Información sobre riesgo, prevención, detección, síntomas, diagnosis, tratamiento y apoyo para el cáncer.
Información sobre el tratamiento del cáncer incluyendo quirúrgica, quimioterapia, radioterapia, estudios clínicos, terapia con protón, medicina complementaria avanzadas.
OncoLink se complace en ofrecer una amplia lista de lista completa de los agentes quimioterapéuticos más comúnmente usados??. Esta guía de referencia incluye información sobre la forma en que cada fármaco se administra, cómo funcionan, y los pacientes los efectos secundarios comunes pueden experimentar.
Maneras que los pacientes de cáncer y las personas que le cuidan puedan enfrentar el cáncer, los efectos secundarios, nutrición, cuestiones en general sobre el apoyo para el cáncer, duelo/decisiones sobre el termino de vida, y experiencias compartidas por sobrevivientes.
National Cancer Institute®
Ultima Vez Modificado: 1 de febrero del 2002
UI - 11732490
AU - Aktan-Collan K; Haukkala A; Mecklin JP; Uutela A; Kaariainen H
TI - Comprehension of cancer risk one and 12 months after predictive genetic testing for hereditary non-polyposis colorectal cancer.
SO - J Med Genet 2001 Nov;38(11):787-92
UI - 11746496
AU - Yarden RI; Brody LC
TI - Identification of proteins that interact with BRCA1 by Far-Western library screening.
SO - J Cell Biochem 2001;83(4):521-31
AD - Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Protein-protein interactions control numerous biological processes. In the case of a protein with no known function, identification of interacting proteins may lend insight into its cellular function. Protein-protein interactions are often detected by yeast two-hybrid screening which is based on a transcriptional read-out. One limitation of this technique is that transcription factors, when used as bait, frequently impair the effectiveness of this screen because they give rise to high levels of false positives. The carboxyl terminus of the breast cancer tumor suppressor gene, BRCA1, contains two BRCT motifs, a motif found in several DNA repair and cell cycle checkpoint proteins. This region of BRCA1 also exhibits an intrinsic transcriptional transactivation activity when bound to DNA as a fusion protein, thereby limiting its use in yeast two-hybrid screen. In order to isolate proteins that interact with this domain of BRCA1, we utilized a Far-Western screen, a method based on direct protein binding. We used recombinant histidine-tagged BRCT as the primary protein probe. We isolated eight cDNAs that bind to the BRCT domain of BRCA1. Further analysis demonstrated that two of the clones encode for proteins that interact directly with the BRCT domain of BRCA1. Copyright 2001 Wiley-Liss, Inc.
UI - 11788724
AU - Liu Q; Sommer SS
TI - Pyrophosphorolysis-activatable oligonucleotides may facilitate detection of rare alleles, mutation scanning and analysis of chromatin structures.
SO - Nucleic Acids Res 2002 Jan 15;30(2):598-604
AD - Departments of Molecular Genetics, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010-3000, USA.
Pyrophosphorolysis-activated polymerization (PAP) was initially developed to enhance the specificity of allele-specific PCR for detection of known mutations in the presence of a great excess of wild-type allele. The high specificity of PAP derives from the serial coupling of pyrophosphorolysis-mediated activation of a pyrophosphorolysis-activatable oligonucleotide (P*) followed by extension of the activated oligonucleotide. Herein, we demonstrate that genetically engineered DNA polymerases greatly improve the efficiency of PAP, making it a practical technique for detection of rare mutations. We also show that P* oligonucleotides have the novel and unexpected property of high sensitivity to mismatches throughout at least the 16 3'-terminal nucleotides. Thus, PAP constitutes a technology platform of potential utility whenever high specificity is required along the length of an oligonucleotide.
UI - 11788729
AU - Wilhelmsson LM; Norden B; Mukherjee K; Dulay MT; Zare RN
TI - Genetic screening using the colour change of a PNA-DNA hybrid-binding cyanine dye.
SO - Nucleic Acids Res 2002 Jan 15;30(2):E3
AD - Department of Physical Chemistry, Chalmers University of Technology, S-412 96 Gothenburg, Sweden.
As the relationship between human genes and various malfunctions and diseases becomes revealed at an ever-increasing pace, the need arises for the development of rapid genetic screening methods for diagnostic purposes. Genetic diseases show great diversity. Some are caused by a few characteristic localised mutations, while others arise from a large number of variations. Hence, it is unlikely that a single, general diagnostic method that applies to all cases will ever exist. Instead, a combination of methods is frequently applied. Here we propose the use of a dramatic colour change that a cyanine dye, 3,3'-diethylthiadicarbocyanine, displays upon binding to DNA-PNA duplexes. This method could become an inexpensive, fast and simple genetic screening test by visual inspection, with no need for complicated equipment. Our results demonstrate that this diagnostic method may be sufficiently sensitive to discriminate between even a fully complementary and a single mutation DNA sequence.
UI - 11521793
AU - Olopade OI; Pichert G
TI - Cancer genetics in oncology practice.
SO - Ann Oncol 2001 Jul;12(7):895-908
AD - University of Chicago Pritzker School of Medicine, Illinois, USA. email@example.com
Cancer is a genetic disease caused by the progressive accumulation of mutations in critical genes that control cell growth and differentiation. Completion of the Human Genome Project promises to revolutionize the practice of Medicine, especially Oncology care. The tremendous gains in the knowledge of the structure and function of human genes will surely impact the diagnosis, prognosis and treatment of cancer. Moreover, it will lead to more effective cancer control through the use of genetics to quantify individual cancer risks. This article reviews the current status of genetic testing and counseling for cancer risk assessment and will suggest a framework for integrating such counseling into oncology practice.
UI - 11720736
AU - Hussain SP; Hofseth LJ; Harris CC
TI - Tumor suppressor genes: at the crossroads of molecular carcinogenesis, molecular epidemiology and human risk assessment.
SO - Lung Cancer 2001 Dec;34 Suppl 2():S7-15
AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, 37 Convent Drive, MSC 4255, Bethesda, MD 20892, USA.
The p53 tumor suppressor gene is mutated in about half of all human cancer cases. The p53 protein modulates multiple cellular functions, such as gene transcription, DNA synthesis and repair, cell cycle arrest, senescence, and apoptosis. Mutations in the p53 gene can abrogate these functions and may lead to genetic instability and progress to cancer. The molecular archeology of the p53 mutation spectrum generates hypotheses concerning the etiology and molecular pathogenesis of cancer. The spectrum of somatic mutations in the p53 gene implicates environmental carcinogens and endogenous processes in the etiology of human cancer. The presence of a characteristic p53 mutation also can manifest a molecular link between exposure to a particular carcinogen and a specific type of human cancer, e.g. aflatoxin B1 (AFB1) exposure and codon 249ser mutations in hepatocellular carcinoma, ultraviolet (UV) exposure and CC to TT tandem mutations in skin cancer, and cigarette smoke and the prevalence of G to T transversions in lung cancer. Although several different exogenous carcinogens have been shown to selectively target p53, evidence supporting the endogenous insult of p53 from oxyradical and nitrogen-oxyradicals is accumulating. p53 mutations can be a biomarker of carcinogen effect. Determining the characteristic p53 mutation load in nontumorous tissue, with a highly sensitive mutation assay, can indicate a specific carcinogen exposure and also may help in identifying individuals at an increased risk of cancer.
UI - 11706616
AU - Royal Australian College of General Practitioners. National Preventive
TI - and Community Medicine Committee. Guidelines for preventive activities in general practice.
SO - Aust Fam Physician 2001 Oct;Spec No():S1i-xvi, S1-1-61
UI - 10885351
AU - Meijers-Heijboer EJ; Verhoog LC; Brekelmans CT; Seynaeve C;
TI - Tilanus-Linthorst MM; Wagner A; Dukel L; Devilee P; van den Ouweland AM; van Geel AN; Klijn JG Presymptomatic DNA testing and prophylactic surgery in families with a BRCA1 or BRCA2 mutation.
SO - Lancet 2000 Jun 10;355(9220):2015-20
AD - Department of Clinical Genetics, Erasmus University, Rotterdam, The Netherlands.
BACKGROUND: Germline mutations in the BRCA1 and BRCA2 genes highly predispose to breast and ovarian cancer. In families with BRCA1 or BRCA2 mutations, identification of mutation carriers is clinically relevant in view of the options for surveillance and prevention. METHODS: We assessed presymptomatic DNA testing and prophylactic surgery in 53 consecutive families presenting to the Rotterdam Family Cancer Clinic with a known BRCA1 or BRCA2 mutation. We identified predictors for DNA testing and prophylactic surgery with univariate and multivariate analysis. FINDINGS: 682 unaffected individuals with a 50% risk (275 women and 271 men) or with a 25% risk (136 women) for carrying a mutation were identified and offered a DNA test. Presymptomatic DNA testing was requested by 48% (198 of 411) of women and 22% (59 of 271) of men (odds ratio for difference between sexes 3.21 [95% CI 2.27-4.51]; p<0.001). In women, DNA testing was significantly more frequent at young age, in the presence of children, and at high pre-test genetic risk for a mutation. Of the unaffected women with an identified mutation who were eligible for prophylactic surgery, 51% (35 of 68) opted for bilateral mastectomy and 64% (29 of 45) for oophorectomy. Parenthood was a predictor for prophylactic mastectomy but not for prophylactic oophorectomy. Age was significantly associated with prophylactic oophorectomy, but not with prophylactic mastectomy, although there was a tendency towards mastectomy at younger ages. INTERPRETATION: In a clinical setting, we show a high demand for BRCA1 and BRCA2 testing by unaffected women at risk, and of prophylactic surgery by unaffected women with the mutation. Young women with children especially opt for DNA testing and prophylactic mastectomy.
UI - 11499060
AU - Frank TS; Critchfield GC
TI - Identifying and managing hereditary risk of breast and ovarian cancer.
SO - Clin Perinatol 2001 Jun;28(2):395-406
AD - Myriad Genetic Laboratories, Salt Lake City, Utah, USA. firstname.lastname@example.org
In the past, all women with a family history of breast or ovarian cancer were considered to be at increased risk of cancer themselves. The discovery of BRCA1 and BRCA2 demonstrated that susceptibility to breast and ovarian cancer can be inherited by women as a single-gene autosomal dominant disorder. For such women, evaluation of family history is an important screening tool to identify the possibility of hereditary cancer risk but only genetic testing can provide definitive, individualized risk assessment. Women who have inherited mutations in BRCA1 or BRCA2 now have several medical management options to address their increased risk of cancer. A well-educated community of health care providers and patients can use hereditary risk assessment, including genetic testing, to improve health care.
UI - 11499063
AU - McCabe LL; McCabe ER
TI - Postgenomic medicine. Presymptomatic testing for prediction and prevention.
SO - Clin Perinatol 2001 Jun;28(2):425-34
AD - Departments of Human Genetics and Pediatrics, UCLA School of Medicine, Los Angeles, California, USA.
Significant changes are occurring in genetic screening paradigms. Genetic screening is moving from traditional analytes, such as small molecules and proteins, to molecular genetic testing involving DNA and RNA. There are significant consequences to these changes, involving issues for the family unit, such as misattribution of parentage, and concerns regarding discrimination, confidentiality, and privacy. Although these latter issues have broader concerns for medicine and medical information, in the context of genetic testing, information derived from one individual can have a significant impact on others within their family. Screening is also changing from mendelian disease ascertainment to predictive testing. Issues that arise involve appropriate age at testing for adult-onset disorders, the clinical validity and clinical use of genetic testing for complex diseases, and the efficacy of interventions following genetic testing. We are also learning that the phenotypes of even simple mendelian disorders are influenced by complex genetic and environmental factors. The observations that genotypes rarely predict phenotypes absolutely have significant ramifications for counseling based on mutation analysis, for example in neonates who have not yet manifested symptoms and in older children and in adults undergoing predictive testing. Molecular genetic testing often proceeds rapidly from the research laboratory to the clinical setting. We must recognize that for single-gene disorders with high penetrance, the information derived from such testing may be relatively easy to interpret and apply. For complex diseases, however, the populations studied and their demographic characteristics are extremely important for extrapolation to counseling of individual patients. The value of population-based predictive testing is exemplified by newborn screening. It is clear that the Human Genome Project, and the information and technologies from it, will have a much broader impact on public health by presymptomatic prediction and prevention of disease.
UI - 11209389
AU - Skirton H; Patch C
TI - The 'new genetics' and nursing: what does it have to do with me?
SO - Nurs Stand 2000 Jan 26-Feb 1;14(19):42-6
AD - Clinical Genetics Unit Taunton and Somerset NHS Trust.
Recent developments in genetics mean that this previously specialised subject is now essential knowledge for all nurses. Heather Skirton and Christine Patch describe how fundamental knowledge of the new genetics will enable nurses to help patients through the maze of choices open to them.
UI - 11677941
AU - Kobayashi S; Ochiai T; Hori S; Suzuki T; Shimizu T; Gunji Y; Shimada H;
TI - Yamamoto S; Ogawa A; Kohno Y; Sunaga M; Shimazu M; Tanaka K Copper metabolism after living donor liver transplantation for hepatic failure of Wilson's disease from a gene mutated donor.
SO - Hepatogastroenterology 2001 Sep-Oct;48(41):1259-61
AD - Department of Academic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuoh-ku, Chiba 260-8670, Japan. email@example.com
There is a genetic problem in living donor liver transplantation, involving Wilson's disease, because the majority of donors have a kinship relationship. Recently, it was reported that the serum ceruloplasmin level is insufficient in some persons with one allele mutation. The recipient was a 13-year-old male child, and the donor was a 22-year-old woman, who was his sister by a different father. The gene analysis for Wilson's disease (ATP7B gene) was preoperatively carried out by the amplification refractory mutation system-PCR. Homozygous and heterozygous deletion of 2871 cytosine (C) were detected in the recipient and donor, respectively, in the ATP7B gene. Serum ceruloplasmin level was sufficient in the donor. The right hepatic lobe graft was transplanted to the recipient. Immediately after the liver transplantation, the copper metabolism improved to increase the serum ceruloplasmin levels up to the normal range, and decrease the urinary copper excretion. However, the serum ceruloplasmin levels gradually decreased below the normal base line, although the urine copper levels continued to be low without any clinical symptoms. We should perform gene analyses and confirm the serum ceruloplasmin levels in donors before living donor liver transplantation for Wilson's disease, to screen for their impairment of copper metabolism. After living donor liver transplantation for Wilson's disease, we should carefully follow-up the transition of serum ceruloplasmin levels in the recipient.
UI - 11753744
AU - Yildiz Y; Matern S; Lammert F
TI - [Screening for hereditary pancreatic carcinoma]
SO - Dtsch Med Wochenschr 2001 Dec 21;126(51-52):1479-80
AD - Medizinische Klinik III, Universitatsklinikum der RWTH Aachen.
UI - 11787135
AU - Kaariainen H
TI - [Risks and adverse effects of genetic screening]
SO - Duodecim 2000;116(8):909-13
AD - Vaestoliiton perinnollisyysklinikka PL 849, 00101 Helsinki. firstname.lastname@example.org
UI - 11789512
AU - Gevers S
TI - Medical examinations preceding employment and/or private insurance: a proposal for European guidelines.
SO - Eur J Health Law 2000 Jun;7(2):145-72
AD - University of Amsterdam.
UI - 11789513
AU - Bottis MC
TI - Comment on a view favoring ignorance of genetic information: confidentiality, autonomy, beneficence and the right not to know.
SO - Eur J Health Law 2000 Jun;7(2):173-83
AD - Ionian University, Greece.
UI - 11789514
AU - Laurie GT
TI - Protecting and promoting privacy in an uncertain world: further defences of ignorance and the right not to know.
SO - Eur J Health Law 2000 Jun;7(2):185-91
AD - Faculty of Law, University of Edinburgh, Scotland.
UI - 11802208
AU - de la Hoya M; Osorio A; Godino J; Sulleiro S; Tosar A; Perez-Segura P;
TI - Fernandez C; Rodriguez R; Diaz-Rubio E; Benitez J; Devilee P; Caldes T Association between BRCA1 and BRCA2 mutations and cancer phenotype in Spanish breast/ovarian cancer families: implications for genetic testing.
SO - Int J Cancer 2002 Feb 1;97(4):466-71
AD - Laboratory of Molecular Oncology, Hospital Universitario San Carlos, Madrid, Spain.
Index cases from a clinically relevant cohort of 102 Spanish families with at least 3 cases of breast and/or ovarian cancer (at least 1 case diagnosed before age 50) in the same lineage were screened for germline mutations in the entire coding sequence and intron boundaries of the breast cancer susceptibility genes BRCA1 and BRCA2. Overall, the prevalence of mutations was 43% in female breast/ovarian cancer families, 15% in female breast cancer families and 100% in male breast cancer families. Three recurrent mutations (185delAG, 589delCT and A1708E) explained 63% of BRCA1-related families. Early age at diagnosis of breast cancer, ovarian cancer, bilateral breast cancer, concomitant breast/ovarian cancer in a single patient and prostate cancer but not unilateral breast cancer were associated with BRCA1 and BRCA2 mutations. Male breast cancer was associated with BRCA2 mutations. The presence of male breast cancer was the only cancer phenotype that distinguished BRCA2- from BRCA1-related families. We have developed a logistic regression model for predicting the probability of harbouring a mutation in either BRCA1 or BRCA2 as a function of the cancer phenotype present in the family. The predictive positive and negative values of this model were 77.4% and 79%, respectively (probability cutoff of 30%). The findings of our work may be a useful tool for increasing the cost-effectiveness of genetic testing in familial cancer clinics. Copyright 2001 Wiley-Liss, Inc.
UI - 11802209
AU - Meindl A; German Consortium for Hereditary Breast and Ovarian Cancer
TI - Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population.
SO - Int J Cancer 2002 Feb 1;97(4):472-80
AD - Department of Medical Genetics, Ludwig-Maximilians University, Munich, Germany. email@example.com
The main focus of this German-wide multi-center study was to establish a BRCA1/2 mutation profile and to determine family types with high frequencies of mutations in these genes. In a comprehensive study, the entire coding sequences of the breast cancer genes BRCA1 and BRCA2 were analyzed in 989 unrelated patients from German breast/ovarian cancer families. A total of 77 BRCA1 and 63 BRCA2 distinct deleterious mutations were found in 302 patients. More than (1/3) of these mutations are novel and might be specific for the German population. Eighteen common mutations were found in 68% of cases in BRCA1 and 13 recurrent mutations in 44% of cases in BRCA2, facilitating prescreening approaches. Haplotype analysis indicate that 14 out of 20 recurrent mutations are likely originating from a common founder. An additional 50 different rare sequence variants with unknown relevance for tumorigenesis were found in 72 families. Correlation of BRCA1/BRCA2 detection rates with family history identified families with both breast and ovarian cancer to be at highest risk for BRCA1/BRCA2 mutations (43% and 10%, respectively), followed by families with at least 2 premenopausal cases of breast cancer (24% BRCA1 and 13% BRCA2 mutations). These data provide strong evidence for further predisposing genes in the German population. In breast cancer families with 2 or 3 affected females but only a single or no premenopausal case, mutations were detected with low frequencies (about 10% or less for both genes). The decision for or against molecular diagnosis is now aided by considering the expected mutation detection rates that greatly depend on family history and structure. Copyright 2001 Wiley-Liss, Inc.
UI - 11826460
AU - Levin T; Reichelt J; Heimdal K; Moller P
TI - [Information to families with hereditary breast and ovarian cancer]
SO - Tidsskr Nor Laegeforen 2001 Nov 20;121(28):3292-4
AD - Seksjon for genetisk veiledning Avdeling for kreftgenetikk Det Norske Radiumhospital 0310 Oslo. firstname.lastname@example.org
BACKGROUND: Under Norwegian legislation, persons at risk should make the initial contact with the proper health personnel, and not vice versa. It may be argued that the physician should be allowed to make contact with persons at risk of preventable or curable disorders. MATERIAL AND METHODS: We identified all first-degree relatives of all 75 BRCA1 mutation carriers diagnosed within a given period of time and asked them whether or not they had been informed by their relatives. RESULTS: After two years, 60/63 (95%) adult sisters and daughters had made contact with us; the remaining three (5%) had been informed. In comparison, 18/45 (40%) adult brothers and sons had contacted us. INTERPRETATION: The legislation constituted no barrier to offering health services to the target group. Information on our services had reached all close relatives who could benefit from them. This may be representative for curable inherited disorders. We examined inherited cancer limited to females; similar studies on inherited cancers in males and on other curable inherited disorders should be performed. Outside the framework of the present study, we are aware of rare examples of distant cousins who have not been properly informed through their families. One legally acceptable way of identifying mutation carrier families is to test all patients with breast or ovarian cancer for causative mutations. Health services should be monitored to make future decisions based on empirical evidence.
UI - 11810084
AU - Hebert-Blouin MN; Koufogianis V; Gillett P; Foulkes WD
TI - Fallopian tube cancer in a BRCA1 mutation carrier: rapid development and failure of screening.
SO - Am J Obstet Gynecol 2002 Jan;186(1):53-4
AD - Department of Medicine, McGill University Health Centre, McGill University, Montreal, Quebec, Canada.
We report a case of fallopian tube cancer that developed in a woman with a germ-line BRCA1 mutation. The notable feature of this case was the extremely rapid growth of the cancer, which precluded early diagnosis. Preventive gynecologic surgery in BRCA1/2 mutation carriers should probably always include bilateral salpingectomy.
UI - 11795428
AU - Hittelman WN
TI - Genetic instability in epithelial tissues at risk for cancer.
SO - Ann N Y Acad Sci 2001 Dec;952():1-12
AD - Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. email@example.com
Epithelial tumors develop through a multistep process driven by genomic instability frequently associated with etiologic agents such as prolonged tobacco smoke exposure or human papilloma virus (HPV) infection. The purpose of the studies reported here was to examine the nature of genomic instability in epithelial tissues at cancer risk in order to identify tissue genetic biomarkers that might be used to assess an individual's cancer risk and response to chemopreventive intervention. As part of several chemoprevention trials, biopsies were obtained from risk tissues (i.e., bronchial biopsies from chronic smokers, oral or laryngeal biopsies from individuals with premalignancy) and examined for chromosome instability using in situ hybridization. Nearly all biopsy specimens show evidence for chromosome instability throughout the exposed tissue. Increased chromosome instability was observed with histologic progression in the normal to tumor transition of head and neck squamous cell carcinomas. Chromosome instability was also seen in premalignant head and neck lesions, and high levels were associated with subsequent tumor development. In bronchial biopsies of current smokers, the level of ongoing chromosome instability correlated with smoking intensity (e.g., packs/day), whereas the chromosome index (average number of chromosome copies per cell) correlated with cumulative tobacco exposure (i.e., pack-years). Spatial chromosome analyses of the epithelium demonstrated multifocal clonal outgrowths. In former smokers, random chromosome instability was reduced; however, clonal populations appeared to persist for many years, perhaps accounting for continued lung cancer risk following smoking cessation.
UI - 11807889
AU - Hughes C; Lerman C; Schwartz M; Peshkin BN; Wenzel L; Narod S; Corio C;
TI - Tercyak KP; Hanna D; Isaacs C; Main D All in the family: evaluation of the process and content of sisters' communication about BRCA1 and BRCA2 genetic test results.
SO - Am J Med Genet 2002 Jan 15;107(2):143-50
AD - Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. firstname.lastname@example.org
Despite the potential importance of family communication, little is known about the process and content of communicating BRCA1/2 test results to relatives. The objectives of this observational study were to describe the process and content of communicating BRCA1/2 test results to sisters, and to evaluate whether the proband's carrier status influenced communication outcomes. Participants were 43 women who were the first family member to have genetic testing (probands). Probands reported on communication outcomes for 81 sisters. Process and content variables were evaluated 1-month after receipt of BRCA1/2 test results using the Family Communication Questionnaire (FCQ). Overall, BRCA1/2 test results were communicated to 85% of sisters, and carriers communicated their results to significantly more sisters compared to uninformative (96% vs. 76%, FET = 0.02). The most important reason for communicating results was to provide genetic risk information; however, compared to uninformatives, carriers communicated their results to significantly more sisters to obtain emotional support (74%) and to get advice about medical decisions (42%) (FET = 0.001). Carriers also discussed the possibility of discrimination and recommendations for cancer management with significantly more sisters. Among sisters to whom BRCA1/2 test results were not communicated, the most important reason for not sharing test results was because of emotionally distant relationships. The results of this study suggest that probands are likely to quickly communicate their BRCA1/2 test results to relatives and that although needs for social support may motivate family communication, emotionally distant relationships may be a barrier to communication with relatives. Copyright 2001 Wiley-Liss, Inc.
UI - 11682322
AU - Surbone A
TI - Ethical implications of genetic testing for breast cancer susceptibility.
SO - Crit Rev Oncol Hematol 2001 Nov;40(2):149-57
AD - Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. email@example.com
The identification of gene mutations involved in hereditary breast cancer is a major recent scientific discovery, enabling us to identify women at very high risk, and also providing the means to understand the biology of breast cancer and to explore novel preventive strategies. Yet, it carries medical, psychological, ethical and social implications. This paper is a review of all the ethical implications of genetic testing for breast cancer predisposition, as well as an attempt to discuss the more philosophical questions of women facing BRCA testing. To what extent does the individual benefit from genetic knowledge? Some women look with trepidation upon the potential of planning their life in view of a risk, while others believe that only through knowledge and awareness we can improve control of our life. The risk of breast cancer may be qualitatively so important to justify all the potential risks of finding out about it.
UI - 11809257
AU - Ahr A; Karn T; Solbach C; Seiter T; Strebhardt K; Holtrich U; Kaufmann M
TI - Identification of high risk breast-cancer patients by gene expression profiling.
SO - Lancet 2002 Jan 12;359(9301):131-2
We previously used DNA array analyses in the molecular profiling of breast cancers. By cluster analysis of 55 patients, we identified a subpopulation of breast cancers-designated class A-that contained a high number of nodal-positive tumours and that had frequently developed distant metastases at the time of diagnosis. We have now analysed follow-up data from these patients. We found that, despite a median of only 23.5 months of follow-up, 11 of 22 patients in class A progressed to metastatic disease, and three of five patients classified as having a nodal status of N0 in this subpopulation developed distant metastases. Our analysis identifies breast-cancer patients with a high risk of disease recurrence, and could act as a first step towards improved patient-adapted therapy.
UI - 11813762
AU - Hailey BJ; Carter CL; Burnett DR
TI - Breast cancer attitudes, knowledge, and screening behavior in women with and without a family history of breast cancer.
SO - Health Care Women Int 2000 Dec;21(8):701-15
AD - Department of Psychology, The University of Southern Mississippi, Hattiesburg 39406-5025, USA. firstname.lastname@example.org
Women volunteers with or without a first-degree relative with breast cancer (FDR) were compared on several measures. Relative to the comparison group, women in the FDR group had more negative attitudes about breast cancer (including more anxiety about breast cancer), viewed their risk for getting breast cancer as greater (although they underestimated the actual risk), and were more likely to engage in appropriate screening behavior. A high percentage of women in both groups stated that they would want to have a genetic test for breast cancer if it were generally available.
UI - 11786931
AU - Majores M; Kolsch H; Bagli M; Papassotiropoulos A; Lohmann PL; Schmitz
TI - S; Rao ML; Maier W; Heun R Cathepsin D: screening for new polymorphisms using single-strand conformation polymorphism analysis.
SO - Int J Mol Med 2002 Feb;9(2):185-7
AD - Department of Psychiatry, University of Bonn, D-53105 Bonn, Germany.
Cathepsin D (CTSD) is a lysosomal protease involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer's disease (AD). Previous findings revealed a significant association between the T allele of the 224 C/T (A58V) polymorphism in exon 2 of the CTSD gene and late onset AD. The exonic regions of the CTSD gene were screened for further polymorphic variations using polymerase chain reaction and single-strand conformation polymorphism analysis. In addition to the known 224 C/T polymorphism and two silent mutations in exons 3 and 4 we detected two new polymorphisms in introns 5 and 8. Combination of these sequence variations results in three different haplotypes; one of these haplotypes is due to the new polymorphism in intron 5. We detected no further missense mutations except for the known 224 C/T polymorphism in exon 2. Thus, if sequence variations within the CTSD gene influence the risk for various diseases, the pathogenic mechanism is likely to be linked to the amino acid substitution in the profragment of CTSD.
UI - 11817609
AU - Neumann E; Kullmann F; Judex M; Justen HP; Wessinghage D; Gay S;
TI - Scholmerich J; Muller-Ladner U Identification of differentially expressed genes in rheumatoid arthritis by a combination of complementary DNA array and RNA arbitrarily primed-polymerase chain reaction.
SO - Arthritis Rheum 2002 Jan;46(1):52-63
AD - University of Regensburg, Germany.
OBJECTIVE: There is increasing evidence that T cell-independent pathways, such as the up-regulation of protooncogenes and the production of growth factors and matrix-degrading enzymes, lead to progressive destruction of affected joints. Therefore, identification of differentially regulated genes restricted to rheumatoid arthritis (RA) synovial fibroblasts is essential. A combination of RNA arbitrarily primed-polymerase chain reaction (RAP-PCR) and complementary DNA (cDNA) array with defined genes was used for a highly sensitive differential screening using small amounts of RNA. METHODS: RNA was extracted from cultured synovial fibroblasts obtained from 6 patients with RA and 6 patients with osteoarthritis (OA). RAP-PCR was performed using different arbitrary primers for first- and second-strand synthesis. PCRs were hybridized to cDNA array membranes. RA samples were compared with OA samples for differentially expressed genes. RESULTS: In contrast to standard cDNA array, the identification of 12 differentially expressed genes in RA compared with OA (approximately 6%) was possible. Differentially expressed genes of interest were confirmed using semiquantitative RT-PCR and in situ hybridization. CONCLUSION: Numerous variants of the differential display method and continuous improvements, including RAP-PCR, have proven to be both efficient and reliable for examining differentially regulated genes. Our results show that RAP-PCR combined with cDNA arrays is a suitable method for identifying differentially expressed genes in rheumatoid synovial fibroblasts, using very small amounts of RNA.
UI - 11822793
AU - Cappelli M; Surh L; Humphreys L; Verma S; Logan D; Hunter A; Allanson J
TI - Measuring women's preferences for breast cancer treatments and BRCA1/BRCA2 testing.
SO - Qual Life Res 2001;10(7):595-607
AD - Children's Hospital of Eastern Ontario, Ottawa, Canada. email@example.com
In establishing decision models in the treatment and prevention of breast cancer, it is important to evaluate patients' preferences for such interventions. The objectives of the present study were: (i) to characterize women's preferences for breast cancer treatments and BRCA1/BRCA2 testing, using the rating scale and standard gamble techniques; and (ii) to identify factors associated with these quality of life indices. Data were collected from women with breast cancer (n = 60), high-risk relatives of women with breast cancer (n = 58), and women in the general population (n = 51). Regardless of group membership, participants favoured treatment and prevention options that involved minimal physical invasiveness. Women with breast cancer rated lumpectomy and radiation treatment more highly than high-risk relatives and women in the general population. Preferences did not differ according to participants' intentions to undergo BRCA testing. Age was the only demographic variable associated with health state preferences. These findings hold implications for the application of patient preferences to clinical decision making.
UI - 11822420
AU - Merle JC; European Group on Ethics in Science and New Technologies
TI - The weakness of the intention to be uncontroversial on controversial issues.
SO - Biomed Ethics 2000;5(2):64-9
AD - Faculty of Philosophy, University of Tuebingen.
UI - 10714658
AU - Brassat D; Camuzat A; Vidailhet M; Feki I; Jedynak P; Klap P; Agid Y;
TI - Durr A; Brice A Frequency of the DYT1 mutation in primary torsion dystonia without family history.
SO - Arch Neurol 2000 Mar;57(3):333-5
AD - Federation de Neurologie, INSERM U289, Hopital de la Salpetriere, Paris, France.
BACKGROUND: Idiopathic torsion dystonia is a clinically and genetically heterogeneous movement disorder. A GAG deletion at position 946 of the DYT1 gene was the first mutation found, in early-onset dystonia, with an autosomal dominant transmission and reduced penetrance. OBJECTIVE: To evaluate the frequency of the DYT1 mutation in patients with idiopathic torsion dystonia but without a family history. DESIGN: Prospective cohort study. SETTING: Four botulinum toxin clinics in the Paris, France, area. PATIENTS: A French population of 100 patients with dystonia. MAIN OUTCOME: Frequency of the DYT1 mutation tested by polymerase chain reaction and enzyme restriction analysis for the 946 GAG deletion, and genotype-to-phenotype correlation. RESULTS: Only 5 mutation carriers were identified, 4 of whom were part of a group of 10 patients with generalized dystonia. Onset was between ages 5 and 12 years as in typical early-onset dystonia. All 4 patients had cranial muscle involvement, which is atypical for DYT1 mutation carriers. One had segmental dystonia. Molecular analysis of relatives in 2 families demonstrated that the lack of family history was due to reduced penetrance. CONCLUSIONS: For accurate diagnosis and genetic counseling, screening for the DYT1 deletion is of great interest in cases with generalized dystonia without a family history. In other cases, positive results are rare.
UI - 11426564
AU - Einsiedel HG; Taube T; Beyermann B; Dragon S; Moricke A;
TI - Kebelmann-Betzig C; Kochling J; Henze G; Seeger K Absence of mutations in the CDKN2 binding site of CDK4 in childhood acute lymphoblastic leukemia.
SO - Leuk Lymphoma 2001 Jan;40(3-4):413-7
AD - Department of Pediatric Oncology/Hematology, Charite Campus Virchow Klinikum, Humboldt-University Berlin, Germany.
The cell cycle regulatory circuit resulting in phosphorylation of the retinoblastoma protein (pRB) is frequently altered in human cancers. Several mechanisms of disruption are known in that pathway. In childhood acute lymphoblastic leukemia (ALL), the main disrupting mechanism is the homozygous deletion of the CDKN2 (cyclin dependent kinase inhibitor 2) genes: p16CDKN2a, p15CDKN2b, and p19ARF. Another pRB pathway disturbance is a previously described point mutation in the exon 2 of CDK4, a pRB phosphorylating enzyme, which abrogates binding of the latter to its inhibitors, p16CDKN2a and p15CDKN2b. Here we report the absence of point mutations in the CDKN2-binding site of CDK4 in 100 cases of childhood ALL, 2 cases of childhood chronic myeloid leukemia and 9 hematologic cell lines screened by PCR-SSCP (polymerase chain reaction single stranded conformational polymorphism gel electrophoresis), thereby minimizing the possibility of the existence of these specific CDK4 mutations in childhood ALL.
UI - 11705864
AU - Ikonen T; Matikainen M; Mononen N; Hyytinen ER; Helin HJ; Tommola S;
TI - Tammela TL; Pukkala E; Schleutker J; Kallioniemi OP; Koivisto PA Association of E-cadherin germ-line alterations with prostate cancer.
SO - Clin Cancer Res 2001 Nov;7(11):3465-71
AD - Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere, P.O. Box 607, FIN-33101 Tampere, Finland. firstname.lastname@example.org
In our recent cancer registry-based study, the incidence of gastric carcinoma was increased up to 5-fold in male relatives of early-onset prostate cancer (PCA) patients. This association may reflect the influence of genetic factors predisposing individuals to both tumor types. Germ-line mutations of the CDH1 gene at 16q have recently been associated with familial gastric cancer. Furthermore, two genome-wide linkage studies of PCA recently reported positivity at 16q. We therefore identified families and individual patients with both gastric and PCA and investigated whether the CDH1 gene mutations were involved in cancer predisposition in these cases. Fifteen of the 180 Finnish hereditary PCA families (8.3%) had one or more gastric cancer cases. No truncating or splice site CDH1 mutations were identified by PCR single-strand conformational polymorphism in these families or in eight individual patients who had both prostate and gastric cancer. However, a novel S270A missense mutation in exon 6 of the CDH1 gene was seen in a single family with four prostate and two gastric cancers. A large-scale population-based survey indicated a higher prevalence of S270A among both familial PCA cases (3.3%; n = 120; P = 0.01) and unselected PCA patients (1.5%; n = 472; P = 0.12) as compared with blood donors serving as population controls (0.5%; n = 923). We conclude that individual rare mutations and polymorphisms in the CDH1 gene, such as S270A, may contribute to the onset of PCA and warrant further investigations in other populations. However, the CDH1 gene does not appear to explain the link between prostate and gastric cancer.
UI - 11730630
AU - Roman R; Colomer A; Erill N; Puig X; Guix M
TI - [Importance of 5569G/A polymorphism in intron 4 of HFE gene in the diagnosis of hereditary hemochromatosis]
SO - Med Clin (Barc) 2001 Dec 1;117(18):690-1
AD - BIOPAT, Biopatologia Molecular, Grup Assistencia, Hospital de Barcelona, Barcelona, Spain.
BACKGROUND: The presence of the 5569A polymorphism may lead to misdiagnosis of patients susceptible of hereditary hemochromatosis (HH). For that reason, samples containing the Cys282Tyr mutation were revised and the frequency of this polymorphism in our environment was assessed. PATIENTS AND METHOD: Twenty samples were retested and 56 controls were included. The study was performed by PCR-RFLP. RESULTS: The diagnosis was confirmed in 8 cases susceptible of error. However, an amplification deficiency of normal alleles was detected in 2 heterozygous (17%). The allelic frequency of the 5569A polymorphism in the control population was 14.3%. CONCLUSIONS: Although misdiagnosis was not committed, we recommend changing to any primer that does not include the 5569G/A polymorphism in the study of HH.
UI - 11796012
AU - He J; Zhou G; Liu KD; Qin XY
TI - Construction and preliminary screening of a human phage single-chain antibody library associated with gastric cancer.
SO - J Surg Res 2002 Feb;102(2):150-5
AD - Department of Surgery, Fudan University, Shanghai 200032, People's Republic of China.
BACKGROUND: The aim of this study was to construct a phage library of human single-chain antibodies associated with gastric cancer and screen such a library for CEA binding scFv. MATERIALS AND METHODS: The cDNA library of antibody variable regions was constructed using mRNA from metastatic lymph nodes or spleen of patients with stomach cancer by RT-PCR. These cDNA were assembled into a single-chain format and cloned into phagemid pCANTAB-5 and then transformed into Escherichia coli TG1. The scFv gene library was rescued by M13KO7 helper phage. CEA and the viable CEA-positive gastric cancer cell line MKN-28 were used to screen the phage antibody library. Indirect and tumor cell ELISA was used to determine the specificity of phage antibody. Fixed cell immunofluorescence and live cell FACS analysis were used to further characterize the binding of phage scFv. RESULTS: After transformation into E. coli TG1, 2.5 x 10(7) cfu/microg ampicillin-resistant clones grew. Sequences of tho
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