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At least 19 recordsLinked to original sources
PubMed2000

Perception of genetic risk among genetic counselors.

A mailed survey of female prenatal genetic counselors, obstetric nurses, and high school biology teachers was conducted to determine if these groups hold different attitudes toward genetic risk and to investigate the extent to which any differences result from the effect of different professional experiences. In this study, the participants were 166 genetic counselors, 116 obstetric nurses, and 78 biology teachers (n=360). Survey participants completed a written questionnaire designed to assess their numeric estimate of the empiric risk for birth defects/genetic problems, their subjective perception of this risk, and their personal use of prenatal diagnosis. Genetic counselors were found to be less likely than the other groups to consider the frequency of birth defects/genetic problems as rare and were 10 times more likely than nurses and 8 times more likely than teachers to have had prenatal diagnosis. Furthermore, more than half of the prenatal diagnosis procedures had by genetic counselors were not medically indicated. These results suggest that genetic counselors have an increased perception of genetic risks relative to nurses or teachers. Possible explanations for this funding are discussed, and the potential role of discordant risk perception in creating biases in genetic counseling process is explored.

Attitude↗
PubMed1994

Meeting report of the EC/US workshop on genetic risk assessment: "human genetic risks from exposure to chemicals, focusing on the feasibility of a parallelogram approach".

This workshop was the concept of Professor Frits Sobels who passed away on the 6th of July 1993. The underlying idea of the Sobels' parallelogram approach is that an estimate (corrected by DNA-adduct dosimetry) of the genetic damage in human germ cells can be obtained by measuring a common endpoint in human and mouse somatic cells (such as gene mutation in lymphocytes) and in germ cells of mice, the desired target tissue inaccessible in humans. The main objective of the workshop was to identify the methodology, data requirements and mechanistic research to understand the human health impact of germ-cell mutagens. 4 chemicals were selected for review at the meeting: ethylene oxide, 1,3-butadiene, acrylamide and cyclophosphamide. The first 3 are important industrial chemicals with substantial use worldwide and, therefore, considerable potential human exposure. The 4th, cyclophosphamide, is a commonly used cancer chemotherapeutic agent. This first EC/US workshop on risk assessment was highly focused on the feasibility of the parallelogram concept to estimate potential germ-cell effects in humans. It represented an evaluation of current knowledge and the identification of future research needs for a more precise assessment of human genetic risks from exposure to mutagenic chemicals.

Animals↗
PubMed1980

[Use of the D7 strain of S. cerevisiae in the determination of environmental genetic risk. 2. Genetic effects of procarbazine].

Procarbazine was tested in vitro without and with S-10 fraction from mice liver (microsomal assay) using Saccharomyces cerevisiae strain D7, Salmonella typhimurium (strains TA 98, TA 100, TA 1535) and in vivo in Swiss albino mice (host mediated assay) using D7. Procarbazine without S-10 fraction was highly toxic and induced mitotic cross-over, gene conversion, and reverse mutation in D7. It had a toxic effect on all the Salmonella strains, but it did not induce any reverse mutations of the histidine mutants. In host-mediated assay using Saccharomyces, there was no genetic effect found in the indicator organism.

Animals↗
PubMed2000

Ionizing radiation and genetic risks. XIII. Summary and synthesis of papers VI to XII and estimates of genetic risks in the year 2000.

This paper recapitulates the advances in the field of genetic risk estimation that have occurred during the past decade and using them as a basis, presents revised estimates of genetic risks of exposure to radiation. The advances include: (i) an upward revision of the estimates of incidence for Mendelian diseases (2.4% now versus 1.25% in 1993); (ii) the introduction of a conceptual change for calculating doubling doses; (iii) the elaboration of methods to estimate the mutation component (i.e. the relative increase in disease frequency per unit relative increase in mutation rate) and the use of the estimates obtained through these methods for assessing the impact of induced mutations on the incidence of Mendelian and chronic multifactorial diseases; (iv) the introduction of an additional factor called the "potential recoverability correction factor" in the risk equation to bridge the gap between radiation-induced mutations that have been recovered in mice and the risk of radiation-inducible genetic disease in human live births and (v) the introduction of the concept that the adverse effects of radiation-induced genetic damage are likely to be manifest predominantly as multi-system developmental abnormalities in the progeny. For all classes of genetic disease (except congenital abnormalities), the estimates of risk have been obtained using a doubling dose of 1 Gy. For a population exposed to low LET, chronic/ low dose irradiation, the current estimates for the first generation progeny are the following (all estimates per million live born progeny per Gy of parental irradiation): autosomal dominant and X-linked diseases, approximately 750-1500 cases; autosomal recessive, nearly zero and chronic multifactorial diseases, approximately 250-1200 cases. For congenital abnormalities, the estimate is approximately 2000 cases and is based on mouse data on developmental abnormalities. The total risk per Gy is of the order of approximately 3000-4700 cases which represent approximately 0.4-0.6% of the baseline frequency of these diseases (738,000 per million) in the population.

Animals↗
PubMed2001

Genetic risk: the new frontier for the duty to warn.

Mental health professionals usually think of the "duty to warn" in the context of mental illness. However, two state appellate courts have endorsed a duty to warn when children of a patient may be at risk genetically for acquiring the disease of their parents. In these cases, the courts held that a physician's legal obligations extended beyond his or her patient to the patient's children. This article discusses these cases, as well as issues regarding implementation of such a duty and the implications for the physician-patient relationship in a health care environment that will be dominated increasingly by genetics issues. The article concludes that it is premature to apply a duty to warn to the treatment of mental illness and to concerns regarding future criminal behavior.

Crime↗
PubMed2003

To tell or not to tell: barriers and facilitators in family communication about genetic risk.

Communication about genetic risk in families is an important issue for genetic counsellors. The objective of this study was to explore the barriers and facilitators in family communication about genetic risk. Semi-structured interviews were undertaken with patients in the Northeast of Scotland who had attended genetic counselling for risk of hereditary breast and ovarian cancer and Huntington's disease, and with some spouses/partners. The interviews confirmed that the issue of disclosure was a problem for some, and that there were generic communication issues common to both groups. Telling family members about genetic risk was generally seen as a family responsibility and family structures, dynamics and 'rules' influenced disclosure decisions. A sense of responsibility towards younger generations was also important. The level of certainty felt by a person in relation to his or her own risk estimate also influenced what he or she could tell other family members. Communication within a family about genetic risk is a complex issue and is influenced by both pre-existing familial and cultural factors and individuals' responses to risk information. If genetic counsellors understood how these factors operate in individual families they might be able to identify effective strategies to promote considered decisions and prevent unnecessary emotional distress.

Adult↗
PubMed2001

Assessing genetic risk: comparison between the referring obstetrician and genetic counselor.

OBJECTIVE: To compare the genetic risk assessment of the referring obstetrician to the risk assessment of the genetic counselor. STUDY DESIGN: All patients evaluated between January 1, 1999, and March 31, 1999, and who required genetic counseling were retrospectively reviewed. The genetic risk assessment of the referring obstetrician was compared to the genetic risk assessment following counseling by a genetic counselor who used a questionnaire and a three-generation pedigree. The number of patients with additional genetic risk factors identified by the genetic counselor were recorded and compared by using the McNemar chi-square test. Group demographics and characteristics were evaluated. RESULTS: Among the 145 patients evaluated, 38% (n = 55) had additional genetic risk factors detected by the genetic counselor (P =.01). The maternal demographics and characteristics did not differ between the two groups. CONCLUSION: The practice of referring high-risk obstetric patients for genetic counseling improves the detection of identifiable genetic risk factors.

Genetic Counseling↗
PubMed2000

Ionizing radiation and genetic risks. XII. The concept of "potential recoverability correction factor" (PRCF) and its use for predicting the risk of radiation-inducible genetic disease in human live births.

Genetic risks of radiation exposure of humans are generally expressed as expected increases in the frequencies of genetic diseases over those that occur naturally in the population as a result of spontaneous mutations. Since human data on radiation-induced germ cell mutations and genetic diseases remain scanty, the rates derived from the induced frequencies of mutations in mouse genes are used for this purpose. Such an extrapolation from mouse data to the risk of genetic diseases will be valid only if the average rates of inducible mutations in human genes of interest and the average rates of induced mutations in mice are similar. Advances in knowledge of human genetic diseases and in molecular studies of radiation-induced mutations in experimental systems now question the validity of the above extrapolation. In fact, they (i) support the view that only in a limited number of genes in the human genome, induced mutations may be compatible with viability and hence recoverable in live births and (ii) suggest that the average rate of induced mutations in human genes of interest from the disease point of view will be lower than that assumed from mouse results. Since, at present, there is no alternative to the use of mouse data on induced mutation rates, there is a need to bridge the gap between these and the risk of potentially inducible genetic diseases in human live births. In this paper, we advance the concept of what we refer to here as "the potential recoverability correction factor" (PRCF) to bridge the above gap in risk estimation and present a method to estimate PRCF. In developing the concept of PRCF, we first used the available information on radiation-induced mutations recovered in experimental studies to define some criteria for assessing potential recoverability of induced mutations and then applied these to human genes on a gene-by-gene basis. The analysis permitted us to estimate unweighted PRCFs (i.e. the fraction of genes among the total studied that might contribute to recoverable induced mutations) and weighted PRCFs (i.e. PRCFs weighted by the incidences of the respective diseases). The estimates are: 0.15 (weighted) to 0.30 (unweighted) for autosomal dominant and X-linked diseases and 0.02 (weighted) to 0.09 (unweighted) for chronic multifactorial diseases. The PRCF calculations are unnecessary for autosomal recessive diseases since the risks projected for the first few generations even without using PRCFs are already very small. For congenital abnormalities, PRCFs cannot be reliably estimated. With the incorporation of PRCF into the equation used for predicting risk, the risk per unit dose becomes the product of four quantities (risk per unit dose=Px(1/DD)xMCxPRCF) where P is the baseline frequency of the genetic disease, 1/DD is the relative mutation risk per unit dose, MC is the mutation component and PRCF is the disease-class-specific potential recoverability correction factor instead of the first three (as has been the case thus far). Since PRCF is a fraction, it is obvious that the estimate of risk obtained with the revised risk equation will be smaller than previously calculated values.

Genetic Diseases, Inborn↗
PubMed2024

Cardiovascular Risk Factors and Genetic Risk in Transthyretin V142I Carriers.

BACKGROUND: Nearly 3% to 4% of Black individuals in the United States carry the transthyretin V142I variant, which increases their risk of heart failure. However, the role of cardiovascular (CV) risk factors (RFs) in influencing the risk of clinical outcomes among V142I variant carriers is unknown. OBJECTIVES: This study aimed to assess the impact of CV RFs on the risk of heart failure in V142I carriers. METHODS: This study included self-identified Black individuals without prevalent heart failure from 6 TOPMed (Trans-Omics for Precision Medicine) cohorts, the REGARDS (Reasons for Geographic And Racial Differences in Stroke) study, and the All of Us Research Program. The cohort was stratified based on the V142I genotype and the number of CV RFs (hypertension, diabetes, obesity, and hypercholesterolemia). Adjusted Cox models were used to assess the association of heart failure with the V142I genotype and CV RF profile, taking noncarriers with a favorable CV RF profile as reference. RESULTS: The cross-sectional analysis, including 1,625 V142I carriers among 48,365 Black individuals, found that the prevalence of CV RFs did not vary by V142I carrier status. In the longitudinal analysis, there were 587 (3.2%) V142I carriers among 18,407 Black individuals (median age: 60 years [Q1-Q3: 52-68 years], 63.0% female). Among carriers, the heart failure risk was attenuated with a favorable (0 or 1 RF) CV RF profile (adjusted HR: 2.26; 95% CI: 1.58-3.23) compared with an unfavorable (3 or 4 RFs) CV RF profile (adjusted HR: 4.14; 95% CI: 2.79-6.14). CONCLUSIONS: A favorable CV RF profile lowers but does not abrogate V142I variant-associated heart failure risk. This study highlights the importance of having a favorable CV RF profile among V142I carriers for risk reduction of heart failure.

Aged↗
PubMed1995

EC/US workshop report: assessment of genetic risks associated with exposure to ethylene oxide, acrylamide, 1,3-butadiene and cyclophosphamide.

The EC/US Workshop on Risk Assessment: 'Human Genetic Risks from Exposure to Chemicals, Focusing on the Feasibility of a Parallelogram Approach' had as its main objective the identification of the methodology, data requirements and mechanistic research to understand the human health impact of germ cell mutagens. Specifically, it represented an evaluation of current knowledge and the identification of future research needs for a more precise assessment of human genetic risks from exposure to mutagenic chemicals. Four chemicals were selected for review at the Workshop and in this Special Issue: ethylene oxide, 1,3-butadiene, acrylamide, and cyclophosphamide. The first three are important industrial chemicals with substantial use worldwide and, therefore, considerable potential for human exposure. The fourth, cyclophosphamide, is a commonly used cancer chemotherapeutic agent. This Special Issue contains the major scientific reports from the workshop. These include four Introductory Papers (on the parallelogram concept, alternative genetic risk assessment approaches, regulatory data needs, and the research background for risk assessment of ethylene oxide), four Working Group Reports on the specific compounds mentioned above and, finally, three Crosscutting Papers pertinent to the issue of germ-line mutagenesis and genetic risk estimation.

Acrylamide↗
PubMed2004

Biology of epithelial ovarian cancer: implications for screening women at high genetic risk.

PURPOSE: Our aim was to analyze the clinicopathologic features of screen-detected ovarian cancers identified in women, either at general population risk or high genetic risk of ovarian cancer, who have participated in screening studies. METHODS: Studies published between 1988 and April 2003 were categorized by the population screened and the primary screening modalities used. Each report was examined with reference to the histologic type, stage, and grade of screen-detected cancers. Reports of studies of prophylactically removed ovaries from women at high risk of ovarian cancer were also reviewed. RESULTS: Of the stage I tumors detected by screening women at population risk, almost half were borderline ovarian tumors, granulosa-cell tumors, or germ-cell tumors, which is disproportionate to their frequency. Furthermore, of the stage I invasive epithelial cancers diagnosed in women at population risk, the majority were endometrioid, clear-cell, and mucinous histologic subtypes. Most ovarian cancers that occur in women at high genetic risk are high-grade serous cancers, and these are infrequently screen detected at an early stage. CONCLUSION: The clinicopathologic features of screen-detected ovarian cancers suggest that screening may not reduce mortality in women at increased genetic risk. Prospective screening studies are required in genetically high-risk populations to answer this important question. Women electing surveillance should be aware of the lack of proven benefit and the low likelihood of detecting early stage serous cancers. Bilateral salpingo-oophorectomy appears to be the most effective approach to decrease the risk of ovarian cancer and thereby reduce mortality in high-risk women.

Adenocarcinoma, Clear Cell↗
PubMed2004

Familial clustering and genetic risk for dementia in a genetically isolated Dutch population.

Despite advances in elucidating the genetic epidemiology of Alzheimer's disease and frontotemporal dementia, the aetiology for most patients with dementia remains unclear. We examined the genetic epidemiology of dementia in a recent genetically isolated Dutch population founded around 1750. The series of 191 patients ascertained comprised 122 probable Alzheimer's disease patients with late onset and 17 with early onset, and 22 with possible Alzheimer's disease. It further included 10 patients with vascular dementia, nine with Lewy body dementia and six with frontotemporal dementia. All patients, except those with vascular dementia, were more closely related than healthy individuals from the same area. Clustering was strongest for patients with early-onset Alzheimer's disease or Lewy body dementia. Although 14% of late-onset Alzheimer's disease patients had evidence of autosomal dominant disease, consanguinity was found in three late-onset Alzheimer's disease patients, suggesting a recessive or polygenic model underlying the trait. We found no clustering of vascular dementia, implying a difference in genetic risk for late-onset Alzheimer's disease and vascular dementia. Mutations in known genes could not explain the occurrence of dementia, but the population attributable proportion of apolipoprotein E gene (APOE*4) was high (45%) due to a high frequency of APOE*4 carriers. Earlier identified regions on chromosomes 10 and 12, nor the effect of the alpha-2-macroglobulin (A2M) I/D polymorphism on Alzheimer's disease could be confirmed in our study. We did find evidence for association between the A2M D-allele and Lewy body dementia. Our data showed a strong familial clustering of various forms of dementia in this isolated Dutch population. A high percentage of late-onset Alzheimer's disease could be explained by APOE*4, but 55% of its origin is still unknown.

Age of Onset↗
PubMed1999

Knowledge of no return--getting and giving information about genetic risk.

New genetic information can provide constructive preventive possibilities for individuals and for society but can also create new dilemmas for them. In consultations dealing with the risk of inheriting cancer, many problems connected with the notion of information exchange come to the surface. Individuals have to deal not only with the information given by the doctor, or how to give information to the doctor, but also with the problem of informing others, close kin with a similar risk potential, or getting information from them. In all these information exchanges concerning risk of cancer, different notions of 'information' are being invoked and used as resources in the talks, implying communicative problems at different levels. Some of these problems are discussed in this article.

Genetic Counseling↗
PubMed2000

Primary biliary cirrhosis and autoimmunity: evaluating the genetic risk.

The genetic basis of autoimmunity is receiving increased attention. Organ-specific diseases, such as primary biliary cirrhosis, may be considered model diseases to use for development of databases and extrapolation to other autoimmune diseases. PBC is an enigmatic autoimmune disease that predominantly affects females and leads to destruction of intrahepatic bile ducts. The serologic hallmark of this disease is anti-mitochondrial antibodies that specifically react with the E2 components of 2-oxodehydrogenase enzymes, including PDC-E2. There are no clear major histocompatibility complex associations with the development of PBC, despite the observation that first-degree relatives of index patients with PBC have a 4-6% prevalence of development of PBC. This risk factor is comparable or higher than any other human autoimmune disease and suggests that a genome-wide approach towards dissection of genetic associations would lead to valuable new insights. In this review we place these concepts in perspective and highlight in particular the genetic associations in primary biliary cirrhosis.

Adult↗
PubMed2002

[Genetic risk factors of thrombosis].

Genetic risk factors became a frequent predisposing cause of venous thromboembolism (VTE) since the discovery of two mutations: factor V Leiden and G20210A mutation of prothrombin gene. One of these both mutations is associated with around 25% of VTE events. Interaction of genetic risk factors, such as interaction of FV Leiden or G20210A mutation of prothrombin with antithrombin, protein C or protein S deficiencies, as well as interaction with acquired risk factors, have demonstrated that venous thrombosis is a multifactorial disease. The search for thrombophilia must be done in VTE occurring before the age of 45, in case of recurrencies and in case of familial history of VTE.

Adult↗
PubMed1990

Trade-off between gestational age and miscarriage risk of prenatal testing: does it vary according to genetic risk?

It has been generally assumed that as genetic risk rises, so the higher procedure-related miscarriage rates of diagnostic tests done earlier in gestation become more acceptable. To test the hypothesis a decision tree was used, in which the only differences between two tests A and B were that A was carried out earlier in pregnancy and was more likely to cause miscarriage. Over a wide range of rankings for the three outcomes (procedure-related miscarriage of a normal baby, early termination of pregnancy after test A, late termination of pregnancy after test B), the expected utility (relative desirability) of an earlier, but more risky, test was greater at a high (1 in 4) than at a low (1 in 100) genetic risk.

Abortion, Spontaneous↗