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Nathan Goodyear

Circulating 2-hydroxy and 16-α hydroxy estrone levels and risk of breast canc... - 1 views

www.ncbi.nlm.nih.gov/...PMC2562592

estrogen metabolism menopause post-menopause post menopause estrogen metabolite 2-OH-estrone 16-alpha-OH-estrone 2:16alpha-OH estrone breast cancer risk hormone hormones

shared by Nathan Goodyear on 21 Aug 14 - No Cached
  • 2-OH estrogens bind to the estrogen receptor (ER) with affinity equivalent to or greater than estradiol
  • previous prospective studies have not observed any significant associations with either 2-OH or 16α-OH estrone or the ratio of the two metabolites and breast cancer risk overall.
    • Nathan Goodyear
      Nathan Goodyear on 08 Oct 15
       
      whether that risk is increased or decreased
  • it has been hypothesized that metabolism favoring the 2-OH over the 16α-OH pathway may be inversely associated with breast cancer risk (28).
  • ...24 more annotations...
  • they may act as only weak mitogens (14, 15), or as inhibitors of proliferation
  • No significant associations have been observed between 2-OH estrone and breast cancer risk
  • While 16α-OH estrone binds to the ER with lower affinity than estradiol, it binds covalently (18-20) and once bound, fails to down-regulate the receptor (21). Thus, 16α-OH estrone stimulates cell proliferation in a manner comparable to estradiol in ER+ breast cancer cell lines
  • In this large prospective study of 2-OH and 16α-OH estrone metabolites and breast cancer risk, we did not observe any significant associations overall with either individual metabolite or with the ratio of the two metabolites
  • we observed positive associations with 2-OH estrone and the 2:16α-OH estrone ratio among women with lower BMI and women with ER-/PR-tumors,
  • To date, several epidemiologic studies have examined the association between the 2-OH and 16α-OH estrogen metabolites and breast cancer risk with inconclusive results.
  • circulating estrogen levels have been associated more strongly with ER+/PR+ tumors than with ER-/PR- tumors
  • our results do not support the hypothesis that metabolism favoring the 2-OH estrone pathway is more beneficial to breast cancer risk than that favoring the 16α-OH estrone pathway
  • we observed significant positive associations of both 2-OH estrone and the 2:16α-OH estrone ratio with ER-/PR-tumors
  • Three (30, 32, 33) of four (30-33) studies observed RRs above 1 for the association between 16α-OH estrone and breast cancer risk (range of RRs=1.23-2.47); none of the point estimates was statistically significant though one trend was suggestive
  • based on animal studies, 2-OH estrone and the 2:16α-OH estrone ratio have been hypothesized to be inversely associated with breast cancer risk
  • No significant associations have been observed between 2-OH estrone, 16α-OH estrone, or the 2:16α-OH estrone ratio and breast cancer risk and the direction of the estimates is not consistent across studies.
    • Nathan Goodyear
      Nathan Goodyear on 08 Oct 15
       
      better worded is no consistent, significant associations.   There are some studies that point to the 16 catecholestrogen and increased cancer risk; limited studies show negative effects of 2 catecholestrogens on cancer risk and prospective studies available pretty much dispel the idea that the 2:16 ratio has an risk predictability.
  • we observed a suggestive inverse association with 16α-OH estrone and a significant positive association with the 2:16α-OH estrone ratio among lean women, suggesting possible associations in a low estrogen environment.
  • 16α-OH estrone increases unscheduled DNA synthesis in mouse mammary cells (27) and hence also may be genotoxic
  • Although 2-OH estrogens are capable of redox cycling, the semiquinones and quinones (i.e., the oxidized forms) form stable DNA adducts that are reversible without DNA destruction
  • In our population of PMH nonusers, we observed no associations with ER+/PR+ tumors, but significant positive associations with 2-OH estrone and the 2:16α-OH estrone ratio among women with ER-/PR- tumors
    • Nathan Goodyear
      Nathan Goodyear on 08 Oct 15
       
      one of the few studies to find this association between 2 catecholestrogens and the 2:16 ratio and ER-/PR-tumors
  • Animal and in vitro studies have shown that hydroxy estrogens can induce DNA damage either directly, through the formation of quinones and DNA adducts, or indirectly, through redox cycling and the generation of reactive oxygen species
    • Nathan Goodyear
      Nathan Goodyear on 08 Oct 15
       
      genotoxic via directe DNA adducts and indirectly via ROS; this is in addition to the proliferative effect
  • we observed a significant positive association between the 2:16α-OH estrone ratio and breast cancer risk among lean women
  • No significant associations have been observed with the 2:16α-OH estrone ratio
  • In the Danish study, no associations were observed with either ER+ or ER- tumors among PMH nonusers
  • significant positive associations with 2-OH estrone and the 2:16α-OH estrone ratio were observed among PMH users with ER+, but not ER-, tumors
  • it is possible that the genotoxicity of 2-OH estrone plays a role in hormone receptor negative tumors
  • 4-OH estrogens have a greater estrogenic potential than 2-OH estrogens, given the lower dissociation rate from estrogen receptors compared with estradiol (61), and are potentially more genotoxic since the quinones form unstable adducts, leading to depurination and mutation in vitro and in vivo
  • the balance between the catechol (i.e., 2-OH and 4-OH) and methoxy (i.e., 2-Me and 4-Me) estrogens may impact risk
  • Nathan Goodyear on 21 Aug 14
     
    The risks of estrogen metabolism are not clear cut.  Likely never will be due to the complexity of individual metabolism.  This study found no correlation between 2OH-Estrone and 2OH:16alpha-Estrone and breast cancer risk in ER+/PR+ breast cancer.  Translated: no benefit in breast cancer risk in 2OH-Estrone metabolism or increased 2OH:16alpha estrone metabolism.  There was a positive association between 2OH-Estrone and 2:16alpha-Estrone in women with ER-/PR- tumors and low BMI.
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Nathan Goodyear

Circulating Estrogen Metabolites and Risk for Breast Cancer in Premenopausal Women - 0 views

cebp.aacrjournals.org/...2273.short

estrogen metabolism estrogen metabolite estrogen metabolism breast cancer 2-OH-estrone 16alpha-OH-estrone estrone metabolite metabolites

shared by Nathan Goodyear on 21 Aug 14 - No Cached
  • Nathan Goodyear on 21 Aug 14
     
    Epidemiologic study finds no association between increased 2OH-estrone metabolism and increased 2OH:16alphaOH-estrone metabolism and a reduction in breast cancer risk.
Nathan Goodyear

Circulating Estrogen Metabolites and Risk for Breast Cancer in Premenopausal Women - 0 views

www.ncbi.nlm.nih.gov/...PMC3000741

estrogen metabolites estrogen metabolism estrogen 2-OH-estrone 16-alpha-OH-estrone cancer breast cancer women

shared by Nathan Goodyear on 18 Sep 15 - No Cached
  • Nathan Goodyear on 18 Sep 15
     
    no statistical significant association between 2OH-estrone, 16-alpha-OH-estrone, and their ratio found to be associated with increased breast cancer risk in pre menopause women.
Nathan Goodyear

Estrogen metabolite ratio: is the 2-OH estrone to 16alph-OH estrone ratio predictive of... - 0 views

www.ncbi.nlm.nih.gov/...ijwh-3-037.pdf

estrogen metabolism cancer breast prostate metabolites 2-OH estrone 16alpha-OH

shared by Nathan Goodyear on 17 Feb 12 - No Cached
  • Nathan Goodyear on 17 Feb 12
     
    This is a recent review of the literature regarding estrogen metabolism. It has been proposed that 2:16 OH estrone ratio is predictive of breast, prostate cancer. This study does not find that association
Nathan Goodyear

Estrogen Metabolism and Risk of Breast Cancer in Postmenopausal Women - 0 views

www.ncbi.nlm.nih.gov/...PMC3283536

estrogen metabolism estrogen metabolism breast cancer breast cancer

shared by Nathan Goodyear on 14 Oct 13 - No Cached
  • The ratio of the 2-hydroxylation pathway to parent estrogens was associated with a statistically significantly decreased risk of breast cancer
  • In this study, this ratio was more strongly associated with the risk of breast cancer compared with the ratio of 2-hydroxylation pathway to 16-hydroxylation pathway or unconjugated estradiol alone
  • 2-hydroxylation pathway catechols have relatively low affinities for estrogen receptors (4) and are rapidly cleared from circulation
  • ...6 more annotations...
  • In this study, the ratio of the 2-hydroxylation pathway to the 16-hydroxylation pathway was associated with a non-statistically significantly decreased risk of breast cancer
  • In this study, the ratio of catechols to methylated catechols in the 4-hydroxylation pathway was associated with statistically significantly increased risk of breast cancer.
  • This result is consistent with the hypothesis that mutagenic quinones derived from 4-hydroxylation pathway catechols contribute to pathogenesis of postmenopausal breast cancer.
  • Catechols in both the 2- and 4-hydroxylation pathways can be oxidized to form quinones; these reactive electrophiles can then react with DNA to form a variety of adducts
  • Methylation of the catechols prevents their conversion to reactive quinones
  • the most common DNA adducts derived from 4-hydroxylation pathway catechols are depurinating and highly mutagenic (7,40), most of those derived from 2-hydroxylation pathway catechols are stable and can be repaired with little error
  • Nathan Goodyear on 14 Oct 13
     
    Lower 2-OH estrone metabolism associated with lower risk of breast cancer, but 4-OH estrone associated with increased risk of breast cancer.
Nathan Goodyear

Estrogen Metabolism and Breast Cancer : Epidemiology - 0 views

journals.lww.com/...lism_and_Breast_Cancer.15.aspx

estrogen metabolism estrogen metabolism estrogen metabolite metabolite metabolites breast cancer 2-OH-estrone 16alpha-OH-estrone 2:16alpha-OHE1

shared by Nathan Goodyear on 21 Aug 14 - No Cached
  • Nathan Goodyear on 21 Aug 14
     
    Maybe the risks of estrogen metabolism is age dependent?  This Long Island Breast Cancer Study Project found that an increased 2:16alphOH-estrone ratio was associated with a reduced premenopausal, invasive breast cancer risk.  This association declined when looked at in postmenopausal women.
Nathan Goodyear

Estrogen metabolite ratio: Is the 2-hydroxyestrone to 16α-hydroxyestrone rati... - 0 views

www.ncbi.nlm.nih.gov/...PMC3039007

breast cancer 2-OH-estrone 2-OH 4-OH 2:16alpha-OHE1 2:16 estrogen metabolism

shared by Nathan Goodyear on 02 Jan 13 - No Cached
  • A recent study of nine patients concluded that the urinary EMR is a good approximation for breast tissue EMR
  • A single study in young women not using oral contraceptives found fair correlation coefficients between urinary and plasma EMR
  • All of nine properly designed epidemiological studies (six prospective case-control studies and three retrospective studies) failed to show a significant relationship between urinary or circulating EMR (2OHE1/16αOHE1) and breast cancer risk
  • ...2 more annotations...
  • premenopausal studies on urinary EMR have suggested a potentially weak inverse relationship, associations were not significantly different compared with postmenopausal or overall combined studies
  • at present, there is no evidence that the EMR can predict breast cancer risk
  • Nathan Goodyear on 02 Jan 13
     
    The 2:16 OH estrone pathway is shown to not be predictive biomarker for breast cancer.
Nathan Goodyear

Urinary estrogen metabolites in women at high risk for breast cancer - 0 views

carcin.oxfordjournals.org/...1532.full

breast cancer CA estrogen metabolism 2:16 OHE 2-OH-estrone 16-alpha-OH-estrone

shared by Nathan Goodyear on 10 May 12 - No Cached
  • obesity has also been linked to preferential estrogen metabolism via the 16-alpha-hydroxylation pathway; thus, a prediction of the mechanism by which obesity could increase breast cancer risk would be through a lowering of the 2:16 ratio in favor of the 16 pathway
  • increased BMI was associated with a lower 2:16 OHE ratio
  • Our data show a significant association between alcohol use, defined as at least one drink per day or an average of seven per week, and 2:16 OHE ratio
  • ...10 more annotations...
  • An alcohol-induced rise in estrogens as a consequence of alcohol catabolism in the liver has been reported
  • The only study that looked at the association between alcohol and wine consumption in healthy women did not report a clear association
  • smoking has been reported to increase induction of the 2-hydroxylation metabolic pathway (24). However, the few epidemiological studies conducted on healthy women showed no difference in estrogen metabolites with smoking status (22) or smoking dose (20), in line with our findings.
  • Family history of a first-degree family member with breast cancer confers a 2- to 4-fold risk of developing breast cancer
  • 16% of breast cancers are due to unidentified hereditary factors
  • Estrogen metabolism occurs through enzymes whose activity is determined by the presence of specific genetic polymorphisms, thus can be defined as unique to each individual.
  • the metabolism is also influenced by a number of environmental factors, which change over a lifetime
  • significantly lower 2:16 OHE ratio in women who have known breast cancer risk factors compared with healthy women
  • There was an additional significant association specifically with BMI and alcohol use, which also supports the evidence that these factors affect estrogen metabolism
  • Profiling estrogen metabolites may identify women who are more likely to develop breast cancer within a population of women with known risk factors
  • Nathan Goodyear on 10 May 12
     
    urinary estrogen metabolites shown to provide insight into breast cancer risk.  This study suggested that a low 2:16 OHE ratio increase breast cancer risk.
Nathan Goodyear

Urinary Hydroxyestrogens and Breast Cancer Risk among Postmenopausal Women: A Prospecti... - 0 views

cebp.aacrjournals.org/...2137.short

estrogen metabolism estrogen metabolism estrone breast cancer risk post-menopause post menopause HRT hormone therapy 2-OH-estrone

shared by Nathan Goodyear on 21 Aug 14 - No Cached
  • Nathan Goodyear on 21 Aug 14
     
    study finds increases risk of breast cancer in postmenopausal women on HRT with increased 2OH-estrone metabolism.  Confusing?
Nathan Goodyear

Hormone Therapy, Estrogen Metabolism, and Risk of Breast Cancer in the Women's Health I... - 0 views

www.ncbi.nlm.nih.gov/...PMC3493689

breast cancer estrogen metabolites 2-OH-estrone 2:16 cancer hormones estrogen

shared by Nathan Goodyear on 11 Sep 15 - No Cached
  • These results demonstrate that although 16α-OHE1 was increased more by E+P than by E-alone, the increase in the 2:16 ratio was similar for both HT regimens, due to ~4-fold greater increase in 2OHE-1 than 16α-OHE1 for both HT regimens
  • baseline and 1 year change in 16α-OHE1 showed little relationship to incident breast cancer
  • higher baseline 2-OHE1 and the 2:16 ratio were modestly associated with higher odds of incident breast cancer, but larger 1 year increase in 2-OHE-1 and the 2:16 ratio were also weakly associated with lower odds of breast cancer
  • Nathan Goodyear on 11 Sep 15
     
    Good review of the data from the WHI-HT on estrogen metabolites and breast cancer risk.  Increased 2-OHestrone and 2:16 ratio without statistical significance reached.
Nathan Goodyear

http://joe.endocrinology-journals.org/content/167/2/281.full.pdf - 0 views

joe.endocrinology-journals.org/...281.full.pdf

estrogen metabolites 4-hydroxyestrone cancer estrogen hormones 2-hydroxyestrone 2-OH-estrone 4-OH-estrone

shared by Nathan Goodyear on 16 Jul 15 - No Cached
  • Nathan Goodyear on 16 Jul 15
     
    good discussion of the estrogen metabolites and increased estrogenic activity; including cancer risk.  Particular attention is given to the 4-hydroxyestrone metabolite.
Nathan Goodyear

Estrogen Metabolism and Risk of Breast Cancer in Postmenopausal Women - 0 views

jnci.oxfordjournals.org/...326.full

estrogen metabolism cancer breast cancer estrogen metabolites

shared by Nathan Goodyear on 16 Jul 15 - No Cached
  • Nathan Goodyear on 16 Jul 15
     
    Get article on estrogen metabolism/metabolites and their effects on the risk of breast cancer in post menopause women.  This article brings to light new information: 2:16alpha estrone ratio is not a great predicted of risk, 2-OH and 4-OH metabolites can form quinone intermediates...
Nathan Goodyear

Potential Mechanisms of Estrogen Quinone Carcinogenesis - 0 views

www.ncbi.nlm.nih.gov/...PMC2556295

estrogen metabolites estrogen quinones 4-OH-estrone cancer hormones

shared by Nathan Goodyear on 19 Sep 15 - No Cached
  • 4-hydroxyestrone/estradiol was found to be carcinogenic in the male Syrian golden hamster kidney tumor model, whereas, 2-hydroxylated metabolites were without activity
  • 4-hydroxyestradiol induced uterine tumors in 66% of CD-1 mice; whereas, mice treated with 2-hydroxyestradiol or 17β-estradiol had much lower uterine tumor incidence
  • DNA adducts of catechol estrogen quinones have been detected in the mammary glands of ACI rats treated with 4-hydroxyestradiol or it’s quinone
  • Nathan Goodyear on 19 Sep 15
     
    great read on the proposed mechanisms of how estrogen metabolites produce quinone intermediates that are carcinogenic.
Nathan Goodyear

Relationship of serum estrogens and estrogen metabolites to postmenopausal breast cance... - 0 views

www.ncbi.nlm.nih.gov/...PMC4053199

breast cancer cancer estrogen metabolites 2-OH-estrone 2-hydroxyestrone estrogen

shared by Nathan Goodyear on 16 Sep 15 - No Cached
  • Nathan Goodyear on 16 Sep 15
     
    Increased metabolism down the 2 hydroxylation pathway appears to reduce postmenopausal breast cancer risk.
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