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Author: Tara Mee-Stacy Short
Publisher:
ISBN: 9781124020549
Category :
Languages : en
Pages : 76
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Book Description
Many researchers are investigating modifiers that could cause the variation in cancer risks that are observed in BRCA1 and BRCA2 mutation carriers. This thesis was an exploratory study to investigate whether there were differences in cancer risks in female offspring depending on whether the BRCA1 or BRCA2 mutation was inherited from the mother or the father. Research shows that BRCA1 affects more molecular pathways than BRCA2. We hypothesized that BRCA1 mutation carriers would be more likely to show significant evidence of a parental origin effect. We hypothesized that due to a female's haplo-insufficiency, her offspring would have an altered in utero exposure that would increase the cancer risk associated with her offspring's inherited BRCA1 mutation. 300 females and 184 females with BRCA1 and BRCA2 mutations, respectively, and an identifiable parent of origin were analyzed using Pearson chi-square, two-sample t-tests and Kaplan-Meier survival curves. The majority of cancers were breast cancers. No parental origin effect was observed in BRCA1 mutation carriers (p-values from 0.414 to 0.768). For BRCA2 mutation carriers, the range of hazard ratios was 1.32 [95% Confidence Interval (CI) of 0.85-2.07] for breast cancer only, 1.42 (95% CI of 0.94-2.15) for breast or ovarian cancer, 1.43 (95% CI of 0.96-2.13) for all cancers, and 2.31 (95% CI of 0.74-7.23) for ovarian cancer only in our larger study sample, showing that inheriting the mutation from their fathers increases women's cancer risks. Additional studies with larger sample sizes and adjusting for other confounders, such as preventative cancer treatments, are needed.
Author: Tara Mee-Stacy Short
Publisher:
ISBN: 9781124020549
Category :
Languages : en
Pages : 76
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Book Description
Many researchers are investigating modifiers that could cause the variation in cancer risks that are observed in BRCA1 and BRCA2 mutation carriers. This thesis was an exploratory study to investigate whether there were differences in cancer risks in female offspring depending on whether the BRCA1 or BRCA2 mutation was inherited from the mother or the father. Research shows that BRCA1 affects more molecular pathways than BRCA2. We hypothesized that BRCA1 mutation carriers would be more likely to show significant evidence of a parental origin effect. We hypothesized that due to a female's haplo-insufficiency, her offspring would have an altered in utero exposure that would increase the cancer risk associated with her offspring's inherited BRCA1 mutation. 300 females and 184 females with BRCA1 and BRCA2 mutations, respectively, and an identifiable parent of origin were analyzed using Pearson chi-square, two-sample t-tests and Kaplan-Meier survival curves. The majority of cancers were breast cancers. No parental origin effect was observed in BRCA1 mutation carriers (p-values from 0.414 to 0.768). For BRCA2 mutation carriers, the range of hazard ratios was 1.32 [95% Confidence Interval (CI) of 0.85-2.07] for breast cancer only, 1.42 (95% CI of 0.94-2.15) for breast or ovarian cancer, 1.43 (95% CI of 0.96-2.13) for all cancers, and 2.31 (95% CI of 0.74-7.23) for ovarian cancer only in our larger study sample, showing that inheriting the mutation from their fathers increases women's cancer risks. Additional studies with larger sample sizes and adjusting for other confounders, such as preventative cancer treatments, are needed.
Author:
Publisher:
ISBN:
Category : Breast
Languages : en
Pages : 88
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Book Description
Author: Albert Altchek
Publisher: Elsevier
ISBN: 008049451X
Category : Medical
Languages : en
Pages : 595
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Book Description
This updated second edition of Diagnosis and Management of Ovarian Disorders provides thorough, yet succinct insight into the ever-changing realm of ovarian disorders. It presents a novel multidisciplinary approach to the subject as described by clinicians, surgeons, pathologists, basic scientists and related medical researchers. Topics covered include reproductive technology, early diagnosis of ovarian cancer, and management of menopause among others. The breadth of information provided by this book will appeal to clinicians and researchers involved in the study and treatment of ovarian disorders. KEY FEATURES* Includes updated information on early diagnosis of ovarian cancer* Reviews new diagnostic techniques for ovarian disorders* Discusses latest information on reproductive technology* Presents translational treatment linking laboratory research with clinical medicine
Author:
Publisher:
ISBN: 9780199558391
Category : Cancer
Languages : en
Pages : 93
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Book Description
Author: U.S. Department of Health and Human Services
Publisher: Createspace Independent Publishing Platform
ISBN: 9781495306136
Category : Medical
Languages : en
Pages : 368
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Book Description
This systematic review is an update of the evidence for the U.S. Preventive Services Task Force (USPSTF) on the effectiveness and adverse effects of risk assessment, genetic counseling, and genetic testing for breast cancer susceptibility gene (BRCA)–related cancer in women who do not have cancer but are potentially at increased risk. Its purpose is to evaluate and summarize evidence addressing specific key questions important to the USPSTF as it considers new recommendations for primary care practice. In 2005, based on results of a previous review, the USPSTF recommended against routine referral for genetic counseling or routine BRCA testing for women whose family histories are not associated with increased risks for deleterious mutations in breast cancer susceptibility gene 1 (BRCA1) or breast cancer susceptibility gene 2 (BRCA2) (D recommendation). The USPSTF also recommended that women whose family histories are associated with increased risks for mutations in the BRCA1 or BRCA2 genes be referred for genetic counseling and evaluation for BRCA testing (B recommendation). The USPSTF concluded that the potential harms of routine referral for genetic counseling or BRCA mutation testing in women without family history risk outweigh the benefits, and that the benefits of referring women with family history risk to suitably trained health care providers outweigh the harms. Benefits included improved accuracy of risk assessment and pretest probability for testing and improved patient knowledge, risk perception, and psychological and health outcomes. Potential harms included inaccurate risk assessment; inappropriate testing; misinterpretation of test results; and ethical, legal, and social implications; among others. The 2005 USPSTF recommendation was intended for the primary prevention of cancer and applied to women without previous diagnoses of breast or ovarian cancer, consistent with the USPSTF scope of preventive care for the general population. Recommendations for men and women with cancer were not included. The 2005 USPSTF recommendation is included in the Affordable Care Act for covered preventive services, and provided the basis for a Healthy People 2020 objective to increase the proportion of women with family histories of breast or ovarian cancer who receive genetic counseling. The previous systematic review identified several research limitations and evidence gaps. The review concluded that a primary care approach to genetic risk assessment and BRCA mutation testing had not been evaluated, and evidence was lacking to determine the benefits and harms of this approach for women without cancer. Risk assessment, genetic counseling, and mutation testing did not cause adverse psychological outcomes, and counseling improved distress and risk perception in the highly-selected populations studied. Studies of intensive cancer screening approaches, such as earlier and more frequent mammography, were inconclusive. Trials of risk-reducing medications, such as tamoxifen and raloxifene, reported reduced breast cancer incidence in women with varying baseline levels of risk compared with placebo, but also increased adverse effects. Observational studies of risk-reducing mastectomy and salpingooophorectomy reported reduced breast and ovarian cancer outcomes in women who were mutation carriers.
Author: Wei Liu
Publisher: Open Dissertation Press
ISBN: 9781374665835
Category :
Languages : en
Pages :
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Book Description
This dissertation, "Genetic Analysis of the BRCA1 and BRCA2 Genes in Breast Cancer of Hong Kong Chinese" by Wei, Liu, 劉蔚, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled Genetic Analysis of the BRCA1 and BRCA2 Genes in Breast Cancer of Hong Kong Chinese Submitted by LIU WEI for the degree of Doctor of Philosophy at the University of Hong Kong December 2007 BRCA1 and BRCA2 genes are important breast cancer susceptibility genes. In order to understand the role of common genetic variation and aberrant genetic alteration of BRCA genes in breast cancer in Hong Kong Chinese, we performed genetic association study of polymorphisms, screened for recurrent mutations and rearrangements in Hong Kong breast cancer patients. Previous studies on polymorphisms of BRCA genes were performed mainly on the Caucasian population, but their findings have been controversial. We hypothesized that promoter polymorphism may alter the binding site of transcription factors thus affect transcriptional activity, and coding region single nucleotide polymorphisms (SNPs) can alter the conformation of functional domain and thus affect susceptibility to disease. Non-synonymous SNPs of BRCA1 and BRCA2 were selected from dbSNP database and literature. Promoter polymorphisms were identified by direct sequencing for this study. SNPs with minor allele frequency >5% were selected for risk association analysis. Significant association was found for the genotypes and alleles of BRCA1 -969C/T SNP in 380 breast cancer cases and 390 age matched controls in Hong Kong Chinese women, but absent for other BRCA1 and BRCA2 polymorphisms. Individuals carrying -969CT or TT genotype had a reduced risk for breast cancer (OR=0.64; 95%CI=0.47-0.88), which was more evident among women aged >= 45 years without family history of breast cancer (OR=0.51, 95%CI=0.32-0.81) in Hong Kong. This association was replicated in 1109 cases and 1185 controls recruited from a population-based study of Shanghai Chinese, with adjusted OR=0.85 (95%CI=0.71-1.00) for all women and 0.79 (95%CI=0.63-0.99) for women aged >= 45 years without a family history of breast cancer. Combined analysis of the two populations showed T-carriers were with lower risk (combined OR=0.80, 95%CI=0.69-0.93). Promoter activity analysis and electrophoretic mobility shift (EMSA) assays confirmed that promoter constructs containing the - 969T allele had 1.7 to 2.1 -fold increased activity and provided stronger binding with nuclear protein, compared with the -969C allele. We also screened for recurrent mutations as several novel BRCA mutations have been identified in Hong Kong Chinese, some of which appear unique to the population. Three mutations, the 589delCT and 4491C>T mutation in BRCA1 and 3337C>T mutation in BRCA2 were identified in three different and unrelated patients. Haplotype analysis demonstrated that these three mutations have recurred with founder effect. In addition to point mutations, large deletion and amplification of BRCA1 and BRCA2 genes have been identified as aberrant genetic changes in high risk breast cancer patients. The multiplex ligation-dependent probe amplification (MLPA) method was applied to screen for these alterations on 46 high risk breast cancer patients. No rearrangements were however identified. Our results demonstrated the -969C/T BRCA1 promoter polymorphism can affect breast cancer susceptibility by enhancement of BRCA1 promoter activity and up- regulation of gene expression. Three founder BRCA mutations were identified and it should have important implications for genetic test
Author: Elizabeth Nilan
Publisher:
ISBN:
Category : Breast
Languages : en
Pages : 116
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Book Description
246,660 women every year are diagnosed with breast cancer ("What Are the Key Statistics"). That is a one in eight lifetime risk for every woman. One in every 500 women will test positive for the BRCA genetic mutation in their lifetime, making it very rare ("BRCA Gene Mutations"). Testing positive means that genetically, a person has heightened cancer risks. ¶ The decision to test, act, or not act on results is a complex decision-making process that is influenced by societal norms, but should be a personal decision that is right for the individual woman herself. This study was carried out through interviews that focused on the experiences of BRCA+ women and how patriarchal society reacted to these women undergoing genetic testing, and testing positive for the BRCA1 or BRCA2 genetic mutation. This research focused on finding the point these women became empowered through their decision-making process, from deciding to go through with the genetic testing, to acting on their positive results.
Author: National Academies of Sciences, Engineering, and Medicine
Publisher: National Academies Press
ISBN: 0309380499
Category : Medical
Languages : en
Pages : 397
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Book Description
In an era of promising advances in cancer research, there are considerable and even alarming gaps in the fundamental knowledge and understanding of ovarian cancer. Researchers now know that ovarian cancer is not a single disease-several distinct subtypes exist with different origins, risk factors, genetic mutations, biological behaviors, and prognoses. However, persistent questions have impeded progress toward improving the prevention, early detection, treatment, and management of ovarian cancers. Failure to significantly improve morbidity and mortality during the past several decades is likely due to several factors, including the lack of research being performed by specific disease subtype, lack of definitive knowledge of the cell of origin and disease progression, and incomplete understanding of genetic and non-genetic risk factors. Ovarian Cancers examines the state of the science in ovarian cancer research, identifies key gaps in the evidence base and the challenges to addressing those gaps, considers opportunities for advancing ovarian cancer research, and examines avenues for translation and dissemination of new findings and communication of new information to patients and others. This study makes recommendations for public- and private-sector efforts that could facilitate progress in reducing the incidence of morbidity and mortality from ovarian cancers.
Author: Eric J. Bieber
Publisher: Cambridge University Press
ISBN: 1107040396
Category : Medical
Languages : en
Pages : 1127
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Book Description
Written with the busy practice in mind, this book delivers clinically focused, evidence-based gynecology guidance in a quick-reference format. It explores etiology, screening, tests, diagnosis, and treatment for a full range of gynecologic health issues. The coverage includes the full range of gynecologic malignancies, reproductive endocrinology and infertility, infectious diseases, urogynecologic problems, gynecologic concerns in children and adolescents, and surgical interventions including minimally invasive surgical procedures. Information is easy to find and absorb owing to the extensive use of full-color diagrams, algorithms, and illustrations. The new edition has been expanded to include aspects of gynecology important in international and resource-poor settings.
Author: Alison Fiander
Publisher: Cambridge University Press
ISBN: 1107667135
Category : Education
Languages : en
Pages : 557
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Book Description
A fully updated and illustrated handbook providing comprehensive coverage of all curriculum areas covered by the MRCOG Part 1 examination.
