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Search Results: 1 - 10 of 468872 matches for " Steven A Narod "
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Regarding the Use of Tamoxifen Post-Oophorectomy to Prevent Hereditary Breast Cancer
Steven A Narod
Hereditary Cancer in Clinical Practice , 2006, DOI: 10.1186/1897-4287-4-4-167
Abstract: Metcalfe et al. conducted a historical cohort study on 491 women with a BRCA1 or BRCA2 mutation who were followed for contralateral breast cancer [6]. The combination of tamoxifen and oophorectomy was particularly effective in women under 50; the hazard ratio associated with this combination of therapy was 0.09 (95% CI, 0.01 to 0.68; P = 0.02).In a matched case-control study, Gronwald et al. studied 285 women with bilateral breast cancer and a BRCA1 or BRCA2 mutation, and 751 control women with unilateral breast cancer and a BRCA1 or BRCA2 mutation [7]. The use of tamoxifen for treating the first breast cancer was compared between bilateral and unilateral cases. The multivariate odds ratio for contralateral breast cancer associated with tamoxifen use was 0.50 for carriers of BRCA1 mutations and was 0.42 for carriers of BRCA2 mutations. However, in contrast to Metcalfe's study, the protective effect of tamoxifen was not present among women who had undergone an oophorectomy (OR = 0.83). However, this subgroup was small and the confidence interval was wide (95%CI, 0.24-2.89). A strong protective effect of tamoxifen was apparent among women who had undergone natural menopause (OR = 0.44; 95% CI, 0.27-0.65).Should tamoxifen be given to women with mutations who have had an oophorectomy? Clearly, more data are needed. In women over 50, or who had an oophorectomy after natural menopause, tamoxifen should be effective. In young women (<50) following surgical menopause, the data are less clear-cut, but I think the drug should be considered. Factors to take into consideration when making this decision should include the estimate of the residual lifetime risk of cancer, the woman's level of interest in mastectomy (there is no point in giving tamoxifen to healthy women after prophylactic mastectomy), the presence of an intact uterus (i.e., risk of endometrial cancer) and access to MRI screening facilities.
Screening for BRCA1 and BRCA2 mutations in breast cancer patients from mexico: the public health perspective
Narod,Steven A;
Salud Pública de México , 2009, DOI: 10.1590/S0036-36342009000800009
Abstract: genetic testing for mutations in brca1 and brca2 has potentially important public health implications. through judicious testing of women believed to be at high risk for early-onset breast cancer and for ovarian cancer, it is possible to identify highly-predisposed women prior to the development of cancer. current preventive options include preventive mastectomy, preventive oophorectomy, tamoxifen and oral contraceptives. the ability to offer genetic testing in mexico on a widespread level is enhanced if the common founder mutations in the two genes can be discovered or if the cost of genetic sequencing is reduced. it is important that a genetic testing service be a multi-disciplinary effort with co-ordinated follow-up.
Predisposición genética para el cáncer de mama: genes BRCA1 y BRCA2
Narod,Steven A; Rodríguez,Adriana A;
Salud Pública de México , 2011, DOI: 10.1590/S0036-36342011000500010
Abstract: the discovery of genes brca1 and brca2 has led to the introduction of genetic tests more complex every time for the evaluation ofthehereditarycancerrisk,amongothers.in the present paper we explore the criteria to decide when to run the testing for the genes, as well as the implications for the treatment of patients who are identified with them.
A common missense variant in BRCA2 predisposes to early onset breast cancer
Bohdan Górski, Steven A Narod, Jan Lubiński
Breast Cancer Research , 2005, DOI: 10.1186/bcr1338
Abstract: We genotyped 3,241 cases of breast cancer diagnosed at under 51 years of age, unselected for family history, from 18 hospitals throughout Poland and 2,791 ethnic-matched controls for a single BRCA2 C5972T variant.The variant was present in approximately 6% of the Polish population. In the study, 13 women (11 cases and two controls (OR = 4.7; p = 0.02)) were homozygous for the variant allele. The overall odds ratio for breast cancer in women with a single copy of the BRCA2 C5972T variant was 1.1 (p = 0.7); however, the effect was significant for patients diagnosed at or before age 40 (OR = 1.4; p = 0.04). We reviewed the association between the BRCA2 variant in different histologic subgroups and found the effect most pronounced in women who had ductal carcinoma in situ (DCIS) with micro-invasion (OR = 2.8; p < 0.0001).The BRCA2 C5972T allele is a common variant in Poland that increases the risk of DCIS with micro-invasion. The homozygous state is rare but increases the risk of breast cancer five-fold.There are several approaches to identifying low-penetrance candidate genes for breast cancer. In one approach, it is assumed that missense variants of genes for which truncating mutations are clearly pathogenic might also be deleterious. If the missense allele demonstrates high penetrance (i.e. like truncating mutations), then it will be relatively straightforward to establish the association when allele frequency is high. If the penetrance of the missense variant is low, however, then the association may be missed if only a small number of cancers is studied and the variant may falsely be classified as a neutral polymorphism. We are in the process of establishing a large database of breast cancer cases and ethnic-matched controls in order to evaluate the pathogenicity of the common founder alleles of the most important cancer susceptibility genes. Several deleterious founder alleles have been identified in BRCA1, but to date, no founder mutation in BRCA2 has been identi
Cisplatin in breast cancer treatment in BRCA1 carriers
Gronwald Jacek,Byrski Tomasz,Lubinski Jan,Narod Steven A
Hereditary Cancer in Clinical Practice , 2012, DOI: 10.1186/1897-4287-10-s4-a17
The Prevention of Hereditary Breast and Ovarian Cancer: A Personal View
Steven Narod
Hereditary Cancer in Clinical Practice , 2004, DOI: 10.1186/1897-4287-2-1-5
Abstract: It is nearly ten years since the BRCA1 gene was identified and genetic testing for breast cancer susceptibility is now widespread. During the last ten years we have come to accept that genetic testing can be done outside of research settings, that most women wish to have - and are capable of understanding - personal information about the risks and benefits of genetic testing and that routine pre-test psychological counselling is not mandatory. As a group, women do not suffer unduly from anxiety or depression following the receipt of a positive test result [1] (although we all know of exceptions to this rule). There is still uncertainty about the best estimate to give a carrier for her risks of breast and ovarian cancer. Some argue that different carriers should be given different risks depending on their family history, but this individualized approach to counselling is really too complicated to be practical. But we all agree that the risks are unacceptably high and that something needs to be done to lower them.It was a relatively straightforward task to establish that prophylactic mastectomy is effective. This has been shown in a small prospective study [2], and in historical cohort studies of primary [3] and contralateral [4] breast cancers. Here the data is consistent. Meijers-Heijboer and colleagues observed no case of breast cancer among 76 women who underwent prophylactic mastectomy after a mean follow-up of three years [2]. Metcalfe and colleagues studied 491 women treated for hereditary breast cancer [4]. Only one contralateral breast cancer was observed among 146 women who had undergone a contralateral mastectomy, versus 42 expected (p < 0.0001). Some debate remains about the optimal age of prophylactic mastectomy and about the best techniques for mastectomy and for reconstruction, but there are few who would argue against the effectiveness of the procedure. But our aim is to replace prophylactic mastectomy with something better. This will either come from
Epidemiología descriptiva y genética molecular del cáncer de mama hereditario en Costa Rica Descriptive epidemiology and molecular genetics of hereditary breast cancer in Costa Rica
Laura García-Jiménez,Gustavo Gutiérrez-Espeleta,Steven A. Narod
Revista de Biología Tropical , 2012,
Abstract: El cáncer de mama ocupa el primer lugar en incidencia y mortalidad entre las mujeres costarricenses, para el a o 2011, se tiene una proyección de 1 071 casos nuevos. Mediante selección directa se reclutaron 116 pacientes diagnosticadas con cáncer de mama y con antecedentes familiares de esta enfermedad. Se analizó la prevalencia de los factores de riesgo y de las mutaciones en los genes BRCA1 y BRCA2. Se encontró que la edad promedio de las mujeres portadoras de una mutación es menor que en mujeres no portadoras. Además, se identificaron seis pacientes (5.2%) con una mutación en el gen BRCA2 y sólo una presentó una mutación en el gen BRCA1. Estos resultados y el aumento en la incidencia del cáncer de mama en los últimos a os en Costa Rica deben promover un aumento en medidas de prevención y el establecimiento de métodos de detección más eficientes, que permitan realizar un diagnóstico temprano de la enfermedad. Breast cancer is first in incidence and mortality among Costa Rican women. In 2011 there is a projected 1 071 new cases. We selected 116 patients diagnosed with breast cancer and family history of breast cancer. A detailed family history and epidemiology data was obtained from each patient and a blood sample was processed for DNA extraction. We analyzed the prevalence of risk factors and BRCA1 and BRCA2 mutations. These mutations were detected by different techniques and were confirmed by direct sequencing. Six patients (5.2%) had a mutation, five of which were in the BRCA2 gene and only one in BRCA1. We found that the average age of women who carry a mutation is lower than in non-carrier women. All other risk factors analyzed were not different among carrier and non-carrier women. In addition, these results and the increased incidence of breast cancer in recent years in Costa Rica, should promote an increase in prevention policies and the establishment of efficient detection methods that allow early disease diagnosis.
RAD51C germline mutations in breast and ovarian cancer patients
Mohammad R Akbari, Patricia Tonin, William D Foulkes, Parviz Ghadirian, Marc Tischkowitz, Steven A Narod
Breast Cancer Research , 2010, DOI: 10.1186/bcr2619
Abstract: In order to confirm these findings, we sequenced the nine coding exons of RAD51C in the germline DNA of 454 patients with familial breast/ovarian cancer. The mean age at diagnosis of the breast cancers was 44.7 years (range 21 to 65) and the mean age of diagnosis of the ovarian cancers was 47.9 years (range 23 to 60 years). All patients were previously found to be negative for BRCA1 and BRCA2 mutations. Each proband had at least two affected first- or second-degree relatives. Eighty-five percent of the families contained at least one case of ovarian cancer. One-hundred patients were Jewish, 152 were French-Canadian and 202 were of various other ethnic origins. All subjects provided written informed consent to participate in the study. The study protocol was approved by the ethics committee of the Women's College Research Institute, protocol number 2007-0036-B.We found no deleterious RAD51C mutation among the 454 patients. We found a novel c.146-8A > G splicing variant in three of 100 Jewish breast cancer patients, but this variant was also present in 12 of 190 Jewish controls. In addition, we found one polymorphic missense variant (p.126Ala > Thr or rs61758784) in three patients and one (p.287Thr > Ala or rs28363317) in four patients. Based on the prevalence of mutations in the initial report [2], we expected to identify approximately five families with a deleterious germline RAD51C mutation. It is of interest that the mutations in the German families were all different, and therefore the discrepant results cannot be explained by the presence of RAD51C founder alleles in Germany. Perhaps RAD51C mutations are not as common as the initial report suggests.The authors declare that they have no competing interests.
Prevalence of BRCA1 and BRCA2 mutations in unselected breast cancer patients from Greece
Chrissovaladis Koumpis, Constantine Dimitrakakis, Aris Antsaklis, Robert Royer, Shiyu Zhang, Steven A Narod, Joanne Kotsopoulos
Hereditary Cancer in Clinical Practice , 2011, DOI: 10.1186/1897-4287-9-10
Abstract: To do so, we enrolled 127 unselected women with breast cancer from the Alexandra Hospital in Athens, Greece, a large public hospital in the city. Mutations in BRCA1 and BRCA2 were detected using a combination of techniques and were confirmed by direct sequencing. Two large genomic deletions were sought using mutation-specific assays. A detailed family history of cancer was obtained from each patient.We were able to successfully complete testing on samples from 127 women. Among these, six mutations were identified (four in BRCA1 and two in BRCA2) representing 4.7% of the total or 9.5% of cases diagnosed before age forty. None of the mutation carriers had a family history of breast or ovarian cancer. Three of the four BRCA1 mutations were in exon 20: two were a G5331A mutation and the third was a 3.2 kb deletion. The fourth BRCA1 mutation was the 3819delGTAAA in exon 11. The two BRCA2 mutations were in exon 11 (3782del10 and 4512insT).The G5331A mutation in BRCA1 appears to be a founder mutation in the Greek population.The inheritance of a deleterious mutation in one of the two breast cancer susceptibility genes, BRCA1 and BRCA2, is associated with a high lifetime risk of breast cancer, currently estimated at 80% by the age of 70 [1-3]. Deleterious mutations in both genes also increase the lifetime risks of ovarian cancer and predispose men and women to a range of other malignancies [4-6]. Factors that aid in predicting whether a mutation has been inherited by a woman with breast cancer include the number of breast and/or ovarian cancer patients in the family, the age of diagnosis, her ancestry and various pathological features of the breast cancer [7,8].In North America, Europe, Israel and Australia, women considered to be at high-risk due to a significant family history of breast cancer may undergo molecular testing for mutations in BRCA1 and BRCA2. Genetic screening provides the opportunity for unaffected women who are identified as a carrier of a deleterious mutat
Polymorphic Variation of Genes in the Fibrinolytic System and the Risk of Ovarian Cancer
Yaakov Bentov,Theodore J. Brown,Mohammad R. Akbari,Robert Royer,Harvey Risch,Barry Rosen,John McLaughlin,Ping Sun,Shiyu Zhang,Steven A. Narod,Robert F. Casper
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0005918
Abstract: The etiology of ovarian cancer is largely unknown. One hypothesis is that the inefficient removal of the blood clots and fibrin products which are deposited in the vicinity of the ovary by retrograde menstruation might be associated with an increased risk of ovarian cancer. Several single nucleotide polymorphisms within genes which comprise the fibrinolytic system have been shown to have functional effects on the rate of blood clot degradation. These were considered to be candidate genes in the present study.
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