief phone contact or clinic visit is useful to screen individuals so that counseling can be directed toward truly high-risk families. In our program, the majority of families counseled were eligible for BRCA1/BRCA2 testing, but only 18% have elected to proceed at this time.     

Ethical and legal dilemmas arising during predictive testing for adult-onset disease: the experience of Huntington disease.

The goal of predictive testing is to modify the risk for currently healthy individuals to develop a genetic disease in the future. Such testing using polymorphic DNA markers has had major application in Huntington disease. The Canadian Collaborative Study of Predictive Testing for Huntington Disease has been guided by major principles of medical ethics, including autonomy, beneficence, confidentiality, and justice. Numerous ethical and legal dilemmas have arisen in this program, challenging these principles and occasionally casting them into conflict. The present report describes these dilemmas and offers our approach to resolving them. These issues will have relevance to predictive-testing programs for other adult-onset disorders.     

Parental attitudes toward genetic testing for pediatric deafness

Recent molecular genetic advances have resulted in genetic testing becoming an option for deaf individuals and their families. However, there is little information about the interest in such testing. To investigate this issue, parents with normal hearing who have one or more deaf children were surveyed about their attitudes toward diagnostic, carrier, and prenatal genetic testing for deafness. This population was chosen because it represents the majority of individuals who are encountered in clinical practice, given that 90%-95% of deaf individuals are born to persons with normal hearing. Of 328 surveys distributed, 96 were completed and returned. Of the respondents, 96% recorded a positive attitude toward genetic testing for deafness, including prenatal testing, although none would use this information to terminate an affected pregnancy. All respondents had a poor understanding of genetics, with 98% both incorrectly estimating the recurrence risk of deafness and misunderstanding the concept of inheritance. Notably, these findings were similar in the group who had had genetic testing for their children and in the group who had not, suggesting either that the parents who received genetic testing did not receive genetic counseling or that the counseling was not effective. On the basis of these results, it was concluded that this population is interested in the use of genetic testing and that testing should not be done without first providing formal genetic counseling. Appropriate counseling can help parents to understand the risks, benefits, and limitations of genetic testing.     

Attitudes toward genetic testing for cancer risk after genetic counseling and decision support: a qualitative comparison between hereditary cancer types

This study aimed to qualitatively assess individuals' attitudes toward genetic testing for cancer risk after genetic counseling and decision support. As part of a larger study, 78 women considering genetic testing for hereditary breast/ovarian cancer (HBOC) risk and 22 individuals considering genetic testing for hereditary nonpolyposis colorectal cancer (HNPCC) completed an open-ended table of their perceived pros and cons of genetic testing. The most frequently reported pros were "to help manage my risk of developing cancer," "to help my family," and "to know my cancer risk." With regards to risk management, the HBOC group perceived genetic testing as most helpful in informing their general risk management practices, while the HN-PCC group focused on the potential to clarify their need for bowel cancer screening, suggesting that patients' perceptions of the benefits of genetic testing may differ across cancer syndromes. Individuals in both groups expressed concern about the potential psychological impact of genetic testing. We also found that some affected individuals may not fully comprehend the meaning of their potential test results. Eliciting patients' perceived pros and cons during genetic counseling is likely to be a valuable tool for improving patient care. This data also provides an improved evidence base for the development of patient education tools.     

Attitudes toward genetic testing in patients at risk for HNPCC/FAP and the German population

Adequate knowledge regarding hereditary diseases and genetics, as well as personal attitudes toward gene tests, are major determinants of optimal utilization of genetic testing. In the present study, we aimed to explore the general attitudes toward genetic testing in a sample representative of the German general population (n = 2,076) and to compare the attitudes of persons at risk for hereditary non-polyposis colorectal cancer/familial adenomatous polyposis (HNPCC/FAP) (n = 36) who had attended a university genetic counseling service, with a matched general population sample. We administered a subset of a questionnaire previously used in a Finnish study (Jallinoja et al., 1998). The 12 statements pertain to approval, disapproval, and concern for genetic testing. Overall, the results reveal high approval of genetic testing in the German population and in at-risk persons. In accordance with other studies, we find that the attitudes of individuals for whom hereditary disease is a salient issue of personal relevance and the attitudes of the general public are very similar. Only a few significant differences between these two samples emerged, indicating that at-risk persons hold a more favourable view of the testing. One intriguing finding was the high rate of "don't know" responses, especially in the general population sample. Compared to results from Finland, approval of genetic testing is lower in the German population, and endorsement of "don't knows" is remarkably higher. We argue for increased attention to the issue of attitude change after genetic counseling and for the need of comparative cross-cultural research on attitudes toward gene technology.     

Simultaneous interdisciplinary counseling in German breast/ovarian cancer families: first experiences with patient perceptions, surveillance behavior and acceptance of genetic testing

As part of a multicenter study supported by the German Mildred Scheel foundation we have established an interdisciplinary counseling setting for members of breast and/or ovarian cancer families. We offer simultaneous counseling by a team consisting of a geneticist, a gynecologist and a psycho-oncologist. Here we describe our counseling protocol and our first short-term experience with this interdisciplinary approach. Preliminary data on patient perceptions and behaviors in the context of DNA testing are reported. Overall, our counseling approach was perceived as beneficial both by the counselors and the consultants. A marked overestimation of the risk to develop breast and/or ovarian cancer was noted in the group of unaffected individuals from medium to low risk breast cancer families in contrast to an appropriate risk perception in members from high risk families. All participants shared many of the same expectations about genetic testing and counseling and appeared to base their decision-making about testing on the risk classification given by the genetic counselor. The reported participation in gynecological cancer prevention programs was high in all families at risk, but was less sufficient in unaffected as compared to affected persons. Although current data on BRCA1/BRCA2 mutation analyses render testing in medium to low risk individuals questionable, our findings emphasize the importance of genetic counseling and education in all risk categories of breast and/or ovarian cancer families.     

Genetic testing and risk assessment for spinal muscular atrophy (SMA)

Spinal muscular atrophy (SMA) is one of the most common autosomal recessive diseases, affecting approximately 1 in 10,000 live births, and with a carrier frequency of approximately 1 in 50. Because of gene deletion or conversion, SMN1 exon 7 is homozygously absent in approximately 94% of patients with clinically typical SMA. Approximately 30 small intragenic SMN1 mutations have also been described. These mutations are present in many of the approximately 6% of SMA patients who do not lack both copies of SMN1, whereas SMA of other patients without a homozygous absence of SMN1 is unrelated to SMN1. A commonly used polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) assay can be used to detect a homozygous absence of SMN1 exon 7. SMN gene dosage analyses, which can determine the copy numbers of SMN1 and SMN2 (an SMN1 homolog and a modifier for SMA), have been developed for SMA carrier testing and to confirm that SMN1 is heterozygously absent in symptomatic individuals who do not lack both copies of SMN1. In conjunction with SMN gene dosage analysis, linkage analysis remains an important component of SMA genetic testing in certain circumstances. Genetic risk assessment is an essential and integral component of SMA genetic testing and impacts genetic counseling both before and after genetic testing is performed. Comprehensive SMA genetic testing, comprising PCR-RFLP assay, SMN gene dosage analysis, and linkage analysis, combined with appropriate genetic risk assessment and genetic counseling, offers the most complete evaluation of SMA patients and their families at this time. New technologies, such as haploid analysis techniques, may be widely available in the future.     

Screening for 185delAG in the Ashkenazim.

A study was initiated to assess interest, educational effectiveness, and implications of genetic testing for the common BRCA1 mutation, 185delAG, in the Ashkenazim. Of 333 individuals who attended group sessions, 309 (92%) participated in the study. Participants were categorized as having negative family history (67%), positive family history (defined, by a relaxed criterion, as one first-degree relative or two second-degree relatives with breast [premenopausal] or ovarian cancer) (22%), positive personal history (7%), and both positive personal history and positive family history (4%). Group education was effective, as shown by the improvement in participant scores from pre- to posteducation tests. For the 289 individuals (94%) who requested testing, the major reasons included concern for their own risk, concern for the risk of their children, and desire to learn about surveillance options. The most common reason given by participants who declined testing was concern about health insurance. Six participants found to be heterozygous for the 185delAG mutation received results and were offered genetic counseling. Participants had consented for additional testing without receiving results and were screened for the 6174delT mutation in BRCA2, and seven were found to be positive. All identified carriers reported at least one first- or second-degree relative with a history of breast or ovarian cancer, although they did not all meet our study criteria for positive family history. Given these outcomes, we conclude that screening for breast and ovarian cancer susceptibility is most appropriate for individuals with a positive personal or positive family cancer history. We propose a guideline for future studies designed to identify individuals who may benefit from genetic testing for inherited breast and ovarian cancer.     

Ziele und Grenzen der Quantifizierung genetischer Risiken

This present article deals with the question of how meaningful statistical risk assessments in genetic counseling may be for the decision-making process of individuals who ask for genetic advice. Even in some Mendelian diseases and generally in the case of multifactorial diseases it is not satisfactory to provide an a priori risk for all affected families. The question of whether a given person or his or her future children may develop the disease in question with severe, possibly untreatable symptoms may largely depend on individual circumstances. Accordingly, the inclusion of such circumstances in the assessment of an individual’s a posteriori risk may largely deviate upwards or downwards from this a priori risk. Currently, the lack of such data often prevents the quantification of an individual a posteriori risk; it is, however, obvious that individual risk assessment will play an increasing role in future genetic counseling. Besides a better understanding of individual environmental influences our growing insight into the impact of epigenetic changes will enforce a re-evaluation of individual risks. Epigenetic changes acquired during fetal development or early childhood may lead to lasting physiological changes and, accordingly, may significantly affect the risk of an individual to develop a certain disease during his or her later life. Due to the complexity of genetic and epigenetic networks it is as inappropriate to categorize mutated genes or alleles which increase the risk for a certain disease as “bad” or “sick” genes as it is to consider genes with apparently health-promoting properties as “good” or “healthy” genes. Such rhetoric may foster feelings of either guilt or superiority in individuals and may have an even more politically dangerous impact by encouraging neo-eugenic thinking. In contrast, the goal of non-directive genetic counseling is to provide individuals seeking advice with reliable information which helps them arrive at a personal decision. Given their personal circumstances this decision should be ethically acceptable and realistically allow them to cope with their problem in their future lives. As seen in cases of Mendelian diseases, such as sickle cell anemia or thalassemias, heterozygous carriers may have selective advantages, in this particular case a natural resistance against Malaria tropica. This example demonstrates that a genetic burden may not have only disadvantages but also advantages for the health of a whole population. This consideration may hold for many alleles which have been present in the gene pool of a population for many generations, although they contribute to a genetic predisposition for a multifactorial disease. In debates about the heritability of a given trait, the heritability coefficient has often been used as an argument for and against the predominant impact of genes on the trait in question. The authors wish to remind their readers that this coefficient reflects the genetic variation measured in a given population divided by the variation of all possible parameters which affect the phenotypic trait. It neither gives an answer about the absolute influence of genes and other factors on this trait nor does it provide information about how unforeseen changes in the environment may affect the heritability of the trait in the future. Contrary to a common misunderstanding in public discussion this coefficient does not allow any conclusion on the interaction of genetic, epigenetic and environmental factors involved in the development of the trait in question in an individual. Finally, in the closing section the authors highlight the opportunities of risk-adapted disease prevention.     

Comprehensive genetic counseling for families at risk for HNPCC: impact on distress and perceptions

The aim of the study was to explore distress and health beliefs before and after comprehensive interdisciplinary counseling in families at risk for hereditary non-polyposis colorectal cancer (HNPCC). Results reported here were derived from a consecutive sample of 65 counselees [31 patients with colorectal cancer (CRC) and 34 unaffected at-risk persons] who participated in interdisciplinary counseling provided by human geneticists, surgeons, and psycho-oncologists before genetic testing. Data were collected from self-administered questionnaires before, as well as 4-6 weeks after, counseling. Distress and perceptions specific to HNPCC were assessed at both timepoints using standardized as well as author-derived instruments. Distress declined after counseling, as did worries related to HNPCC. An increase was found in personal belief in control of cancer risk, for instance, in the perceived efficacy of early detection of CRC. We also observed a trend toward greater anticipated ability to cope with a positive gene test after counseling. Changes after counseling were generally more pronounced for persons at risk, as compared to patients with cancer. The decrease in distress was partly attributable to an increase in personal self-confidence. One-third of the sample reported enhanced communication specific to hereditary disease within the family after counseling. A substantial minority, however, said they experienced increased worry and physical symptoms after counseling. Overall, counselees demonstrated less stress and perceived cancer threat as well as enhanced beliefs regarding personal control over cancer, suggesting an overall beneficial impact of comprehensive counseling. Further research is needed to identify those individuals most at risk for increased fear and worry related to HNPCC so that they may be most appropriately counseled.     

Does genetic counseling have any impact on management of breast cancer risk?

Despite there being an increasing literature on the impact of cancer genetic counseling on risk perception and mental health, there is a lack of data describing impact on risk management. Genetic counseling and testing for cancer predisposition genes aims to improve the future health of those at high risk through appropriate surveillance and screening. However, management of breast cancer risk in women with a family history of this disease is an area of controversy. Counseling services may recommend specific risk management options to women, who then rely on their local screening service to make provision. This study investigated the impact of genetic counseling on management of breast cancer risk in women attending Cancer Family Clinics. A total of 293 women attending four genetic clinics were enrolled. Rates of breast self-examination, clinical breast examination, mammography, biopsy, detected cancers, and other screenings were documented. Participants' perceived benefits and barriers to mammography were assessed along with cancer worry. Results show that rates of mammography, clinical breast examination, and breast self-examination were increased following clinic attendance (p < 0.001). Women in the under 35 age-group had limited access to screening. Rates for biopsy and detected cancers were low. Women reported positive attitudes to mammography, with few reported barriers. Contrary to previous studies, there was no evidence that anxiety about breast cancer impedes uptake of health surveillance methods. Genetic counseling had a positive impact on management of breast cancer risk. Whether this translates into future health gains remains to be established.     

Impact of genetic testing for breast-ovarian cancer susceptibility

Previously, we have reported a clinical trial in which any woman in a defined geographic region who had a qualifying family history and who was referred by her physician or who was identified through a regional cancer registry was offered free genetic counseling, BRCA testing, and recommendations based on test results. Each family was represented by one affected and one unaffected person. Of the 87 families actually tested, 13 were found to have deleterious mutations. To assess the impact of the counseling and testing process, we contacted the tested individuals 1 month and 1 year after receiving the test result and those with an abnormal test result after 4 years. Index subjects, we found, differed significantly from relatives. Before coming for counseling, index subjects perceived both their general health and emotional health as worse than did their relatives. After counseling and testing, index subjects continue to worry more about breast cancer than do relatives. Affected subjects, we found, differed significantly from unaffected subjects. Before counseling, affected subjects knew more about breast cancer, perceived their general health as poorer, and reported greater adherence to recommended breast cancer surveillance than did unaffected subjects. After counseling and testing, affected subjects were less satisfied than unaffected subjects with having been tested. This study indicates that the group most prone to distress by cancer risk genetic counseling and testing is not the recruited relatives, nor even those affected with cancer, but rather the index patients themselves. The index patients, i.e., the ones who want the risk information most, appear to undergo the most stress in obtaining it.     

Factors Motivating Individuals to Consider Genetic Testing for Type 2 Diabetes Risk Prediction

The purpose of this study was to identify attitudes and perceptions of willingness to participate in genetic testing for type 2 diabetes (T2D) risk prediction in the general population. Adults (n = 598) were surveyed on attitudes about utilizing genetic testing to predict future risk of T2D. Participants were recruited from public libraries (53%), online registry (37%) and a safety net hospital emergency department (10%). Respondents were 37±11 years old, primarily White (54%), female (69%), college educated (46%), with an annual income ≥$25,000 (56%). Half of participants were interested in genetic testing for T2D (52%) and 81% agreed/strongly agreed genetic testing should be available to the public. Only 57% of individuals knew T2D is preventable. A multivariate model to predict interest in genetic testing was adjusted for age, gender, recruitment location and BMI; significant predictors were motivation (high perceived personal risk of T2D [OR = 4.38 (1.76, 10.9)]; family history [OR = 2.56 (1.46, 4.48)]; desire to know risk prior to disease onset [OR = 3.25 (1.94, 5.42)]; and knowing T2D is preventable [OR = 2.11 (1.24, 3.60)], intention (if the cost is free [OR = 10.2 (4.27, 24.6)]; and learning T2D is preventable [OR = 5.18 (1.95, 13.7)]) and trust of genetic testing results [OR = 0.03 (0.003, 0.30)]. Individuals are interested in genetic testing for T2D risk which offers unique information that is personalized. Financial accessibility, validity of the test and availability of diabetes prevention programs were identified as predictors of interest in T2D testing.     

Factors determining dissemination of results and uptake of genetic testing in families with known BRCA1/2 mutations

BACKGROUND: Uptake of genetic testing remains low, even in families with known BRCA1 and BRCA2 (BRCA1/2) mutations, despite effective interventions to reduce risk. We report disclosure and uptake patterns by BRCA1/2-positive individuals to at-risk relatives, in the setting of no-cost genetic counseling and testing. METHODS: Relatives of BRCA1/2-positive individuals were offered cost-free and confidential genetic counseling and testing. If positive for a BRCA1/2 mutation, participants were eligible to complete a survey about their disclosure of mutation status and the subsequent uptake of genetic testing by at-risk family members. RESULTS: One hundred and fifteen of 142 eligible individuals responded to the survey (81%). Eighty-eight (77%) of those surveyed disclosed results to all at-risk relatives. Disclosure to first-degree relatives (FDRs) was higher than to second-degree relatives (SDRs) and third-degree relatives (TDR) (95% vs. 78%; p < 0.01). Disclosure rates to male versus female relatives were similar, but reported completion of genetic testing was higher among female versus male FDRs (73% vs. 49%; p < 0.01) and SDRs (68% vs. 43%; p < 0.01), and among members of maternal versus paternal lineages (63% vs. 0%; p < 0.01). Men were more likely than women to express general difficulty discussing positive BCRA1/2 results with at-risk family members (90% vs. 70%; p = 0.03), while women reported more emotional distress associated with disclosure than men (48% vs. 13%; p < 0.01). DISCUSSION: We report a very high rate of disclosure of genetic testing information to at-risk relatives. However, uptake of genetic testing among at-risk individuals was low despite cost-free testing services, particularly in men, SDRs, and members of paternal lineages. The complete lack of testing among paternally related at-risk individuals and the lower testing uptake among men signify a significant barrier to testing and a challenge for genetic counselors and physicians working with high-risk groups. Further research is necessary to ensure that family members understand their risk and the potential benefits of genetic counseling.     

Proceed with Care: Direct Predictive Testing for Huntington Disease

The cloning of the Huntington disease (HD) gene allows highly accurate predictive testing using direct analysis of the CAG repeat. This new test provides results with almost complete certainty but poses unique counseling issues related to direct testing for an adult-onset disease. These include testing individuals who are at 25% risk, without the need for blood from a 50% at risk relative; the assessment of symptomatic individuals; the need for ongoing counseling despite simplification of laboratory procedures; and counseling of persons from families who represent a new mutation for HD. This paper describes protocols for direct predictive testing for adult and prenatal assessment, on the basis of the experience of the Canadian Collaborative Study on Predictive Testing (CCSPT). Over the past 8 years, we have provided >400 results by using linked markers and, more recently, 416 results by using direct assessment of CAG expansion in the HD gene. The vast majority (86%) of requests for direct predictive testing have been from persons who have not previously received results by using linked markers. Despite the ability to now directly assess for the mutation associated with HD, we still recommend assessment of DNA from an affected relative, as this may significantly enhance the accuracy of information to be provided to the at-risk individual. Distance from a genetics center has previously limited the availability of testing, and therefore we have developed approaches to providing predictive testing in the patient's own community.     

Susceptibility genes and the question of embodied identity

Drawing on an assumption of the co-construction of the material and the social, late-onset Alzheimer's disease (AD) is used as an illustrative example to assess claims for an emergent figure of the "individual genetically at risk." Current medical understanding of the genetics of AD is discussed, followed by a summary of media and AD society materials that reveal an absence of gene hype in connection with this disease. Excerpts from interviews with first-degree relatives of patients diagnosed with AD follow. Interviewees hold complex theories of causation. After genetic testing they exhibit few if any subjective changes in embodied identity or lifestyle. Family history is regarded by interviewees as a better indicator of future disease than is genetic testing. We argue that, even when molecular genetics are better understood, predictions about complex disease based on genotyping will be fraught with uncertainty, making problematic the concept of individuals as genetically at risk when applied to late-onset complex disease.     

Presymptomatic detection or exclusion of prion protein gene defects in families with inherited prion diseases.

The identification of defects in the prion protein (PrP) gene in families with inherited Creutzfeldt-Jakob disease or Gerstmann-Straussler syndrome allows presymptomatic diagnosis or exclusion of these disorders in subjects at risk. After counseling, PrP gene analysis was performed in three such individuals: two from families with a 144-bp insert and one with a point mutation at codon 102 in the PrP gene. The presence of a PrP gene defect was confirmed in one and excluded in two. Despite the potential problems of using PrP gene analysis in genetic prediction - specifically, uncertainty about penetrance and, generally, problems of presymptomatic testing in any inherited late-onset neurodegenerative disorder - we conclude that it has a role to play in improved genetic counseling for families with inherited prion diseases.     

Genome-Wide Diet-Gene Interaction Analyses for Risk of Colorectal Cancer

Dietary factors, including meat, fruits, vegetables and fiber, are associated with colorectal cancer; however, there is limited information as to whether these dietary factors interact with genetic variants to modify risk of colorectal cancer. We tested interactions between these dietary factors and approximately 2.7 million genetic variants for colorectal cancer risk among 9,287 cases and 9,117 controls from ten studies. We used logistic regression to investigate multiplicative gene-diet interactions, as well as our recently developed Cocktail method that involves a screening step based on marginal associations and gene-diet correlations and a testing step for multiplicative interactions, while correcting for multiple testing using weighted hypothesis testing. Per quartile increment in the intake of red and processed meat were associated with statistically significant increased risks of colorectal cancer and vegetable, fruit and fiber intake with lower risks. From the case-control analysis, we detected a significant interaction between rs4143094 (10p14/near GATA3) and processed meat consumption (OR = 1.17; p = 8.7E-09), which was consistently observed across studies (p heterogeneity = 0.78). The risk of colorectal cancer associated with processed meat was increased among individuals with the rs4143094-TG and -TT genotypes (OR = 1.20 and OR = 1.39, respectively) and null among those with the GG genotype (OR = 1.03). Our results identify a novel gene-diet interaction with processed meat for colorectal cancer, highlighting that diet may modify the effect of genetic variants on disease risk, which may have important implications for prevention.     

The use of association data to identify family members at high risk for marker-linked diseases.

The study of genetic markers linked and associated with disease has provided important evidence of a genetic contribution to numerous diseases and has helped to establish their modes of inheritance. However, this information has not been fully utilized in counseling individuals at risk for these disorders. In the case of recessive, marker-linked diseases, such as idiopathic hemochromatosis linked to HLA in family studies and associated with specific HLA alleles in population surveys, the only current clinical application has been to identify siblings who share both HLA-marker haplotypes with the affected proband. They are considered to be presymptomatically affected, and more definitive invasive investigations are considered appropriate. All other relatives, including parents, offspring, and other siblings, who share only one marker with the proband, have been counseled only that their risk is equivalent to the gene frequency of the disease allele, for example, 3%-6% for hemochromatosis. We have developed a generally applicable method to utilize population association data to derive more specific and accurate risk figures for these other relatives of patients with marker-linked and associated diseases. We have applied this method to idiopathic hemochromatosis. If the offspring of a patient with hemochromatosis lacks A3, B7, and B14, the risk to that offspring for developing hemochromatosis is less than 2%. On the other hand, if they receive HLA A3 from their unaffected parent, their risk climbs to 9%-10%; if they receive an A3-B14 haplotype, their risk increases to virtually 100%. As demonstrated by our example, the application of association data to family members already at a basal increased risk for marker-linked disease can significantly refine the disease risk estimates given to those relatives. This information can be utilized to select individuals in whom invasive diagnostic testing or preventative intervention is indicated.     

Attitude toward genetic testing for cancer risk in Istanbul

To identify attitudes toward genetic testing, and the effects of this information on decisions regarding issues such as pregnancy, abortion, and prophylactic surgery, several subsets of the Turkish population were surveyed in hospital settings. Individuals (n = 179) chosen arbitrarily from four different subsets of a Turkish population were asked to participate in a confidential 23-question survey. Survey participants were familiar with the concept of cancer being a familial disease (85.5%), and 84.7% of them expressed interest in genetic testing to determine cancer risk, 83.9% would have their fetuses tested for such cancer risk, 65.1% would terminate their pregnancies, 92.2% would have their children tested if they were determined to have an increased cancer risk, 71.9% would agree to undergo prophylactic oophorectomy or orchiectomy and 67.6% would have mastectomy/prostatectomy should there be an increased cancer risk to these organs. It appears that at least the sampled segment of a Turkish population is willing to undergo genetic testing to determine if they are at increased risk for cancer. The feasibility and acceptance of genetic testing and the influence of education and genetic counseling in the Turkish people should further be evaluated with a larger stratified sample of the population.