Cytochrome P450-17alpha Polymorphism and Risk of Breast Cancer PDF Download
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Author: Publisher: ISBN: Category : Languages : en Pages : 5
Book Description
The current study investigates whether polymorphisms in the CYP 17 gene, which plays roles in estrogen biosynthesis, are associated with an altered risk of breast cancer in a population-based sample of women (400 cases and 400 controls) who participated in the Long Island Breast Cancer Study Project (LIBSCP). In addition, we are also exploring whether the effects of reproductive risk factors and exposure to exogenous estrogen are modified by CYP 17 polymorphisms. In the past year, laboratory assays on CYP 17 polymorphisms are being conducted in the Division of Environmental Health Sciences of Columbia University. The polymorphisms are being determined by PCR-RFLP methods with a digestion by appropriate restriction enzymes. To date, assays on 300 cases and 300 controls have been performed. Delays in subject and sample selection in the parent LIBSCP study delayed Task 1, thus delaying the start of laboratory analyses. Therefore, Task 2 will not be completed until the end of September 1999. Entry of laboratory data to computers and merging of laboratory data with questionnaire data (Task 3) are estimated to begin in October 1999. Data analysis, manuscript preparation and report writing (Tasks 4 & 5) will take place in the coming year.
Author: Publisher: ISBN: Category : Languages : en Pages : 5
Book Description
The current study investigates whether polymorphisms in the CYP 17 gene, which plays roles in estrogen biosynthesis, are associated with an altered risk of breast cancer in a population-based sample of women (400 cases and 400 controls) who participated in the Long Island Breast Cancer Study Project (LIBSCP). In addition, we are also exploring whether the effects of reproductive risk factors and exposure to exogenous estrogen are modified by CYP 17 polymorphisms. In the past year, laboratory assays on CYP 17 polymorphisms are being conducted in the Division of Environmental Health Sciences of Columbia University. The polymorphisms are being determined by PCR-RFLP methods with a digestion by appropriate restriction enzymes. To date, assays on 300 cases and 300 controls have been performed. Delays in subject and sample selection in the parent LIBSCP study delayed Task 1, thus delaying the start of laboratory analyses. Therefore, Task 2 will not be completed until the end of September 1999. Entry of laboratory data to computers and merging of laboratory data with questionnaire data (Task 3) are estimated to begin in October 1999. Data analysis, manuscript preparation and report writing (Tasks 4 & 5) will take place in the coming year.
Author: Maria Shuk Mun Lam Publisher: ISBN: Category : Languages : en Pages : 0
Book Description
Bioactivation of environmental procarcinogens and prolonged exposure to 17ß-estradiol and catechol estrogens have been implicated in the etiology of mammary carcinogenesis. Endogenous 17ß-estradiol is oxidized to catechol estrogens by cytochrome P450 CYP1A2 and CYP1B1 enzymes which are transcriptionally regulated by the AH receptor. These enzymes are also involved in the bioactivation of numerous environmental procarcinogens such as benzo['a']pyrene. Consequently, those genetic polymorphisms in 'CYP1A2, CYP1B1' and 'AHR' that result in changes of enzyme or receptor function may affect 17ß-estradiol clearance and metabolic activation of procarcinogens. I genotyped two populations for a total of 7 polymorphisms in the 'AHR, CYP1A2' and ' CYP1B1' genes to examine whether these gene polymorphisms modify estrogen metabolism (Project 1) and breast cancer susceptibility (Project 2). Data of our estrogen metabolism study (Project 1) suggest that the 'AHR ' 554 polymorphism is related to alterations in 17ß-estradiol metabolism. Results of our Quebec French Canadian breast cancer case-control study (Project 2) indicate that the 'AHR' 554, 'CYP1A2*1F, CYP1B1*3' and 'CYP1B1*4' polymorphisms may modify breast cancer susceptibility.
Author: Chi-Chen Hong Publisher: National Library of Canada = Bibliothèque nationale du Canada ISBN: 9780612918108 Category : Languages : en Pages : 494
Book Description
The objective of this thesis was to study the genetic basis of ovarian hormone metabolism and its potential influence on mammographic density levels and other risk factors for breast cancer. Using a cross-sectional design, polymorphisms in 2 genes, P450 c17alpha (CYP17, T27C, A1 and A2 allele, respectively) and catechol-O-methyltransferase (COMT, VAL158MET, COMT*1 and COMT*2 allele, respectively), as well as cytochrome P450 1A2 (CYP1A2) activity were examined in their relationships with mammographic density, sex hormones, the growth hormone-insulin growth factor-I (IGF-1) axis, and anthropometric variables. Each low activity COMT*2 allele was associated with lower levels of percent breast density amongst pre- but not postmenopausal subjects. In premenopausal women the low activity COMT*2 allele was also associated with lower serum levels of IGF-1, higher levels of FSH and progesterone, and with a larger waist-to-hip ratio, body mass index (BMI), and subscapular skinfold. Information was obtained on risk factors, diet, and anthropometric measures. Blood levels of sex hormones, lipids, and growth factors were measured; and, CYP17 and COMT genotypes were determined. In vivo CYP1A2 activity was assessed by measuring caffeine metabolites in urine. Serum and urinary malondialdehyde (MDA), and MDA-deoxyguanosine adducts in DNA were measured. Mammograms were determined using a computer-assisted method. CYP17 genotype was not associated with mammographic density levels. In premenopausal women, the A2 allele was associated with higher levels of dehydroepiandrosterone sulfate, and in postmenopausal women, with higher levels of total estradiol and lower levels of follicle stimulating hormone. Among premenopausal subjects, interactions were observed between CYP17 genotype and endogenous insulin levels as well as various dietary variables. These findings indicate that CYP17 and COMT genotypes, as well as CYP1A2 activity are associated with several risk factors for breast cancer. CYPIA2 activity in post-, but not premenopausal, women was positively associated with breast density levels. In premenopausal women, CYP1A2 activity was associated with serum and urinary MDA levels, age, BMI, smoking status, and levels of sex hormone binding globulin (SHBG), total cholesterol, insulin, triglyceride, and caffeine intake. In postmenopausal subjects, independent associations were observed with smoking status, age at menarche, blood triglycerides, SHBG, and IGF-1 levels.
Author: Paul R. Ortiz de Montellano Publisher: Springer Science & Business Media ISBN: 0387274472 Category : Medical Languages : en Pages : 702
Book Description
Cytochrome P450: Structure, Mechanism, and Biochemistry, third edition is a revision of a review that summarizes the current state of research in the field of drug metabolism. The emphasis is on structure, mechanism, biochemistry, and regulation. Coverage is interdisciplinary, ranging from bioinorganic chemistry of cytochrome P450 to its relevance in human medicine. Each chapter provides an in-depth review of a given topic, but concentrates on advances of the last 10 years.
Author: Regine Goth-Goldstein Publisher: ISBN: Category : Languages : en Pages : 36
Book Description
The proposed study seeks to address the interaction of environmental and genetic factors in the etiology of breast cancer. The cytochrome P450 isozymes CYPlAl and CYP1B1 metabolize environmental and endogenously formed carcinogens in the breast. We are testing the hypothesis that individuals with higher levels of CYP1B1 are at a higher risk for breast cancer because they produce higher amounts of ultimate carcinogen. Genetic polymorphism and expression level of CYP1A1 and CYP1B1 are being determined in a collection of nontumor breast tissue samples from reduction mammoplasties and from mastectomy patients. Frequency of genetic variants and expression is compared in specimens from cancer patients and health controls to establish if breast cancer patients have an increased level of the enzyme. During the last year CYP1B1 and in parallel CYP1A1 expression was determined in an additional 29 specimens using a semiquantitative RT-PCR. All available specimens were analyzed for known genetic polymorphisms in the CYP1A1 and CYP1B1 genes. The difference in variant frequencies between cases and controls was not significant. CYP1B1 transcript levels ranged from 1.5 to 133. CYP1A1 level had an even larger interindividual range. In most specimen CYP1B1 expression was 2-6 fold that of CYP1A1. CYP1B1 expression was significantly higher in the breast cancer group than in the healthy control group.
Author: Shufeng Zhou Publisher: CRC Press ISBN: 131536266X Category : Medical Languages : en Pages : 508
Book Description
Cytochromes are proteins that catalyze electron transfer reactions of well-known metabolic pathways and are classified in various superfamilies. The CYP, or P450, superfamily accounts for 90% of the oxidative metabolism of clinical drugs. One member of this superfamily, P450 2D6 (or CYP2D6), singlehandedly metabolizes about 25% of all medications in the human liver. Cytochrome P450 2D6: Structure, Function, Regulation, and Polymorphism reviews the current knowledge of CYP2D6 as well as the maturing body of evidence indicating its significance to clinical and pharmacological researchers and practitioners. This book focuses on the critical role CYP2D6 plays in the human liver. It examines the genetic, epigenetic, physiological, pathological, and structural factors of the gene that govern the highly variable metabolism of a number of drugs in clinical use. It highlights the impact of the functional roles of CYP2D6 on clinical practice and drug development and also discusses implications for precise medicine, strategies to avoid adverse drug reactions, and paths for future research. Cytochrome P450 2D6 is a unique, valuable book focusing on a single but immensely powerful human gene. It provides the first single source of comprehensive information on CYP2D6 that serves as an important reference for medical, biomedical, pharmaceutical, and nursing researchers, practitioners, and students.
Author: Fritz F. Parl Publisher: IOS Press ISBN: 9780967335544 Category : Breast Languages : en Pages : 280
Book Description
Estrogens have been implicated to play a role in the development of breast cancer. The purpose of this book is to provide a comprehensive analysis of experimental, clinical and epidemiological evidence in support of the carcinogenicity of estrogens.
Author: Andrea Dunaif Publisher: Springer Science & Business Media ISBN: 1597451088 Category : Medical Languages : en Pages : 361
Book Description
This volume includes the latest diagnostic criteria for PCOS and comprises the most up-to-date information about the genetic features and pathogenesis of PCOS. It critically reviews the methodological approaches and the evidence for various PCOS susceptibility genes. The book also discusses additional familial phenotypes of PCOS and their potential genetic basis. All four editors of this title are extremely prominent in the field of PCOS.
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Author: Maria Shuk Mun Lam![Influence of Genetic Polymorphisms in P450 C17α (T27C), Catechol-O-methyltransferase (VAL158MET), and Activity Level of Cytochrome P450 1A2 on Mammographic Density Levels and Other Risk Factors for Breast Cancer [microform] PDF](https://books.google.com/books/content/images/frontcover/2kHQygAACAAJ?fife=w80-h100)
Author: Chi-Chen Hong
Author: Paul R. Ortiz de Montellano
Author: Regine Goth-Goldstein
Author: Shufeng Zhou
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Author: Fritz F. Parl
Author: Andrea Dunaif
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