The Experts below are selected from a list of 188421 Experts worldwide ranked by ideXlab platform
Ercole L Cavalieri - One of the best experts on this subject based on the ideXlab platform.
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unbalanced Estrogen metabolism in thyroid cancer
International Journal of Cancer, 2013Co-Authors: Muhammad Zahid, Ercole L Cavalieri, Eleanor G. Rogan, Whitney S Goldner, Cheryl L BeselerAbstract:Well-differentiated thyroid cancer most frequently occurs in premenopausal women. Greater exposure to Estrogens may be a risk factor for thyroid cancer. To investigate the role of Estrogens in thyroid cancer, a spot urine sample was obtained from 40 women with thyroid cancer and 40 age-matched controls. Thirty-eight Estrogen metabolites, conjugates and DNA adducts were analyzed by using ultraperformance liquid chromatography/tandem mass spectrometry and the ratio of adducts to metabolites and conjugates was calculated for each sample. The ratio of depurinating Estrogen-DNA adducts to Estrogen metabolites and conjugates significantly differed between cases and controls (p < 0.0001), demonstrating high specificity and sensitivity. These findings indicate that Estrogen metabolism is unbalanced in thyroid cancer and suggest that formation of Estrogen-DNA adducts might play a role in the initiation of thyroid cancer.
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Estrogens as endogenous genotoxic agents dna adducts and mutations
Journal of The National Cancer Institute Monographs, 2000Co-Authors: Ercole L Cavalieri, Eleanor G. Rogan, Joachim G. Liehr, Krystyna Frenkel, Deodutta RoyAbstract:Estrogens induce tumors in laboratory animals and have been associated with breast and uterine cancers in humans. In relation to the role of Estrogens in the induction of cancer, we examine formation of DNA adducts by reactive electrophilic Estrogen metabolites, formation of reactive oxygen species by Estrogens and the resulting indirect DNA damage by these oxidants, and, finally, genomic and gene mutations induced by Estrogens. Quinone intermediates derived by oxidation of the catechol Estrogens 4-hydroxyestradiol or 4-hydroxyestrone may react with purine bases of DNA to form depurinating adducts that generate highly mutagenic apurinic sites. In contrast, quinones of 2-hydroxylated Estrogens produce less harmful, stable DNA adducts. The catechol Estrogen metabolites may also generate potentially mutagenic oxygen radicals by metabolic redox cycling or other mechanisms. Several types of indirect DNA damage are caused by Estrogen-induced oxidants, such as oxidized DNA bases, DNA strand breakage, and adduct formation by reactive aldehydes derived from lipid hydroperoxides. Estradiol and the synthetic Estrogen diethylstilbestrol also induce numerical and structural chromosomal aberrations and several types of gene mutations in cells in culture and in vivo. In conclusion, Estrogens, including the natural hormones estradiol and estrone, must be considered genotoxic carcinogens on the basis of the evidence outlined in this chapter.
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chapter 4 Estrogens as endogenous genotoxic agents dna adducts and mutations
Journal of The National Cancer Institute Monographs, 2000Co-Authors: Ercole L Cavalieri, Eleanor G. Rogan, Joachim G. Liehr, Krystyna Frenkel, Deodutta RoyAbstract:Estrogens induce tumors in laboratory animals and have been associated with breast and uterine cancers in humans. In relation to the role of Estrogens in the induction of cancer, we examine formation of DNA adducts by reactive electrophilic Estrogen metabolites, formation of reactive oxygen species by Estrogens and the resulting indirect DNA damage by these oxidants, and, finally, genomic and gene mutations induced by Estrogens. Quinone intermediates derived by oxidation of the catechol Estrogens 4-hydroxyestradiol or 4-hydroxyestrone may react with purine bases of DNA to form depurinating adducts that generate highly mutagenic apurinic sites. In contrast, quinones of 2-hydroxylated Estrogens produce less harmful, stable DNA adducts. The catechol Estrogen metabolites may also generate potentially mutagenic oxygen radicals by metabolic redox cycling or other mechanisms. Several types of indirect DNA damage are caused by Estrogen-induced oxidants, such as oxidized DNA bases, DNA strand breakage, and adduct formation by reactive aldehydes derived from lipid hydroperoxides. Estradiol and the synthetic Estrogen diethylstilbestrol also induce numerical and structural chromosomal aberrations and several types of gene mutations in cells in culture and in vivo .I n conclusion, Estrogens, including the natural hormones estradiol and estrone, must be considered genotoxic carcinogens on the basis of the evidence outlined in this chapter. [J Natl Cancer Inst Monogr 2000;27:75–93]
Deodutta Roy - One of the best experts on this subject based on the ideXlab platform.
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Estrogens as endogenous genotoxic agents dna adducts and mutations
Journal of The National Cancer Institute Monographs, 2000Co-Authors: Ercole L Cavalieri, Eleanor G. Rogan, Joachim G. Liehr, Krystyna Frenkel, Deodutta RoyAbstract:Estrogens induce tumors in laboratory animals and have been associated with breast and uterine cancers in humans. In relation to the role of Estrogens in the induction of cancer, we examine formation of DNA adducts by reactive electrophilic Estrogen metabolites, formation of reactive oxygen species by Estrogens and the resulting indirect DNA damage by these oxidants, and, finally, genomic and gene mutations induced by Estrogens. Quinone intermediates derived by oxidation of the catechol Estrogens 4-hydroxyestradiol or 4-hydroxyestrone may react with purine bases of DNA to form depurinating adducts that generate highly mutagenic apurinic sites. In contrast, quinones of 2-hydroxylated Estrogens produce less harmful, stable DNA adducts. The catechol Estrogen metabolites may also generate potentially mutagenic oxygen radicals by metabolic redox cycling or other mechanisms. Several types of indirect DNA damage are caused by Estrogen-induced oxidants, such as oxidized DNA bases, DNA strand breakage, and adduct formation by reactive aldehydes derived from lipid hydroperoxides. Estradiol and the synthetic Estrogen diethylstilbestrol also induce numerical and structural chromosomal aberrations and several types of gene mutations in cells in culture and in vivo. In conclusion, Estrogens, including the natural hormones estradiol and estrone, must be considered genotoxic carcinogens on the basis of the evidence outlined in this chapter.
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chapter 4 Estrogens as endogenous genotoxic agents dna adducts and mutations
Journal of The National Cancer Institute Monographs, 2000Co-Authors: Ercole L Cavalieri, Eleanor G. Rogan, Joachim G. Liehr, Krystyna Frenkel, Deodutta RoyAbstract:Estrogens induce tumors in laboratory animals and have been associated with breast and uterine cancers in humans. In relation to the role of Estrogens in the induction of cancer, we examine formation of DNA adducts by reactive electrophilic Estrogen metabolites, formation of reactive oxygen species by Estrogens and the resulting indirect DNA damage by these oxidants, and, finally, genomic and gene mutations induced by Estrogens. Quinone intermediates derived by oxidation of the catechol Estrogens 4-hydroxyestradiol or 4-hydroxyestrone may react with purine bases of DNA to form depurinating adducts that generate highly mutagenic apurinic sites. In contrast, quinones of 2-hydroxylated Estrogens produce less harmful, stable DNA adducts. The catechol Estrogen metabolites may also generate potentially mutagenic oxygen radicals by metabolic redox cycling or other mechanisms. Several types of indirect DNA damage are caused by Estrogen-induced oxidants, such as oxidized DNA bases, DNA strand breakage, and adduct formation by reactive aldehydes derived from lipid hydroperoxides. Estradiol and the synthetic Estrogen diethylstilbestrol also induce numerical and structural chromosomal aberrations and several types of gene mutations in cells in culture and in vivo .I n conclusion, Estrogens, including the natural hormones estradiol and estrone, must be considered genotoxic carcinogens on the basis of the evidence outlined in this chapter. [J Natl Cancer Inst Monogr 2000;27:75–93]
Louise A Brinton - One of the best experts on this subject based on the ideXlab platform.
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circulating Estrogens and postmenopausal ovarian and endometrial cancer risk among current hormone users in the women s health initiative observational study
Cancer Causes & Control, 2019Co-Authors: Britton Trabert, Sally B Coburn, Roni T Falk, Joann E Manson, Louise A Brinton, Margery Gass, Lewis H Kuller, Thomas E Rohan, Ruth M PfeifferAbstract:Menopausal hormone therapy (MHT) use induces alterations in circulating Estrogens/Estrogen metabolites, which may contribute to the altered risk of reproductive tract cancers among current users. Thus, the current study assessed associations between circulating Estrogens/Estrogen metabolites and ovarian and endometrial cancer risk among MHT users. We conducted a nested case–control study among postmenopausal women using MHT at baseline in the Women’s Health Initiative Observational Study (179 ovarian cancers, 396 controls; 230 endometrial cancers, 253 controls). Multivariable logistic regression was utilized to estimate odds ratios and 95% confidence intervals overall and by subtype. Estrogen/Estrogen metabolite levels were not associated with overall or serous ovarian cancer risk, examined separately. However, unconjugated estradiol was positively associated with non-serous ovarian cancer risk [quintile 5 vs. quintile 1: 3.01 (1.17–7.73); p-trend = 0.03; p-het < 0.01]. Endometrial cancer risk was unrelated to Estrogen/Estrogen metabolite levels among women who took combined Estrogen/progestin therapy (EPT). These findings provide novel evidence that may support a heterogeneous hormonal etiology across ovarian cancer subtypes. Circulating Estrogens did not influence endometrial cancer risk among women with EPT-induced high-Estrogen levels. Larger studies are needed to delineate the relationship between ovarian/endometrial cancer subtypes and Estrogen levels in the context of MHT use.
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anthropometric measures and serum Estrogen metabolism in postmenopausal women the women s health initiative observational study
Breast Cancer Research, 2017Co-Authors: Sally B Coburn, Charles E Matthews, Roni T Falk, Louise A Brinton, Ruth M Pfeiffer, Joshua N Sampson, Erin S Leblanc, Jean Wactawskiwende, Nicolas Wentzensen, Garnet L AndersonAbstract:Several anthropometric measures have been associated with hormone-related cancers. However, it is unknown whether Estrogen metabolism plays an important role in these relationships. We examined whether measured current body mass index (BMI), waist-to-hip ratio (WHR), height, and self-reported BMI at age 18 years were associated with serum Estrogens/Estrogen metabolites using baseline, cross-sectional data from 1835 postmenopausal women enrolled in the Women’s Health Initiative Observational Study. Fifteen Estrogens/Estrogen metabolites were quantified using liquid chromatography-tandem mass spectrometry. Geometric means (GMs) of Estrogens/Estrogen metabolites (in picomoles per liter) were estimated using inverse probability weighted linear regression, adjusting for potential confounders and stratified on menopausal hormone therapy (MHT) use. Among never or former MHT users, current BMI (≥30 vs. <25 kg/m2) was positively associated with parent Estrogens (multivariable adjusted GM 432 vs. 239 pmol/L for estrone, 74 vs. 46 pmol/L for estradiol; p-trend < 0.001 for both) and all of the 2-, 4-, and 16-pathway Estrogen metabolites evaluated (all p-trend ≤ 0.02). After additional adjustment for estradiol, unconjugated methylated 2-catechols were inversely associated (e.g., 2-methoxyestrone multivariable GM 9.3 vs. 12.0 pmol/L; p-trend < 0.001). Among current MHT users, current BMI was not associated with parent Estrogens but was inversely associated with methylated catechols (e.g., 2-methoxyestrone multivariable GM 216 vs. 280 pmol/L; p-trend = 0.008). Similar patterns of association were found with WHR; however, the associations were not independent of BMI. Height and BMI at age 18 years were not associated with postmenopausal Estrogens/Estrogen metabolite levels. Our data suggest that postmenopausal BMI is associated with increased circulating levels of parent Estrogens and reduced methylation of catechol Estrogen metabolites, the Estrogen metabolism patterns that have previously been associated with higher breast cancer risk.
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Anthropometric measures and serum Estrogen metabolism in postmenopausal women: the Women’s Health Initiative Observational Study
Breast Cancer Research, 2017Co-Authors: Sally B Coburn, Charles E Matthews, Jean Wactawski-wende, Roni T Falk, Louise A Brinton, Ruth M Pfeiffer, Erin S Leblanc, Nicolas Wentzensen, Joshua Sampson, Garnet L AndersonAbstract:Background Several anthropometric measures have been associated with hormone-related cancers. However, it is unknown whether Estrogen metabolism plays an important role in these relationships. We examined whether measured current body mass index (BMI), waist-to-hip ratio (WHR), height, and self-reported BMI at age 18 years were associated with serum Estrogens/Estrogen metabolites using baseline, cross-sectional data from 1835 postmenopausal women enrolled in the Women’s Health Initiative Observational Study. Methods Fifteen Estrogens/Estrogen metabolites were quantified using liquid chromatography-tandem mass spectrometry. Geometric means (GMs) of Estrogens/Estrogen metabolites (in picomoles per liter) were estimated using inverse probability weighted linear regression, adjusting for potential confounders and stratified on menopausal hormone therapy (MHT) use. Results Among never or former MHT users, current BMI (≥30 vs.
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association of active and sedentary behaviors with postmenopausal Estrogen metabolism
Medicine and Science in Sports and Exercise, 2016Co-Authors: Cher M Dallal, Charles E Matthews, Roni T Falk, Louise A Brinton, Ruth M Pfeiffer, Timothy D. Veenstra, Terryl J Hartman, Jolanta Lissowska, Montserrat Garciaclosas, Gretchen L GierachAbstract:Purpose Physical activity may reduce endogenous Estrogens, but few studies have assessed effects on Estrogen metabolism and none have evaluated sedentary behavior in relation to Estrogen metabolism. We assessed relationships between accelerometer-measured physical activity and sedentary behavior and 15 urinary Estrogens and Estrogen metabolites (EM) among postmenopausal controls from a population-based breast cancer case-control study conducted in Poland (2000-2003). Methods Postmenopausal women (N = 542) were ages 40 to 72 yr and not currently using hormone therapy. Accelerometers, worn for 7 d, were used to derive measures of average activity (counts per day) and sedentary behavior (<100 counts per minute per day). Estrogen metabolites were measured in 12-h urine samples using liquid chromatography-tandem mass spectrometry. Estrogen metabolites were analyzed individually, in metabolic pathways (C-2, -4, or -16), and as ratios relative to parent Estrogens. Geometric means of Estrogen metabolites by tertiles of accelerometer-measures, adjusted for age and body mass, were computed using linear models. Results High activity was associated with lower levels of estrone and estradiol (P trend = 0.01), whereas increased sedentary time was positively associated with these parent Estrogens (P trend = 0.04). Inverse associations were observed between high activity and 2-methoxyestradiol, 4-methoxyestradiol, 17-epiestriol, and 16-epiestriol (P trend = 0.03). Sedentary time was positively associated with methylated catechols in the 2- and 4-hydroxylation pathways (P trend <= 0.04). Women in the highest tertile of activity had increased hydroxylation at the C-2, -4, and -16 sites relative to parent Estrogens (P trend <= 0.02), whereas increased sedentary time was associated with a lower 16-pathway/parent Estrogen ratio (P trend = 0.01). Conclusions Higher activity was associated with lower urinary Estrogens, possibly through increased Estrogen hydroxylation and subsequent metabolism, whereas sedentary behavior may reduce metabolism.
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Estrogen replacement therapy and endometrial cancer risk unresolved issues the endometrial cancer collaborative group
Obstetrics & Gynecology, 1993Co-Authors: Louise A Brinton, R N HooverAbstract:Objective To clarify several unresolved issues regarding the relationship of Estrogens to endometrial cancer risk. Methods We conducted a hospital-based case-control study involving 300 menopausal women newly diagnosed with epithelial endometrial cancer and 207 population controls matched to the cases for age, race, and residence. Results Estrogen use significantly increased endometrial cancer risk (adjusted relative risk [RR] 3.0, 95% confidence interval [CI] 1.7-5.1). Although both short- and long-term use appeared to elevate the risk of early-stage tumors, an effect of Estrogens on late-stage tumors was observed only for long-term use (RR 2.1, 95% CI 0.7-6.4). A small proportion of women reported having used progestogens simultaneously with Estrogens, which was associated with a lower risk (RR 1.8) than use of Estrogens alone (RR 3.4). Although the highest risks were for recent users of Estrogens, persistent excess risks were seen even for those who had discontinued use of 5 or more years. There were no striking relationships according to the type of Estrogen or regimen used, and associations with dose were inconsistent, although women who used low-dose preparations exclusively had the lowest risk. Estrogen injections or creams, used by only 5.9 and 5.1% of the subjects, respectively, were not significant risk factors after adjustment for Estrogen pill use. Women who were thin or who smoked cigarettes appeared to be most adversely affected by Estrogen use. Estrogen users failed to experience the protective effect normally associated with oral contraceptive use. Conclusion The effect of Estrogens on endometrial cancer risk appears to vary both by usage patterns and by patient characteristics.
Eleanor G. Rogan - One of the best experts on this subject based on the ideXlab platform.
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unbalanced Estrogen metabolism in thyroid cancer
International Journal of Cancer, 2013Co-Authors: Muhammad Zahid, Ercole L Cavalieri, Eleanor G. Rogan, Whitney S Goldner, Cheryl L BeselerAbstract:Well-differentiated thyroid cancer most frequently occurs in premenopausal women. Greater exposure to Estrogens may be a risk factor for thyroid cancer. To investigate the role of Estrogens in thyroid cancer, a spot urine sample was obtained from 40 women with thyroid cancer and 40 age-matched controls. Thirty-eight Estrogen metabolites, conjugates and DNA adducts were analyzed by using ultraperformance liquid chromatography/tandem mass spectrometry and the ratio of adducts to metabolites and conjugates was calculated for each sample. The ratio of depurinating Estrogen-DNA adducts to Estrogen metabolites and conjugates significantly differed between cases and controls (p < 0.0001), demonstrating high specificity and sensitivity. These findings indicate that Estrogen metabolism is unbalanced in thyroid cancer and suggest that formation of Estrogen-DNA adducts might play a role in the initiation of thyroid cancer.
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Estrogens as endogenous genotoxic agents dna adducts and mutations
Journal of The National Cancer Institute Monographs, 2000Co-Authors: Ercole L Cavalieri, Eleanor G. Rogan, Joachim G. Liehr, Krystyna Frenkel, Deodutta RoyAbstract:Estrogens induce tumors in laboratory animals and have been associated with breast and uterine cancers in humans. In relation to the role of Estrogens in the induction of cancer, we examine formation of DNA adducts by reactive electrophilic Estrogen metabolites, formation of reactive oxygen species by Estrogens and the resulting indirect DNA damage by these oxidants, and, finally, genomic and gene mutations induced by Estrogens. Quinone intermediates derived by oxidation of the catechol Estrogens 4-hydroxyestradiol or 4-hydroxyestrone may react with purine bases of DNA to form depurinating adducts that generate highly mutagenic apurinic sites. In contrast, quinones of 2-hydroxylated Estrogens produce less harmful, stable DNA adducts. The catechol Estrogen metabolites may also generate potentially mutagenic oxygen radicals by metabolic redox cycling or other mechanisms. Several types of indirect DNA damage are caused by Estrogen-induced oxidants, such as oxidized DNA bases, DNA strand breakage, and adduct formation by reactive aldehydes derived from lipid hydroperoxides. Estradiol and the synthetic Estrogen diethylstilbestrol also induce numerical and structural chromosomal aberrations and several types of gene mutations in cells in culture and in vivo. In conclusion, Estrogens, including the natural hormones estradiol and estrone, must be considered genotoxic carcinogens on the basis of the evidence outlined in this chapter.
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chapter 4 Estrogens as endogenous genotoxic agents dna adducts and mutations
Journal of The National Cancer Institute Monographs, 2000Co-Authors: Ercole L Cavalieri, Eleanor G. Rogan, Joachim G. Liehr, Krystyna Frenkel, Deodutta RoyAbstract:Estrogens induce tumors in laboratory animals and have been associated with breast and uterine cancers in humans. In relation to the role of Estrogens in the induction of cancer, we examine formation of DNA adducts by reactive electrophilic Estrogen metabolites, formation of reactive oxygen species by Estrogens and the resulting indirect DNA damage by these oxidants, and, finally, genomic and gene mutations induced by Estrogens. Quinone intermediates derived by oxidation of the catechol Estrogens 4-hydroxyestradiol or 4-hydroxyestrone may react with purine bases of DNA to form depurinating adducts that generate highly mutagenic apurinic sites. In contrast, quinones of 2-hydroxylated Estrogens produce less harmful, stable DNA adducts. The catechol Estrogen metabolites may also generate potentially mutagenic oxygen radicals by metabolic redox cycling or other mechanisms. Several types of indirect DNA damage are caused by Estrogen-induced oxidants, such as oxidized DNA bases, DNA strand breakage, and adduct formation by reactive aldehydes derived from lipid hydroperoxides. Estradiol and the synthetic Estrogen diethylstilbestrol also induce numerical and structural chromosomal aberrations and several types of gene mutations in cells in culture and in vivo .I n conclusion, Estrogens, including the natural hormones estradiol and estrone, must be considered genotoxic carcinogens on the basis of the evidence outlined in this chapter. [J Natl Cancer Inst Monogr 2000;27:75–93]
Bertil Casslén - One of the best experts on this subject based on the ideXlab platform.
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the g protein coupled Estrogen receptor 1 gper gpr30 does not predict survival in patients with ovarian cancer
Journal of Ovarian Research, 2012Co-Authors: Zuzana Kolkova, Vera Casslén, Emir Henic, Anna Ehinger, Karin Jirström, Sara Ahmadi, Bertil CasslénAbstract:Background Even though ovarian tumors are not generally considered Estrogen-sensitive, Estrogens may still have an impact on ovarian tumor progression. The recently identified trans-membrane Estrogen receptor GPER is involved in rapid Estrogen signaling. Furthermore, it binds selective Estrogen receptor modulators with agonistic effect, which could explain tamoxifen controversies.
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the g protein coupled Estrogen receptor 1 gper gpr30 does not predict survival in patients with ovarian cancer
Journal of Ovarian Research, 2012Co-Authors: Zuzana Kolkova, Vera Casslén, Emir Henic, Anna Ehinger, Karin Jirström, Sara Ahmadi, Bertil CasslénAbstract:Background Even though ovarian tumors are not generally considered Estrogen-sensitive, Estrogens may still have an impact on ovarian tumor progression. The recently identified trans-membrane Estrogen receptor GPER is involved in rapid Estrogen signaling. Furthermore, it binds selective Estrogen receptor modulators with agonistic effect, which could explain tamoxifen controversies.
