Author: Mary-Claire King
Publisher:
ISBN:
Category :
Languages : en
Pages : 22
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Book Description
Women with inherited mutations in BRCAl or BRCA2 have significantly elevated risks of breast cancer. However, not all women with inherited BRCAl or BRCA2 mutations develop breast or ovarian cancer, and among those who do, ages at cancer onset vary widely even within the same family. If a woman with a BRCAl or BRCA2 mutation remains free of breast cancer for many years, it is possible that her status is due to chance, to modifying genes segregating in some families, or to environmental factors that influence risk. In this project, we evaluate environmental and lifestyle factors that could influence the impact of mutations in BRCA I and BRCA2 on disease risk. It is possible that such co-factors identified among genetically predisposed women may be generalized to women who have not inherited predisposition to breast or ovarian cancer, because clinically and biologically, inherited cancer is virtually indistinguishable from its far more common, non-inherited counterpart.
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 19
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Book Description
This project aims to identify potentially preventable environmental influences on breast and ovarian cancer by focusing on a population of women with genetically inherited predisposition to the disease. This is an extension of our ongoing research into the genetics of breast and ovarian cancer among Jewish women in the New York City area. The IDEA project centered on female relatives of breast cancer patients with confirmed mutations in BRCAl or BRCA2. Each relative provided a blood sample for mutation testing and completed an extensive questionnaire addressing epidemiologic factors in breast cancer risk. Among participants, inherited mutations in BRCAl and BRCA2 were more frequent in women with a younger breast cancer diagnosis and in women with a breast and/or ovarian cancer family history. Breast cancer risks increased over time among women with mutations, suggesting the influence of environmental factors. The experiences and exposures of women with mutations who did and did not develop breast or ovarian cancer were compared to identify factors that ameliorate or exacerbate risk in this high-risk group. These risk factors may be generalized to women without inherited vulnerability to breast or ovarian cancer, as inherited cancer is virtually indistinguishable, clinically and biologically, from its non inherited counterpart.
Author: Barbara T. Zimmerman
Publisher: Univ. Press of Mississippi
ISBN: 9781578065783
Category : Health & Fitness
Languages : en
Pages : 142
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Book Description
Health & Sickness -- Consumer Health This book by a scientist whose background is in cellular and molecular biology examines the fearsome disease that strikes one in eight women in the United States. Although women are more likely to die of heart disease or of lung cancer, a diagnosis of breast cancer is the medical pronouncement that a woman is most likely to fear. It kills more than 40,000 Americans annually. Why are some women more vulnerable than others? The interplay between genetics and environment is suspected. Thus this book for general readers will help them understand the genetic bases of both sporadic and inherited breast cancers. Although only five to ten percent of breast cancer patients have inherited mutations in these genes, all women need to understand the genetic implications of the disease. In clear, concise language Barbara T. Zimmerman guides the reader through the complexities, discussing in detail the genes that are known to increase susceptibility and the ways they are passed on. Examining the general biology of breast cancer, Zimmerman describes how sporadic and inherited forms of the disease arise and how the location of the tumors can affect the body. She discusses genetic mutations and their roles in the development of tumors and tells how these potentially cancer-inducing genes were discovered. Covered too are the issues of risk, prevention, screening, diagnosis, therapy, and genetic testing and counseling. Zimmerman concludes with a comprehensive analysis of current research and with an emphasis on how a woman's understanding of inherited breast cancer can help doctors seeking to design better methods for prevention and therapy. A useful list of resources for further information about the genetic causes of breast cancer is included. Barbara T. Zimmerman did her graduate work in experimental pathology and her post-doctoral research in the cellular and molecular processes of disease. Widely published, she is the manager of the Denver-based firm Biomedical Communication and Consulting.
Author: Jorunn E. Eyfjord
Publisher:
ISBN:
Category :
Languages : en
Pages : 20
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Book Description
One mutation in each BRCA gene, a BRCA2 founder mutation and a rare BRCAl mutation account for most familial breast cancer in a well defined population. Our previous studies show that the penetrance of the BRCA2 mutation varies greatly, suggesting the involvement of modifying factors, genetic and/or environmental. The study group consists of all women in Iceland who have had breast cancer and are alive at the time of study, their female relatives and age matched controls, estimated 5000 women. Hypotheses tested are that environmental risk factors and genetic variation in metabolic enzymes affect, 1. Penetrance of BRCA mutations 2. Breast cancer risk in the population Hypothesis 1. is studied in women with breast cancer who have a BRCA mutation and mutation carrier relatives without breast cancer. Comparison group are women with breast cancer without BRCA mutations and unaffected mutation negative relatives. Risk factors investigated: Reproductive factors, ionizing radiation, physical exercise, alcohol use, smoking, height and weight. The enzymes investigated affect levels of sex hormones and formation of carcinogenic substances. 2. is studied in 1200 women with breast cancer, representative for breast cancer patients in the population, and 1200 age-matched controls without breast cancer, representative for women without breast cancer.
Author: Institute of Medicine
Publisher: National Academies Press
ISBN: 0309220696
Category : Medical
Languages : en
Pages : 468
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Book Description
Breast cancer remains the most common invasive cancer among women. The primary patients of breast cancer are adult women who are approaching or have reached menopause; 90 percent of new cases in U.S. women in 2009 were diagnosed at age 45 or older. Growing knowledge of the complexity of breast cancer stimulated a transition in breast cancer research toward elucidating how external factors may influence the etiology of breast cancer. Breast Cancer and the Environment reviews the current evidence on a selection of environmental risk factors for breast cancer, considers gene-environment interactions in breast cancer, and explores evidence-based actions that might reduce the risk of breast cancer. The book also recommends further integrative research into the elements of the biology of breast development and carcinogenesis, including the influence of exposure to a variety of environmental factors during potential windows of susceptibility during the full life course, potential interventions to reduce risk, and better tools for assessing the carcinogenicity of environmental factors. For a limited set of risk factors, evidence suggests that action can be taken in ways that may reduce risk for breast cancer for many women: avoiding unnecessary medical radiation throughout life, avoiding the use of some forms of postmenopausal hormone therapy, avoiding smoking, limiting alcohol consumption, increasing physical activity, and minimizing weight gain. Breast Cancer and the Environment sets a direction and a focus for future research efforts. The book will be of special interest to medical researchers, patient advocacy groups, and public health professionals.
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: Yosr Hamdi
Publisher:
ISBN:
Category :
Languages : en
Pages : 495
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Book Description
Breast cancer is the most common malignancy in women. A set of environmental and genetic factors are involved in this complex disease. This project focused on the genetic components of breast cancer susceptibility and breast cancer risk modification in BRCA1 and BRCA2 mutation carriers. Currently, about half of the inherited susceptibility to breast cancer can be imputed to a combination of high-, intermediate-, and low-risk alleles. Thus, many as yet unknown susceptibility loci remain to be identified. Moreover, recent studies have provided evidence for the involvement of genetic risk factors that might considerably modify the risk of developing breast cancer in BRCA1 and BRCA2 mutation carriers. Furthermore, genome-wide association studies have shown that several genetic variants within non-coding gene regions are associated with breast cancer risk. In this project, we focused on regulatory gene variants and their association with breast cancer risk. The project was divided in two parts. In the first section, we evaluated the direct association between single-nucleotide polymorphisms associated with differential allelic expression and breast cancer risk in order to identify new loci of breast cancer susceptibility. In the second part, we evaluated the functional impact on gene expression of variants identified within the promoter regions of selected candidate genes and then, characterize the functional impact of these variants. In summary, the first part of this project has led to the identification of a new low-penetrance locus associated with breast cancer risk on the 4q21 locus (rs11099601; odds ratio=1.05, p= 6.4 x 10-6), and two new modifiers of breast cancer risk in BRCA1 mutations carriers (11q22.3 locus and the wild type allele of BRCA1). The second part of the project allowed us to describe new functional variants within the promoters of the selected breast cancer gene candidates. Other association studies in larger cohorts and further functional analysis will be required to confirm these results, which will allow their inclusion in breast cancer risk prediction tools and thus ensure a more accurate estimation of breast cancer risk.
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: Joanne Kotsopoulos
Publisher:
ISBN: 9780494280560
Category :
Languages : en
Pages : 554
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Book Description
The lifetime risk of developing breast cancer due to an inherited mutation in the breast cancer susceptibility gene, BRCA1, is estimated to be 80%. Management options include screening for early detection or primary prevention with prophylactic surgery or drug therapy. The limited uptake of these options illustrates the need to explore alternative preventive strategies that include dietary or lifestyle changes. Prospective trials using breast cancer as the principle endpoint when evaluating the protective role of nutrients is not feasible in this high-risk population. BRCA1 helps maintain genomic integrity through the participation in antioxidant responses and the repair of double-stranded DNA breaks. Thus, the overall goal of this dissertation was to exploit the known functions of the BRCA1 protein to elucidate a biomarker that could distinguish between BRCA1 mutation carriers and non-carriers, and furthermore, to correlate these markers of susceptibility with levels of dietary factors, more specifically, coffee, selenium and lycopene. These nutrients were selected based on the hypothesis that dietary changes that decrease oxidative damage (possibly linked to estrogen exposure) or enhance the DNA damage repair pathways, may modulate breast cancer risk. We evaluated the ability of a panel of biomarkers that reflected both DNA repair capacity and oxidative status to predict the presence of a BRCA1 mutation, and found no difference. Coffee consumption was associated with a significant reduction in breast cancer risk among mutation carriers. Among women with a BRCA1 mutation, toenail selenium was associated with significantly lower levels of chromosomal damage as assessed by the micronucleus test. An increase in oxidative damage to proteins, and to a lesser extent, lipids, with increasing dietary lycopene intake was limited to mutation carriers. These pro-oxidant effects require confirmation. Collectively, these findings translate into the prevention of BRCA1-associated breast cancer through interventions with selenium and other factors that may minimize chromosomal damage. The prospect of unique diets to prevent hereditary breast cancer may therefore be possible by protecting genomic stability due to an inherited BRCA1 mutation.
Author:
Publisher:
ISBN:
Category : Breast
Languages : en
Pages : 88
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Book Description
