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1.
Eur J Med Genet ; 63(12): 104080, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33039684

RESUMO

In case of suspected hereditary predisposition to digestive cancers, next-generation sequencing can analyze simultaneously several genes associated with an increased risk of developing these tumors. Thus, "Gastro Intestinal" (GI) gene panels are commonly used in French molecular genetic laboratories. Lack of international recommendations led to disparities in the composition of these panels and in the management of patients. To harmonize practices, the Genetics and Cancer Group (GGC)-Unicancer set up a working group who carried out a review of the literature for 31 genes of interest in this context and established a list of genes for which the estimated risks associated with pathogenic variant seemed sufficiently reliable and high for clinical use. Pancreatic cancer susceptibility genes have been excluded. This expertise defined a panel of 14 genes of confirmed clinical interest and relevant for genetic counseling: APC, BMPR1A, CDH1, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2, POLD1, POLE, PTEN, SMAD4 and STK11. The reasons for the exclusion of the others 23 genes have been discussed. The paucity of estimates of the associated tumor risks led to the exclusion of genes, in particular CTNNA1, MSH3 and NTHL1, despite their implication in the molecular pathways involved in the pathophysiology of GI cancers. A regular update of the literature is planned to up-grade this panel of genes in case of new data on candidate genes. Genetic and epidemiological studies and international collaborations are needed to better estimate the risks associated with the pathogenic variants of these genes either selected or not in the current panel.

2.
Eur J Med Genet ; 63(12): 104078, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33059073

RESUMO

MUTYH-associated polyposis (MAP) was first described in 2002. It is an autosomal recessive condition associated with germline pathogenic variants of both MUTYH alleles. In 2011, a group of French experts reviewed the available data on this syndrome and established recommendations concerning the indications and strategies for molecular analysis of the MUTYH gene in index cases and their relatives, as well as the clinical management of affected individuals under the auspices of the French Institut National du Cancer (INCa). Some of these recommendations have become obsolete as a result of recent progress, especially those concerning the molecular strategy for MUTYH testing, as this gene has recently been included in a consensus panel of 14 colorectal cancer predisposition genes, justifying revision of the previous report. We report here the revised version of this work, which successively considers the phenotype and tumor risks associated with this genotype, differential diagnoses, criteria and strategy for molecular genetic testing and recommendations for the management of affected individuals. We also discuss the phenotype and tumor risks associated with monoallelic pathogenic variants of MUTYH.

3.
Bull Cancer ; 107(5): 586-600, 2020 May.
Artigo em Francês | MEDLINE | ID: mdl-32362383

RESUMO

MUTYH-associated polyposis (MUTYH-associated polyposis, MAP) is an autosomal recessive inheritance disorder related to bi-allelic constitutional pathogenic variants of the MUTYH gene which was first described in 2002. In 2011, a group of French experts composed of clinicians and biologists, performed a summary of the available data on this condition and drew up recommendations concerning the indications and the modalities of molecular analysis of the MUTYH gene in index cases and their relatives, as well as the management of affected individuals. In view of recent developments, some recommendations have become obsolete, in particular with regard to the molecular analysis strategy since MUTYH gene has been recently included in a consensus panel of 14 genes predisposing to colorectal cancer. This led us to revise all the points of the previous expertise. We report here the revised version of this work which successively considers the phenotype and the tumor risks associated with this genotype, the differential diagnoses, the indication criteria and the strategy of the molecular analysis and the recommendations for the management of affected individuals. We also discuss the phenotype and the tumor risks associated with mono-allelic pathogenic variants of MUTYH gene.


Assuntos
Polipose Adenomatosa do Colo/genética , DNA Glicosilases/genética , Polipose Adenomatosa do Colo/diagnóstico , Polipose Adenomatosa do Colo/terapia , Alelos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , DNA Glicosilases/análise , Diagnóstico Diferencial , Neoplasias do Sistema Digestório/genética , Saúde da Família , França , Predisposição Genética para Doença , Humanos , Neoplasias/genética , Fenótipo
4.
Eur J Cancer ; 132: 100-103, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32335476

RESUMO

Direct-to-consumer (DTC) commercial companies offer genetic tests that are presented as allowing individuals the opportunity to increase their capacities to be in charge of their own healthcare managements. DTC companies deny performing medical tests, yet they provide data based on sequencing multigene panel or whole exome. This contradiction allows these companies to escape the requirements of a regulated medical practice that guarantees the quality of the tests, as well as the information and support for tested individuals. Herein, we illustrate the lack of such requirements by analysing the bad experience of a young man who dealt with DTC health genetic testing companies. There is an emergency for DTC testing to be either deprived of any medically relevant information, or carried out in a legally regulated medical framework.


Assuntos
Erros de Diagnóstico/prevenção & controle , Triagem e Testes Direto ao Consumidor/normas , Indústria Farmacêutica/normas , Testes Genéticos/normas , Disseminação de Informação/ética , Neoplasias/diagnóstico , Análise de Sequência de DNA/normas , Adulto , Triagem e Testes Direto ao Consumidor/legislação & jurisprudência , Indústria Farmacêutica/legislação & jurisprudência , Testes Genéticos/legislação & jurisprudência , Genoma Humano , Humanos , Achados Incidentais , Disseminação de Informação/legislação & jurisprudência , Masculino , Neoplasias/genética , Fatores de Risco
5.
Eur J Cancer Care (Engl) ; 29(1): e13173, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31571365

RESUMO

BACKGROUND: We performed a comprehensive assessment of the psychometrics of the "Psychosocial Aspects in Hereditary Cancer" (PAHC) questionnaire in French, German and Spanish. METHODS: Women consecutively approached in Cancer Genetic Clinics completed the PAHC, distress and satisfaction questionnaires at pre-testing (T1) and after test result disclosure (T2). In addition to standard psychometric attributes, we assessed the PAHC ability to respond to change (i.e. improvement or deterioration from T1 to T2) in perceived difficulties and computed minimal important differences (MID) in PAHC scores as compared with self-reported needs for additional counselling. RESULTS: Of 738 eligible counselees, 214 (90%) in France (Paris), 301 (92%) in Germany (Cologne) and 133 (77%) in Spain (Barcelona) completed the PAHC. A six-factor revised PAHC model yielded acceptable CFA goodness-of-fit indexes and good all scales internal consistencies. PAHC scales demonstrated expected conceptual differences with distress and satisfaction with counselling. Different levels of psychosocial difficulties were evidenced between counselees' subgroups and over time (p-values < .05). MID estimates ranged from 8 to 15 for improvement and 9 to 21 for deterioration. CONCLUSION: The PAHC French, German and Spanish versions are reliable and valid for evaluating the psychosocial difficulties of women at high BC risk attending genetic clinics.


Assuntos
Neoplasias da Mama/psicologia , Aconselhamento Genético/psicologia , Predisposição Genética para Doença/psicologia , Síndrome Hereditária de Câncer de Mama e Ovário/psicologia , Angústia Psicológica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Análise Fatorial , Feminino , França , Testes Genéticos , Alemanha , Humanos , Pessoa de Meia-Idade , Diferença Mínima Clinicamente Importante , Determinação de Necessidades de Cuidados de Saúde , Psicometria , Reprodutibilidade dos Testes , Espanha , Inquéritos e Questionários , Traduções , Adulto Jovem
6.
J Clin Oncol ; 38(7): 674-685, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31841383

RESUMO

PURPOSE: To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. METHODS: We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. RESULTS: We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10-76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10-3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10-3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 × 10-2). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 × 10-3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies (P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. CONCLUSION: These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.

7.
Psychooncology ; 29(3): 550-556, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31823434

RESUMO

BACKGROUND: Increasingly complex genetics counseling requires guidance to facilitate counselees' psychosocial adjustment. We explored networks of inter-relationships among coping strategies and specific psychosocial difficulties in women tested for hereditary breast or ovarian cancer. METHODS: Of 752 counselees consecutively approached, 646 (86%) completed questionnaires addressing coping strategies (Brief-COPE) and psychosocial difficulties (PAHC) after the initial genetic consultation (T1), and 460 (61%) of them again after the test result (T2). We applied network analysis comparing partial correlations among these questionnaire scales, according to the type of genetic test - single gene-targeted or multigene panel, test result and, before and after testing. RESULTS: Overall, 98 (21.3%), 259 (56.3%), 59 (12.8%) and 44 (9.6%) women received a pathogenic variant, uninformative negative (panel testing), variant of uncertain significance (VUS) or true negative (targeted testing) result, respectively. In most networks, connections were strongest between avoidance and general negative emotions. Cognitive restructuring was inter-related to lower psychosocial difficulties. Avoidance and familial/social relationship difficulties were strongly related in women receiving a pathogenic variant. Stronger inter-relationships were also noticed between avoidance and worries about personal cancer and concerns about hereditary predisposition in women receiving a VUS result. Differences in the prominence of inter-relationships were observed by type of testing and assessment time. CONCLUSIONS: Network analysis may be fruitful to highlight prominent inter-relationships among coping strategies and psychosocial difficulties, in women tested for HBOC susceptibility, offering guidance for counseling.


Assuntos
Neoplasias da Mama/psicologia , Aconselhamento Genético/psicologia , Predisposição Genética para Doença/psicologia , Síndromes Neoplásicas Hereditárias/psicologia , Neoplasias Ovarianas/psicologia , Adulto , Ansiedade/psicologia , Neoplasias da Mama/diagnóstico , Feminino , Testes Genéticos/estatística & dados numéricos , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Qualidade de Vida/psicologia , Inquéritos e Questionários , Saúde da Mulher/estatística & dados numéricos
9.
BMJ Open ; 9(9): e029926, 2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31551380

RESUMO

OBJECTIVES AND SETTING: Advances in multigene panel testing for cancer susceptibility has increased the complexity of counselling, requiring particular attention to counselees' psychosocial needs. Changes in psychosocial problems before and after genetic testing were prospectively compared between genetic test results in women tested for breast or ovarian cancer genetic susceptibility in French, German and Spanish clinics. PARTICIPANTS AND MEASURES: Among 752 counselees consecutively approached, 646 (86%) were assessed after the initial genetic consultation (T1), including 510 (68%) affected with breast cancer, of which 460 (61%) were assessed again after receiving the test result (T2), using questionnaires addressing genetic-specific psychosocial problems (Psychosocial Aspects of Hereditary Cancer (PAHC)-six scales). Sociodemographic and clinical data were also collected. RESULTS: Seventy-nine (17.2%), 19 (4.1%), 259 (56.3%), 44 (9.6%) and 59 (12.8%) women received a BRCA1/2, another high/moderate-risk pathogenic variant (PV), negative uninformative, true negative (TN) or variant of uncertain significance result (VUS), respectively. On multiple regression analyses, compared with women receiving another result, those with a VUS decreased more in psychosocial problems related to hereditary predisposition (eg, coping with the test result) (ß=-0.11, p<0.05) and familial/social issues (eg, risk communication) (ß=-0.13, p<0.05), almost independently from their problems before testing. Women with a PV presented no change in hereditary predisposition problems and, so as women with a TN result, a non-significant increase in familial/social issues. Other PAHC scales (ie, emotions, familial cancer, personal cancer and children-related issues) were not affected by genetic testing. CONCLUSIONS: In women tested for breast or ovarian cancer genetic risk in European genetics clinics, psychosocial problems were mostly unaffected by genetic testing. Apart from women receiving a VUS result, those with another test result presented unchanged needs in counselling in particular about hereditary predisposition and familial/social issues.


Assuntos
Adaptação Psicológica , Aconselhamento Genético , Predisposição Genética para Doença/psicologia , Testes Genéticos/métodos , Síndrome Hereditária de Câncer de Mama e Ovário , Comportamento Social , Adulto , Proteína BRCA1/genética , Feminino , França/epidemiologia , Aconselhamento Genético/métodos , Aconselhamento Genético/psicologia , Alemanha/epidemiologia , Síndrome Hereditária de Câncer de Mama e Ovário/epidemiologia , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Síndrome Hereditária de Câncer de Mama e Ovário/psicologia , Humanos , Psicologia , Espanha/epidemiologia , Estresse Psicológico/diagnóstico , Estresse Psicológico/etiologia
10.
J Med Ethics ; 45(12): 811-816, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31462451

RESUMO

Familial disclosure of genetic information is an important, long-standing ethical issue that still gives rise to much debate. In France, recent legislation has created an innovative and unprecedented procedure that allows healthcare professionals (HCPs), under certain conditions, to disclose relevant information to relatives of a person carrying a deleterious genetic mutation. This article will analyse how HCPs in two medical genetics clinics have reacted to these new legal provisions and show how their reticence to inform the patients' relatives on their behalf leads them to use this option sparingly.


Assuntos
Revelação/ética , Predisposição Genética para Doença , Testes Genéticos/ética , Confidencialidade/ética , Revelação/legislação & jurisprudência , Família , França , Predisposição Genética para Doença/psicologia , Testes Genéticos/legislação & jurisprudência , Humanos
12.
Breast ; 45: 29-35, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30822622

RESUMO

Multigene panel testing for breast and ovarian cancer predisposition diagnosis is a useful tool as it makes possible to sequence a considerable number of genes in a large number of individuals. More than 200 different multigene panels in which the two major BRCA1 and BRCA2 breast cancer predisposing genes are included are proposed by public or commercial laboratories. We review the clinical validity and clinical utility of the 26 genes most oftenly included in these panels. Because clinical validity and utility are not established for all genes and due to the heterogeneity of tumour risk levels, there is a substantial difficulty in the routine use of multigene panels if management guidelines and recommendations for testing relatives are not previously defined for each gene. Besides, the classification of variant of unknown significance (VUS) is a particular limitation and challenge. Efforts to classify VUSs and also to identify factors that modify cancer risks are now needed to produce personalised risk estimates. The complexity of information, the capacity to come back to patients when VUS are re-classified as pathogenic, and the expected large increase in the number of individuals to be tested especially when the aim of multigene panel testing is not only prevention but also treatment are challenging both for physicians and patients. Quality of tests, interpretation of results, information and accompaniment of patients must be at the heart of the guidelines of multigene panel testing.


Assuntos
Neoplasias da Mama/genética , Detecção Precoce de Câncer/normas , Predisposição Genética para Doença , Testes Genéticos/normas , Análise de Sequência/normas , Biomarcadores Tumorais/genética , Detecção Precoce de Câncer/métodos , Feminino , Genes BRCA1 , Genes BRCA2 , Testes Genéticos/métodos , Variação Genética , Humanos , Neoplasias Ovarianas/genética , Reprodutibilidade dos Testes , Análise de Sequência/métodos
14.
J Community Genet ; 10(1): 61-71, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29508368

RESUMO

The BOADICEA breast cancer (BC) risk assessment model and its associated Web Application v3 (BWA) tool are being extended to incorporate additional genetic and non-genetic BC risk factors. From an online survey through the BOADICEA website and UK, Dutch, French and Swedish national genetic societies, we explored the relationships between the usage frequencies of the BWA and six other common BC risk assessment tools and respondents' perceived importance of BC risk factors. Respondents (N = 443) varied in age, country and clinical seniority but comprised mainly genetics health professionals (82%) and BWA users (93%). Oncology professionals perceived reproductive, hormonal (exogenous) and lifestyle BC risk factors as more important in BC risk assessment compared to genetics professionals (p values < 0.05 to 0.0001). BWA was used more frequently by respondents who gave high weight to breast tumour pathology and low weight to personal BC history as BC risk factors. BWA use was positively related to the weight given to hormonal BC risk factors. The importance attributed to lifestyle and BMI BC risk factors was not associated with the use of BWA or any of the other tools. Next version of the BWA encompassing additional BC risk factors will facilitate more comprehensive BC risk assessment in genetics and oncology practice.

15.
Bull Cancer ; 105(10): 907-917, 2018 Oct.
Artigo em Francês | MEDLINE | ID: mdl-30268633

RESUMO

INTRODUCTION: Next generation sequencing allows the simultaneous analysis of large panel of genes for families or individuals with a strong suspicion of hereditary breast and/or ovarian cancer (HBOC). Because of lack of guidelines, several panels of genes potentially involved in HBOC were designed, with large disparities not only in their composition but also in medical care offered to mutation carriers. Then, homogenization in practices is needed. METHODS: The French Genetic and Cancer Group (GGC) - Unicancer conducted an exhaustive bibliographic work on 18 genes of interest. Only publications with unbiased risk estimates were retained. RESULTS: The expertise of each 18 genes was based on clinical utility criteria, i.e. a relative risk of cancer of 4 and more, available medical tools for screening and prevention of mutation carriers, and pre-symptomatic genetic tests for relatives. Finally, 13 genes were selected to be included in a HBOC diagnosis gene panel: BRCA1, BRCA2, PALB2, TP53, CDH1, PTEN, RAD51C, RAD51D, MLH1, MSH2, MSH6, PMS2, EPCAM. The reasons for excluding NBN, RAD51B, CHEK2, STK11, ATM, BARD1, BRIP1 from the HBOC diagnosis panel are presented. Screening, prevention and genetic counselling guidelines were detailed for each of the 18 genes. DISCUSSION: Due to the rapid increase in knowledge, the GGC has planned a yearly update of the bibliography to take into account new findings. Furthermore, genetic-epidemiological studies are being initiated to better estimate the cancer risk associated with genes which are not yet included in the HBOC diagnosis panel.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Neoplasias Ovarianas/genética , Antígenos CD , Caderinas , Proteínas de Ligação a DNA/genética , Molécula de Adesão da Célula Epitelial/genética , Proteína do Grupo de Complementação N da Anemia de Fanconi/genética , Feminino , França , Genes BRCA1 , Genes BRCA2 , Genes p53 , Marcadores Genéticos/genética , Humanos , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/genética , PTEN Fosfo-Hidrolase/genética
16.
Artigo em Inglês | MEDLINE | ID: mdl-29439543

RESUMO

With advances in breast cancer (BC) gene panel testing, risk counseling has become increasingly complex, potentially leading to unmet psychosocial needs. We assessed psychosocial needs and correlates in women initiating testing for high genetic BC risk in clinics in France and Germany, and compared these results with data from a literature review. Among the 442 counselees consecutively approached, 212 (83%) in France and 180 (97%) in Germany, mostly BC patients (81% and 92%, respectively), returned the 'Psychosocial Assessment in Hereditary Cancer' questionnaire. Based on the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) BC risk estimation model, the mean BC lifetime risk estimates were 19% and 18% in France and Germany, respectively. In both countries, the most prevalent needs clustered around the "living with cancer" and "children-related issues" domains. In multivariate analyses, a higher number of psychosocial needs were significantly associated with younger age (b = -0.05), higher anxiety (b = 0.78), and having children (b = 1.51), but not with country, educational level, marital status, depression, or loss of a family member due to hereditary cancer. These results are in line with the literature review data. However, this review identified only seven studies that quantitatively addressed psychosocial needs in the BC genetic counseling setting. Current data lack understandings of how cancer risk counseling affects psychosocial needs, and improves patient-centered care in that setting.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/psicologia , Aconselhamento Genético/psicologia , Assistência Centrada no Paciente/organização & administração , Adulto , Fatores Etários , Idoso , Ansiedade/etiologia , Neoplasias da Mama/complicações , Depressão/etiologia , Família/psicologia , Feminino , França , Predisposição Genética para Doença , Testes Genéticos/métodos , Alemanha , Humanos , Pessoa de Meia-Idade , Prevalência , Estresse Psicológico/etiologia , Inquéritos e Questionários , Adulto Jovem
17.
Fam Cancer ; 17(2): 281-285, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28819700

RESUMO

The invalidation of the Mismatch Repair (MMR) system is responsible for a so-called "deficient MMR" phenotype (dMMR) characterized by microsatellite instability and abnormal pattern of expression of MMR proteins in tumor tissue. This phenotype occurs in at least 20% of sporadic endometrial adenocarcinomas by epigenetic silencing of MLH1 gene. It is also observed in virtually all tumors occurring in patients with Lynch syndrome by monoallelic germline mutation in one of the MMR genes. The determination of this phenotype (dMMR vs. proficient MMR-pMMR) has therefore a pivotal place in the diagnosis algorithm for Lynch syndrome by monoallelic germline mutation in one of the MMR genes. The determination of this phenotype (dMMR vs. proficient MMR-pMMR) has therefore a pivotal place in the diagnosis algorithm for Lynch syndrome. We report the case of a woman with an early-onset endometrial adenocarcinoma who was suspected to be affected with Lynch syndrome based on tumor dMMR phenotype (MSI associated with loss of expression of MSH2 and MSH6 proteins). After complete germline and somatic evaluations, this phenotype was eventually explained by two MSH2 somatic mutations and the diagnosis of Lynch-like syndrome due to an unidentified MSH2 germline mutation was ruled out. Somatic mosaicism at low mutation rate was unlikely as no mutation was detected by DNA analysis from various tissue samples. Nevertheless, the three patient's children were tested for the two mutations and these tests were negative. Biallelic somatic mutations of one MMR gene is a mechanism of invalidation of the MMR system in sporadic cases. Clinicians have to be aware of this mechanism because of the great clinical implication for the patients and their relatives.


Assuntos
Adenocarcinoma/genética , Reparo de Erro de Pareamento de DNA/genética , Neoplasias do Endométrio/genética , Proteína 2 Homóloga a MutS/genética , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idade de Início , Proteínas de Ligação a DNA/metabolismo , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Imagem por Ressonância Magnética , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Proteína 2 Homóloga a MutS/metabolismo
18.
Fam Cancer ; 17(3): 469, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29071503

RESUMO

The article "Use of the BOADICEA Web Application in clinical practice: appraisals by clinicians from various countries" written by Anne Brédart · Jean­Luc Kop · Antonis C. Antoniou · Alex P. Cunningham · Antoine De Pauw ·Marc Tischkowitz · Hans Ehrencrona · Sylvie Dolbeault · Léonore Robieux · Kerstin Rhiem ·Douglas F. Easton · Peter Devilee · Dominique Stoppa­Lyonnet· Rita Schmutlzer, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 16th June 2017 without open access.

19.
Fam Cancer ; 17(1): 31-41, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28623477

RESUMO

The 'BOADICEA' Web Application (BWA) used to assess breast cancer risk, is currently being further developed, to integrate additional genetic and non-genetic factors. We surveyed clinicians' perceived acceptability of the existing BWA v3. An online survey was conducted through the BOADICEA website, and the British, Dutch, French and Swedish genetics societies. Cross-sectional data from 443 participants who provided at least 50% responses were analysed. Respondents varied in age and, clinical seniority, but mainly comprised women (77%) and genetics professionals (82%). Some expressed negative opinions about the scientific validity of BOADICEA (9%) and BWA v3 risk presentations (7-9%). Data entry time (62%), clinical utility (22%) and ease of communicating BWA v3 risks (13-17%) received additional negative appraisals. In multivariate analyses, controlling for gender and country, data entry time was perceived as longer by genetic counsellors than clinical geneticists (p < 0.05). Respondents who (1) considered hormonal BC risk factors as more important (p < 0.01), and (2) communicated numerical risk estimates more frequently (p < 0.001), judged BWA v3 of lower clinical utility. Respondents who carried out less frequent clinical activity (p < 0.01) and respondents with '11 to 15 years' seniority (p < 0.01) had less favourable opinions of BWA v3 risk presentations. Seniority of '6 to 10 years' (p < 0.05) and more frequent numerical risk communication (p < 0.05) were associated with higher fear of communicating the BWA v3 risks to patients. The level of genetics training did not affect opinions. Further development of BWA should consider technological, genetics service delivery and training initiatives.


Assuntos
Neoplasias da Mama/diagnóstico , Testes Genéticos , Aplicações da Informática Médica , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Estudos Transversais , Feminino , Predisposição Genética para Doença , Humanos , Análise Multivariada , Mutação , Medição de Risco/métodos
20.
Eur J Hum Genet ; 25(12): 1345-1353, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29255180

RESUMO

RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3) have recently been involved in breast and ovarian cancer predisposition: RAD51B, RAD51C, and RAD51D in ovarian cancer, RAD51B and XRCC2 in breast cancer. The aim of this study was to estimate the contribution of deleterious variants in the five RAD51 paralogs to breast and ovarian cancers. The five RAD51 paralog genes were analyzed by next-generation sequencing technologies in germline DNA from 2649 consecutive patients diagnosed with breast and/or ovarian cancer. Twenty-one different deleterious variants were identified in the RAD51 paralogs in 30 patients: RAD51B (n = 4), RAD51C (n = 12), RAD51D (n = 7), XRCC2 (n = 2), and XRCC3 (n = 5). The overall deleterious variant rate was 1.13% (95% confidence interval (CI): 0.72-1.55%) (30/2649), including 15 variants in breast cancer only cases (15/2063; 0.73% (95% CI: 0.34-1.11%)) and 15 variants in cases with at least one ovarian cancer (15/570; 2.63% (95% CI: 1.24-4.02%)). This study is the first evaluation of the five RAD51 paralogs in breast and ovarian cancer predisposition and it demonstrates that deleterious variants can be present in breast cancer only cases. Moreover, this is the first time that XRCC3 deleterious variants have been identified in breast and ovarian cancer cases.


Assuntos
Neoplasias da Mama/genética , Neoplasias Ovarianas/genética , Rad51 Recombinase/genética , Adulto , Idoso , Neoplasias da Mama/patologia , Proteínas de Ligação a DNA/genética , Feminino , Mutação em Linhagem Germinativa , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia
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