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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

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

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

breast cancer risk 2:16alpha-OHE1 estrogen metabolism ratio

shared by Nathan Goodyear on 23 Aug 11 - No Cached
  • Nathan Goodyear on 23 Aug 11
     
    in this study, estrogen metabolite ratio of 2:16alpha-OHE1 was found to not be predictive of breast cancer risk
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

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

Postmenopausal circulating levels of 2- and 16α-hydroxyestrone and risk of en... - 0 views

www.ncbi.nlm.nih.gov/...PMC3241553

estrogen metabolism 2-hydroxyestrone 4-hydroxyestrone estrogen metabolites cancer uterine cancer endometrial cancer hormones 2:16alpha-OHE1 2:16

shared by Nathan Goodyear on 07 Oct 15 - No Cached
  • our results do not support the hypothesis that greater metabolism of oestrogen via the 2-OH pathway, relative to the 16α-OH pathway, protects against endometrial cancer. Indeed our results are more suggestive of an increase in risk, rather than a decrease, with higher levels of 2-OHE1
  • women with a higher 2-OHE1 : 16α-OHE1 ratio did not have a decreased risk of endometrial cancer as compared with women with a lower ratio
  • The findings from this first prospective epidemiological study of oestrogen metabolites and endometrial cancer are in line with results from prospective studies on breast cancer, another oestrogen-related cancer. None of the seven studies on breast cancer reported significant associations overall
  • ...4 more annotations...
  • On the whole, prospective epidemiological data do not support the hypothesis that the 2-hydroxyestrogen pathway is protective, and the 16α-hydroxyestrogen pathway harmful, in hormone-dependent cancers
  • Both 2- and 4-hydroxyestrogens are catecholestrogens, and it has been suggested that catecholestrogens increase risk of oestrogen-mediated cancers through direct genotoxic effects, rather than through stimulation of cell proliferation via binding to oestrogen receptors
  • the evidence is stronger for 4-hydroxyestrogens than for 2-hydroxyestrogens
  • a significant increase in risk of breast cancer with levels of 2-OHE1 has also been reported previously, although it was limited to hormone receptor-negative tumours
  • Nathan Goodyear on 07 Oct 15
     
    2:16 hydroxyestrone ratio not associated with uterine cancer risk.
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

Do urinary oestrogen metabolites predict breast ca... [Br J Cancer. 1998] - PubMed result - 0 views

www.ncbi.nlm.nih.gov/...9820189

estrogen metabolism breast cancer 2:16alpha-OHE1

shared by Nathan Goodyear on 23 Aug 11 - No Cached
  • post-menopausal (but not premenopausal) women at baseline who went on to develop breast cancer showed about a 15% lower 2:16alpha-OHE1 ratio than matched control subjects
  • Nathan Goodyear on 23 Aug 11
     
    can the pathway of estrogen metabolism help to predict postmenopausal breast cancer?  according to this study, yes.
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

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

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.
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