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Estrogen metabolite ratio: Is the 2-hydroxyestrone to 16α-hydroxyestrone ratio predictive for breast cancer?

Obi N, Vrieling A, Heinz J, Chang-Claude J - Int J Womens Health (2011)

Bottom Line: Although 16α-hydroxyestrone (16αOHE1) exerts estrogenic activity through covalent estrogen receptor (ER) binding, 2-hydroxyestrone (2OHE1) presumably has antiestrogenic capabilities.For the highest compared with the lowest quantile of urinary EMR, nonsignificant associations suggested at best a weak protective effect in premenopausal but not in postmenopausal breast cancer (range of odds ratios: 0.50-0.75 for premenopausal and 0.71-1.31 for postmenopausal).Uncontrolled factors known to be involved in breast carcinogenesis, such as 4-hydroxyestrone (4OHE1) concentration, may have confounded results for EMR.

View Article: PubMed Central - PubMed

Affiliation: University Cancer Center Hamburg (UCCH)/Hubertus Wald Tumor Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;

ABSTRACT
Experimental studies have shown that two main estrogen metabolites hydroxylated by CYP1A1 and CYP1B1 in the breast differentially affect breast cell proliferation and carcinogenesis. Although 16α-hydroxyestrone (16αOHE1) exerts estrogenic activity through covalent estrogen receptor (ER) binding, 2-hydroxyestrone (2OHE1) presumably has antiestrogenic capabilities. The ratio of 2OHE1 to 16αOHE1 represents the relative dominance of one pathway over the other and is believed to be modifiable by diet. It was hypothesized that women with or at high risk of breast cancer have a lower estrogen metabolite ratio (EMR) compared with women without breast cancer. We conducted a systematic review on the EMR as a predictor for breast cancer. A total of nine studies (six prospective and three retrospective) matched our inclusion criteria, comprising 682 premenopausal cases (1027 controls) and 1189 postmenopausal cases (1888 controls). For the highest compared with the lowest quantile of urinary EMR, nonsignificant associations suggested at best a weak protective effect in premenopausal but not in postmenopausal breast cancer (range of odds ratios: 0.50-0.75 for premenopausal and 0.71-1.31 for postmenopausal). Circulating serum/plasma EMR was not associated with breast cancer risk. Associations were inconclusive for receptor subtypes of breast cancer. Uncontrolled factors known to be involved in breast carcinogenesis, such as 4-hydroxyestrone (4OHE1) concentration, may have confounded results for EMR. Results of the prospective studies do not support the hypothesis that EMR can be used as a predictive marker for breast cancer risk. Future research should concentrate on profiles of estrogen metabolites, including 4OHE1, to gain a more complete picture of the relative importance of single metabolites for breast cancer.

No MeSH data available.


Related in: MedlinePlus

Funnel plot of risk estimates of nine included33,36,38–44 and two excluded studies16,17 (separate RR/OR for menopausal status, where available).Abbreviations: RR, risk ratio; OR, odds ratio.
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f2-ijwh-3-037: Funnel plot of risk estimates of nine included33,36,38–44 and two excluded studies16,17 (separate RR/OR for menopausal status, where available).Abbreviations: RR, risk ratio; OR, odds ratio.

Mentions: Exclusion of two earlier small studies,16,17 which found strong inverse associations for EMR, may have led to certain bias toward results, but these studies were not included due to flaws in design or reporting. A funnel plot (Figure 2), including these studies, suggested that there might have been publication bias in this early phase. Another larger excluded study that assessed only single estrogen metabolites in serum of postmenopausal hormone therapy nonusers did not report statistically significant associations with breast cancer risk.47 Though not necessarily, it is likely that the EMR was also not associated with breast cancer in this study.


Estrogen metabolite ratio: Is the 2-hydroxyestrone to 16α-hydroxyestrone ratio predictive for breast cancer?

Obi N, Vrieling A, Heinz J, Chang-Claude J - Int J Womens Health (2011)

Funnel plot of risk estimates of nine included33,36,38–44 and two excluded studies16,17 (separate RR/OR for menopausal status, where available).Abbreviations: RR, risk ratio; OR, odds ratio.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3039007&req=5

f2-ijwh-3-037: Funnel plot of risk estimates of nine included33,36,38–44 and two excluded studies16,17 (separate RR/OR for menopausal status, where available).Abbreviations: RR, risk ratio; OR, odds ratio.
Mentions: Exclusion of two earlier small studies,16,17 which found strong inverse associations for EMR, may have led to certain bias toward results, but these studies were not included due to flaws in design or reporting. A funnel plot (Figure 2), including these studies, suggested that there might have been publication bias in this early phase. Another larger excluded study that assessed only single estrogen metabolites in serum of postmenopausal hormone therapy nonusers did not report statistically significant associations with breast cancer risk.47 Though not necessarily, it is likely that the EMR was also not associated with breast cancer in this study.

Bottom Line: Although 16α-hydroxyestrone (16αOHE1) exerts estrogenic activity through covalent estrogen receptor (ER) binding, 2-hydroxyestrone (2OHE1) presumably has antiestrogenic capabilities.For the highest compared with the lowest quantile of urinary EMR, nonsignificant associations suggested at best a weak protective effect in premenopausal but not in postmenopausal breast cancer (range of odds ratios: 0.50-0.75 for premenopausal and 0.71-1.31 for postmenopausal).Uncontrolled factors known to be involved in breast carcinogenesis, such as 4-hydroxyestrone (4OHE1) concentration, may have confounded results for EMR.

View Article: PubMed Central - PubMed

Affiliation: University Cancer Center Hamburg (UCCH)/Hubertus Wald Tumor Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;

ABSTRACT
Experimental studies have shown that two main estrogen metabolites hydroxylated by CYP1A1 and CYP1B1 in the breast differentially affect breast cell proliferation and carcinogenesis. Although 16α-hydroxyestrone (16αOHE1) exerts estrogenic activity through covalent estrogen receptor (ER) binding, 2-hydroxyestrone (2OHE1) presumably has antiestrogenic capabilities. The ratio of 2OHE1 to 16αOHE1 represents the relative dominance of one pathway over the other and is believed to be modifiable by diet. It was hypothesized that women with or at high risk of breast cancer have a lower estrogen metabolite ratio (EMR) compared with women without breast cancer. We conducted a systematic review on the EMR as a predictor for breast cancer. A total of nine studies (six prospective and three retrospective) matched our inclusion criteria, comprising 682 premenopausal cases (1027 controls) and 1189 postmenopausal cases (1888 controls). For the highest compared with the lowest quantile of urinary EMR, nonsignificant associations suggested at best a weak protective effect in premenopausal but not in postmenopausal breast cancer (range of odds ratios: 0.50-0.75 for premenopausal and 0.71-1.31 for postmenopausal). Circulating serum/plasma EMR was not associated with breast cancer risk. Associations were inconclusive for receptor subtypes of breast cancer. Uncontrolled factors known to be involved in breast carcinogenesis, such as 4-hydroxyestrone (4OHE1) concentration, may have confounded results for EMR. Results of the prospective studies do not support the hypothesis that EMR can be used as a predictive marker for breast cancer risk. Future research should concentrate on profiles of estrogen metabolites, including 4OHE1, to gain a more complete picture of the relative importance of single metabolites for breast cancer.

No MeSH data available.


Related in: MedlinePlus