Risk For Hereditary Disease Research Articles

Returning personalized, genetic health test results to individuals of African descent or ancestry in precision medicine research.

Today, many epidemiological studies and biobanks are offering to disclose individual genetic results to their participants, including the National Institutes of Health's All of Us Research Program. Returning hereditary disease risks and pharmacogenetic test results to study participants from racial/ethnic groups that are historically underrepresented in biomedical research poses specific challenges to those participants and the health system writ large. For example, individuals of African descent are underrepresented in research about drug-gene interactions and have a relatively higher proportion of variants of unknown significance, affecting their ability to take clinical action following return of results. In this brief report, we summarize studies published to date concerning the perspectives and/or attitudes of African Americans engaged in genetic research programs to anticipate factors in disclosure protocols that would minimize risks and maximize benefits. A thematic analysis of studies identified (n = 6) lends to themes centered on motivations to engage or disengage in the return of results and integrating research and care. Actionable strategies determined in reaction to these themes center on ensuring adequate system and health education support for participants and personalizing the process for participants engaging in return of results. Overall, we offer these themes and actionable strategies as early guidance to research programs, and provide recommendations to policy makers focused on fair and equitable return of genetic research results to underrepresented research participants.

Evaluation of the Fetal-Maternal Radiation Doses in CT-Pelvimetry and Estimation of the Fetal Radiation Risks in 03 Radiology Departments in Douala-Cameroon

Background: CT in pregnant patients requires careful consideration of the radiation dose and corresponding radiation risks from ionizing radiation to the unborn child. The determination of foetal dose in diagnostic radiology is of interest as a basis for risk estimates from medical exposure of the pregnant patient. Objective: To evaluate the foetal-maternal radiation doses delivered during the CT-Pelvimetry procedure and to estimate the risk to the unborn child to develop a cancer in childhood and hereditary disease. Materials and Methods: We investigate the foetal-maternal radiation doses during CT-scan Pelvimetry in Douala (Cameroon). Data of 194 helical acquisition CT-Pelvimetry were collected between May 2017 and May 2019. An average DLP for the examination was established and the average effective dose was evaluated. The fetal dose was calculated and the FetDose V5 program was used for risk estimations. Results: The average dose length product (DLP) was 56.17 mGy·cm (range: 51.69 - 59.21 mGy·cm). The average effective dose received by women pregnant was 0.78 mSv. The mean individual fetal dose was 1.5 mGy (range: 0.76 - 1.87 mGy). The risk of Childhood Cancer calculated was: range 1 in 16,000 to 1 in 10,000 and 1 in 260,000 to 1 in 106,000 to the risk of Hereditary Disease, respectively. Conclusion: This study shows that the foetal-maternal doses delivered during CT-Pelvimetry examinations are very low and the risks of childhood cancers and hereditary diseases are derisory, the technology should be further investigated to ensure its full potential for optimal diagnostic accuracy.

ShareDNA: a smartphone app to facilitate family communication of genetic results

BackgroundGenetic testing allows patients and clinicians to understand the risk of hereditary diseases. By testing early, individuals can make informed medical decisions about management which may minimize the risk of developing certain diseases. Importantly, genetic test results may also be applicable to patients’ biological relatives; thus, these results could also lead to minimizing their risk of disease. However, sharing genetic test results between patients and their relatives is scarce. The most frequently reported problems are that patients cannot clearly explain this information and relatives misinterpret the results. Smartphone apps in the healthcare field are a possible solution as they allow patients to accurately share sensitive information to others, while providing educational material to support understanding the information. However, these apps may not provide security to protect patients’ identifiable information. We developed ShareDNA, a smartphone app that (1) allows patients to securely share their genetic test results with others, (2) provides information on how to interpret these results, and (3) minimizes the amount of patient information needed to use the service.ResultsWe recruited thirteen participants to test the usability of our app and provide feedback. We found overall that participants were comfortable with using this app and could easily learn each app function when filling out our questionnaire. Additionally, based on vocalized impressions of the usefulness of the app, participants indicated that the user-interface could be more intuitive and that we needed to add more text within the app to explain why ShareDNA is a secure service.ConclusionsShareDNA is a free smartphone app that allows patients to share their genetic test results with others, including their biological relatives. Sharing these results along with educational material will enable relatives to share accurate information and discuss their possible risk for disease with their clinical providers. As a result, appropriate testing in relatives could be improved.

Molecular genetics of disorders of sex development in a highly consanguineous population

Consanguinity increases the risk of hereditary diseases including disorders of sex development (DSD). There are minimal data on DSD in the highly consanguineous population of Saudi Arabia. This study reports the molecular genetics of a series of patients with different types of DSD. MethodsWe enrolled 77 patients from 47 families with DSD. DNA was isolated from peripheral leucocytes. Genes of interest were amplified by polymerase chain reaction and subsequently sequenced. ResultsOverall, 77 patients from 47 families (44 of them are consanguineous) had a total of 29 mutations; 16 of them were described before and 13 were novel mutations. The most common condition was 5-α reductase (SRD5A2) deficiency (25 patients from 18 families) and the most common mutation was a splice site mutation in intron 1 (c.282-2A>G). The next most common condition was 11-β hydroxylase (CYP11B1) deficiency where 19 patients from 10 families had 8 mutations (7 of them are novel). Other mutations affected CYP17A1 with 2 novel and 2 known mutations in 7 patients; HSD3B2 with 2 known mutations in 11 patients of 4 families; StAR with 1 novel and 1 known mutations in 4 patients; NR0B1 with 1 novel mutation in 2 siblings; HSD17B3 with 1 known mutation in 3 siblings; LHCGR with 1 novel mutation in 2 siblings; and AR with 1 novel and 3 known mutations in 4 unrelated patients. ConclusionIn the highly consanguineous and homogeneous population of Saudi Arabia, SRD5A2 and CYP11B1 deficiencies are common causes of DSDs. Other DSDs occur less frequently but often with novel mutations.

Abstract P6-08-22: Racial and ethnic variation in multi-gene panel genetic test results among individuals referred for genetic counseling at a large urban comprehensive cancer center

Abstract Background There are racial and ethnic differences in the prevalence and types of pathogenic mutations and variants of uncertain significance (VUS) in BRCA1 and BRCA2. Since the landmark May 13, 2013 Supreme Court Ruling invalidating the patent for BRCA1 and BRCA2 genetic testing, numerous gene panels have been utilized to identify individuals at high risk for hereditary disease due to mutations in other cancer predisposing genes. To better understand the prevalence of recurring pathogenic mutations and/or uncover novel mutations in specific racial and ethnic groups, we evaluated the mutational profile of individuals who had genetic counseling and testing at a large urban NCI designated Comprehensive Cancer Center. Methods Data was extracted from the Karmanos Cancer Institute (KCI) Cancer Genetic Counseling Service data base from May 13, 2013 through December, 31, 2018. The cohort consisted of 3,544 unrelated individuals evaluated for high-risk of hereditary disease and 1,868 who had panel testing at 6 sites across Michigan including Detroit. We estimated the prevalence of pathogenic mutations and VUS from multigene panels by race and ethnicity. Odds Ratios (OR) and 95% confidence intervals (CI) were calculated to compare the rate of pathogenic mutations and VUS in race and ethnic groups with non-Hispanic whites (NHW) indicated as the reference group. Results There were 1,868 (52.7%) individuals who had panel testing which included 67.4% NHW, 24.1% African American (AA), 2.2% Arab, 1.9% Ashkenazi Jewish (AJ), 1.0% Hispanic (H), and 3.4% other. There were 174 individuals with pathogenic mutations and 312 with VUS. Compared to NHW, AA individuals were less likely to have pathogenic mutations on multi-panel testing (OR, 95% CI, 0.20, 0.10-0.37) and more likely to have VUS (OR, 95% CI, 1.41, 1.07-1.85). There were no differences in pathogenic mutations or VUS for other race or ethnic groups. Within a common 18 gene panel (excluding BRCA1 and BRCA2), the five most common genes with a pathogenic mutation were ATM (23), CHEK2 (21), PALB2 (13) and MSH6 (11). The three most common genes and number of pathogenic mutations identified by race and ethnicity were NHW (ATM -21, CHEK2-21&MSH6 -8), AA (MSH6-1, RAD51C-1&TP53-1), and Arab (PALB2-2, RAD50-1 and BARD1-1). For AJ individuals there were 2 pathogenic mutations identified in the MSH6 gene. There were no pathogenic mutations seen in Hispanics. Conclusions Understanding the prevalence of mutations in multi-gene panels in specific racial and ethnic groups can lead to better identification of individuals at risk for hereditary cancer who can benefit from enhanced surveillance and risk reducing management. Citation Format: Michael Steven Simon, Nadine Abdallah, Hadeel Assad, Malini Surapaneni, Rachel Reagle, Nancie Petrucelli, Kristen Purrington. Racial and ethnic variation in multi-gene panel genetic test results among individuals referred for genetic counseling at a large urban comprehensive cancer center [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-22.

Family storytelling about hereditary cancer: Framing shared understandings of risk.

Family communication about the family's health history (FHH) is an important step in alerting individuals to their hereditary disease risks and facilitating prevention. Individuals often communicate about the FHH of hereditary cancer as a story, which highlights the importance of analyzing family narratives of hereditary cancer to better understand their relation to psychological and physical well-being. This study investigates the content of family stories by examining how narrative tone and framing relate to coping, perceptions of risk, and medical decision-making. The current study recruited 42 family dyads with a prevalent FHH of hereditary cancer to participate in dyadic phone interviews to jointly tell their family narrative of hereditary cancer. Using an iterative analysis, findings examine how families create a shared understanding of FHH and hereditary risk. Narrative tone reflects participants' psychological well-being and contributed to the way families framed their experiences. Common frames to family narratives of hereditary cancer included empowerment, adversity, laissez faire, and discrepant. Each frame gave insight into how families were coping, their perceptions of risk, and how they make medical decisions to manage those risks. Developing a better understanding of how families communicate about their hereditary cancer risks can aid in designing clinical interventions to help families re-frame their stories to promote improved health outcomes.

The Genomic Health of Ancient Hominins

The genomes of ancient humans, Neandertals, and Denisovans contain many alleles that influence disease risks. Using genotypes at 3,180 disease-associated loci, we estimated the disease burden of 147 ancient genomes. After correcting for missing data, genetic risk scores (GRS) were generated for nine disease categories and the set of all combined diseases. We used these genetic risk scores to examine the efffects of diffferent types of subsistence, geography, and sample age on the number of risk alleles in each ancient genome. On a broad scale, hereditary disease risks are similar for ancient hominins and modern-day humans, and the GRS percentiles of ancient individuals span the full range of what is observed in present-day individuals. In addition, there is evidence that ancient pastoralists may have had healthier genomes than hunter-gatherers and agriculturalists. We also observed a temporal trend whereby genomes from the recent past are more likely to be healthier than genomes from the deep past. This calls into question the idea that modern lifestyles have caused genetic load to increase over time. Focusing on individual genomes, we found that the overall genomic health of the Altai Neandertal is worse than 97% of present-day humans and that Ötzi, the Tyrolean Iceman, had a genetic predisposition for gastrointestinal and cardiovascular diseases. As demonstrated by this work, ancient genomes affford us new opportunities to diagnose past human health, which has previously been limited by the quality and completeness of remains.

No Magic Bullet: Genetic Diagnostics and Predictive Testing

The enormous increase in knowledge about the genetic basis of human diseases, combined with the rapid development of genetic techniques, has led to the possible use of genetic tests in medical diagnostics to a degree previously unknown. In addition, predictive genetic diagnostics has the aim of identifying hereditary disease risks in healthy individuals in order to take precautionary measures. However, the assessment of genetic findings is still subject to numerous problems. In particular, in the case of disease prediction, only probability statements can be made since endogenous and exogenous factors influence the penetrance and expressivity of genetically determined diseases.

The Genomic Health of Ancient Hominins.

The genomes of ancient humans, Neandertals, and Denisovans contain many alleles that influence disease risks. Using genotypes at 3,180 disease-associated loci, we estimated the disease burden of 147 ancient genomes. After correcting for missing data, genetic risk scores (GRS) were generated for nine disease categories and the set of all combined diseases. We used these genetic risk scores to examine the effects of different types of subsistence, geography, and sample age on the number of risk alleles in each ancient genome. On a broad scale, hereditary disease risks are similar for ancient hominins and modern-day humans, and the GRS percentiles of ancient individuals span the full range of what is observed in present-day individuals. In addition, there is evidence that ancient pastoralists may have had healthier genomes than hunter-gatherers and agriculturalists. We also observed a temporal trend whereby genomes from the recent past are more likely to be healthier than genomes from the deep past. This calls into question the idea that modern lifestyles have caused genetic load to increase over time. Focusing on individual genomes, we found that the overall genomic health of the Altai Neandertal is worse than 97% of present-day humans and that Ötzi, the Tyrolean Iceman, had a genetic predisposition for gastrointestinal and cardiovascular diseases. As demonstrated by this work, ancient genomes afford us new opportunities to diagnose past human health, which has previously been limited by the quality and completeness of remains.

Biased Gene Conversion Skews Allele Frequencies in Human Populations, Increasing the Disease Burden of Recessive Alleles

Gene conversion results in the nonreciprocal transfer of genetic information between two recombining sequences, and there is evidence that this process is biased toward G and C alleles. However, the strength of GC-biased gene conversion (gBGC) in human populations and its effects on hereditary disease have yet to be assessed on a genomic scale. Using high-coverage whole-genome sequences of African hunter-gatherers, agricultural populations, and primate outgroups, we quantified the effects of GC-biased gene conversion on population genomic data sets. We find that genetic distances (FST and population branch statistics) are modified by gBGC. In addition, the site frequency spectrum is left-shifted when ancestral alleles are favored by gBGC and right-shifted when derived alleles are favored by gBGC. Allele frequency shifts due to gBGC mimic the effects of natural selection. As expected, these effects are strongest in high-recombination regions of the human genome. By comparing the relative rates of fixation of unbiased and biased sites, the strength of gene conversion was estimated to be on the order of Nb ≈ 0.05 to 0.09. We also find that derived alleles favored by gBGC are much more likely to be homozygous than derived alleles at unbiased SNPs (+42.2% to 62.8%). This results in a curse of the converted, whereby gBGC causes substantial increases in hereditary disease risks. Taken together, our findings reveal that GC-biased gene conversion has important population genetic and public health implications.

DNA testing in neurologic diseases.

DNA testing is available for a growing number of hereditary diseases in neurology and other specialties. In addition to guiding breeding decisions, DNA tests are important tools in the diagnosis of diseases, particularly in conditions for which clinical signs are relatively nonspecific. DNA testing also can provide valuable insight into the risk of hereditary disease when decisions about treating comorbidities are being made. Advances in technology and bioinformatics will make broad screening for potential disease‐causing mutations available soon. As DNA tests come into more common use, it is critical that clinicians understand the proper application and interpretation of these test results.

Real-Time Interaction between TVR and the TATA Box of the Human Triosephosphate Isomerase Gene Promoter in the Norm and Pathology

The TATA-binding protein (TBP) is a key part of the transcription complex of RNA polymerase II. Alone or as a part of the basal transcription factor TFIID, TBP binds the TATA box located in the core region of the TATA-containing promoters of class II genes. Previously, we studied the effects of single nucleotide polymorphisms (SNPs) on TBP/TATA-box interactions using gel retardation assay. It was demonstrated that most SNPs in the TATA boxes of some human gene promoters cause a 2- to 4-fold decrease in TBP/TATA affinity, which is associated with an increased risk of hereditary diseases, such as β thalassemias of diverse severity, hemophilia B Leyden, myocardial infarction, thrombophlebitis, lung cancer, etc. In this work, the process of TBP/TATA complex formation has been studied in real time by a stopped-flow technique using recombinant human TBP and duplexes, which were identical to the TATA box of the wild-type and a SNP-containing triosephosphate isomerase gene promoter and were fluorescently labeled by the Cy3/Cy5 FRET pair. It has been demonstrated for the first time that real-time binding of TBP to the TATA box of the TPI gene promoter is complete within 10 s and is described by a single-stage kinetic model. The complex formation of TBP with the wild-type TATA box occurs 5.5 times faster and the complex dissociation occurs 31 times slower compared with the SNPcontaining TATA box. Within the first seconds of the interaction, TBP binds to and simultaneously bends the TATA box. Importantly, the TATA box of the wild-type TPI gene promoter requires lower TBP concentrations compared to the TATA box containing the -24T → G SNP, which is associated with neurological and muscular disorders, cardiomyopathy, and other diseases.

Fluoroscopic Radiation Exposure During Hip Arthroscopy

The purpose of this study was to assess the maximal dose area product (DAP) of radiation received by women during hip arthroscopy; we used computer modeling to determine the theoretical risk to a fetus. We studied 116 female patients of childbearing age who underwent hip arthroscopy. We retrospectively collected data from the procedure, hip pathologic process, and dose of irradiation in milligray. We calculated the theoretical dose of radiation to the fetus and the risk of childhood hereditary disease and cancer. Labral tear (52%) was the most common indication for hip arthroscopy, with labral resection the most common procedure undertaken. The maximal DAP to the patient was 9.52 mGy, and the maximal DAP was estimated to be 2.99 mGy to the fetus. The risk of hereditary disease and childhood cancer for the fetus was calculated to be 1 in 14,000 and 1 in 11,000, respectively. Fluoroscopy used in hip arthroscopy generates a maximal theoretical dose of 2.99 mGy to the fetus, which places the procedure in the low-risk category. Level IV, therapeutic case series.

Long-Term Reactions to Genetic Testing forBRCA1andBRCA2Mutations: Does Time Heal Women's Concerns?

Short-term reactions to BRCA1 and BRCA2 (BRCA1/2) genetic test results have been described in several reports, but the long-terms effects of testing have not been examined extensively. We conducted an observational study to characterize the long-term impact of genetic testing for BRCA1/2 mutations in 167 women who had received genetic test results at least 4 years ago. We also evaluated the relationship between genetic testing-specific reactions and breast and ovarian cancer screening to determine the behavioral significance of adverse reactions. Seventy-four percent of women were not experiencing any distress regarding their test result, 41% were not experiencing any uncertainty, and 51% had a score for positive experiences that was suggestive of low levels of adverse reactions in terms of family support and communication. Mutation carriers (odds ratio, 3.96; 95% CI, 1.44 to 10.89; P = .01) were most likely to experience distress. Only less time since disclosure was related significantly to experiencing uncertainty (odds ratio, 0.62; 95% CI, 0.44 to 0.88; P = .008). In terms of cancer screening, 81% of women had a mammogram during the year before study enrollment, 25% had magnetic resonance imaging (MRI), 20% had a transvaginal ultrasound, and 20% had a CA-125. Experiencing distress was associated significantly with having a CA-125 (χ(2) = 3.89, P = .05), and uncertainty was associated with having an MRI (χ(2) = 8.90, P = .003). Our findings show that women are not likely to experience genetic testing concerns several years after receiving BRCA1/2 test results; distress and uncertainty are not likely to have adverse effects on screening among women at risk for hereditary disease.

Successful application of the strategy of blastocyst biopsy, vitrification, whole genome amplification, and thawed embryo transfer for preimplantation genetic diagnosis of neurofibromatosis type 1

Objective Preimplantation genetic diagnosis (PGD) offers an alternative for women to carry an unaffected fetus risk of hereditary diseases. Trophectoderm biopsy may provide more cells for accurate diagnosis. However, the time allowed for transportation of the specimens to the laboratory and performance of molecular diagnosis is limited. We designed a PGD program of trophectoderm biopsy, vitrification of blastocysts, whole genome amplification (WGA), double confirmatory genotypings, and thawed embryo transfer. Case Report We conducted this strategy for a woman of familial neurofibromatosis type I (NF-1). She had a genotype of heterozygous c.6709C>T mutation of NF1 gene. Trophectoderm biopsies were performed on 13 blastocysts. Then, individual blastocyst was vitrified. WGA was performed for the samples, followed by genotypings with both real-time polymerase chain reaction and sequencing. Eight embryos were diagnosed as unaffected, four were affected, and one was inconclusive because of allele drop-out. In the next cycle, two unaffected blastocysts were thawed and transferred, that resulted in a singleton pregnancy. The pregnancy was confirmed as unaffected by means of chorionic villi sampling. Conclusion We first demonstrate successful application of blastocyst biopsy, vitrification, WGA, and thawed embryo transfer for PGD of a monogenic disease. Vitrification of blastocysts after biopsy permits sufficient time for shipment of samples and operation of molecular diagnosis.

Effect of Genetic Counseling and Testing for BRCA1 and BRCA2 Mutations in African American Women: A Randomized Trial

Background: Limited empirical data are available on the effects of genetic counseling and testing among African American women. Objective: To evaluate the effects of genetic counseling and testing in African American women based on different levels of exposure: (a) women who were randomized to culturally tailored (CTGC) and standard genetic counseling (SGC) to women who declined randomization (non-randomized group), (b) participants and non-participants in genetic counseling, and (c) BRCA1 and BRCA2 (BRCA1/2) test result acceptors and decliners. Design: Randomized trial of genetic counseling conducted from February 2003 to November 2006. Measures: We evaluated changes in perceived risk of developing breast cancer and cancer worry. Results: Women randomized to CTGC and SGC did not differ in terms of changes in risk perception and cancer worry compared to decliners. However, counseling participants had a significantly greater likelihood of reporting reductions in perceived risk compared to non-participants (p = 0.03). Test result acceptors also had a significantly greater likelihood of reporting decreases in cancer worry (p = 0.03). However, having a cancer history (p = 0.03) and a BRCA1/2 prior probability (p = 0.04) were associated with increases in cancer worry. Conclusions: Although CTGC did not lead to significant improvements in perceived risk or psychological functioning, African American women may benefit from genetic counseling and testing. Continued efforts should be made to increase access to genetic counseling and testing among African American women at increased risk for hereditary disease. But, follow-up support may be needed for women who have a personal history of cancer and those with a greater prior probability of having a BRCA1/2 mutation.

Molecular Genetics of Parathyroid Disease

Primary hyperparathyroidism (HPT) is often caused by a benign parathyroid tumor, adenoma; less commonly by multiglandular parathyroid disease/hyperplasia; and rarely by parathyroid carcinoma. Patients with multiple tumors require wider exploration to avoid recurrence and have increased risk for hereditary disease. Secondary HPT is a common complication of renal failure. Improved knowledge of the molecular background of parathyroid tumor development may help select patients for appropriate surgical treatment and can eventually provide new means of treatment. The present contribution summarizes more recent knowledge of parathyroid molecular genetics. A literature search and review was made to evaluate the level of evidence concerning molecular biology and genetics of primary, secondary, and familial HPT according to criteria proposed by Sackett, with recommendation grading by Heinrich et al. Most parathyroid adenomas and hyperplastic glands are monoclonal lesions. Cyclin D1 gene (CCND1) translocation and oncogene action occur in 8% of adenomas; cyclin D1 overexpression is seen in 20% to 40% of parathyroid adenomas and in 31% of secondary hyperplastic glands. Somatic loss of one MEN1 allele is seen in 25% to 40% of sporadic parathyroid adenomas, half of which have inactivating mutation of the remaining allele. Inactivating somatic HRPT2 mutations are common in parathyroid carcinoma, often causing decreased expression of the protein parafibromin involved in cyclin D1 regulation. Aberrant regulation of Wnt/beta-catenin signaling may be important for parathyroid tumor development. Molecular genetic studies of parathyroid tumors are well designed basic experimental studies providing strong level III evidence, with data frequently confirmed by subsequent studies.

Genetic counseling for BRCA1 and BRCA2 mutations in African American women.

Abstract Abstract #1099 Background: Efforts are now focused on increasing access to genetic counseling and testing for BRCA1 and BRCA2 (BRCA1/2) mutations to address cancer disparities in African American women; however, limited empirical data are available on the effects of these services. Therefore, we evaluated the effects of genetic counseling among African American women at increased risk for hereditary disease.
 Materials and Methods: This study was conducted between February 2003 and November 2006. Participants were African American women (n=139) at increased risk for having a BRCA1 or BRCA2 (BRCA1/2) mutation. The effects of genetic counseling, including culturally tailored (CTGC) versus standard (SGC) counseling, on changes in risk perception and psychological functioning were evaluated.
 Results: Women who participated in genetic counseling had a significantly greater likelihood of reporting reductions in perceived risk compared to non-participants (P=0.03). Women who received BRCA1/2 results also had a significantly greater likelihood of reporting decreases in cancer worry (P=0.03). Similar effects were found among women who had a high prior probability of having a BRCA1/2 mutation (P=0.03) and those affected with cancer (P=0.04). There were no differences in CTGC and SGC in study outcomes.
 Discussion: African American women may experience some benefit from receiving BRCA1/2 test results. Participation in counseling and receiving test results may be especially beneficial to African American women who have high prior probability of having a BRCA1/2 mutation and those affected with cancer. Continued efforts should be made to increase access to genetic counseling and testing among African American women at increased risk for hereditary disease. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1099.

Distinction between hereditary and sporadic breast cancer on the basis of clinicopathological data

Background: About 5% of all breast cancer cases are attributable to germline mutations in BRCA1 or BRCA2 genes. BRCA mutations in suspected carriers, however, may be missed, which hampers genetic...

The “duty to warn” a patient’s family members about hereditary disease risks

GENETIC TESTS FOR SPECIFIC ADULT-ONSET DISORders (eg, breast and colon cancer) are now commercially available, and results of research studies for genetic polymorphisms that predict drug effects, for example, response to statin therapy, have recently been published. The failure to warn family members about their hereditary disease risks has resulted in 3 malpractice suits against physicians in the United States. This past year, the obligation, if any, to warn family members of identification of a cancer gene mutation was the topic of discussion among professional societies and advocacy groups. Concerns have been raised regarding the conflict between the physician’s ethical obligations to respect the privacy of genetic information vs the potential legal liabilities resulting from the physician’s failure to notify at-risk relatives. In many cases, state and federal statutes that bear on the issue of “duty to warn” of inherited health risk are also in conflict. This article discusses these issues and suggests that health care professionals have a responsibility to encourage but not to coerce the sharing of genetic information in families, while respecting the boundaries imposed by the law and by the ethical practice of medicine.