Urinary estrogen metabolites and breast cancer: a combined analysis of individual level data

Cher M. Dallal; Roslyn A. Stone; Jane A. Cauley; Roberta B. Ness; Victor G. Vogel; Ian Fentiman; Jay H. Fowke; Vittorio Krogh; Steffen Loft; Elaine N. Meilahn; Paola Muti; Anja Olsen; Kim Overvad; Sabina Sieri; Anne Tjonneland; Giske Ursin; Anja Wellejus; Emanuela Taioli

doi:10.5301/JBM.2012.9353

Urinary estrogen metabolites and breast cancer: a combined analysis of individual level data

Cher M. Dallal^*, Roslyn A. Stone, Jane A. Cauley, Roberta B. Ness, Victor G. Vogel, Ian Fentiman, Jay H. Fowke, Vittorio Krogh, Steffen Loft, Elaine N. Meilahn, Paola Muti, Anja Olsen, Kim Overvad, Sabina Sieri, Anne Tjonneland, Giske Ursin, Anja Wellejus, Emanuela Taioli

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

Background: Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16 alpha-hydroxyestrone (16 alpha-OHE1), and their ratio (2:16 alpha-OHE1) in relation to breast cancer risk.

Methods: Primary data on 726 premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108 postmenopausal women (385 invasive breast cancer cases and 723 controls) were analyzed. Urinary estrogen metabolites were measured using enzyme linked immunosorbent assays. Study-specific and combined multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated based on tertiles of estrogen metabolites. Multinomial logistic regression models were fit according to hormone receptor status.

Results: Higher premenopausal 2:16 alpha-OHE1 was suggestive of reduced breast cancer risk overall (study-adjusted ORIIIvsI = 0.80; 95% CI: 0.49-1.32) and for estrogen receptor negative (ER-) subtype (ORIIIvsI=0.33; 95% CI: 0.13-0.84). Among postmenopausal women, 2:16 alpha-OHE1 was unrelated to breast cancer risk (study-adjusted ORIIIvsI=0.93; 95% CI: 0.65-1.33); however, the association between 2-OHE1 and risk varied by body mass index (p-interaction=0.003).

Conclusions: Premenopausal urinary 2:16 alpha-OHE1 may play a role in breast carcinogenesis; however, larger studies are needed. Our findings do not support reduced breast cancer risk with higher postmenopausal 2:16 alpha-OHE1 overall, although obesity may modify associations with 2-OHE1.

Original language	English
Pages (from-to)	3-16
Number of pages	14
Journal	International Journal of Biological Markers
Volume	28
Issue number	1
DOIs	https://doi.org/10.5301/JBM.2012.9353
Publication status	Published - Jan 2013

Keywords

Epidemiology
Estrogen metabolite ratio
Menopause
ENDOGENOUS ESTRADIOL METABOLITES
PROGESTERONE-RECEPTOR STATUS
POSTMENOPAUSAL WOMEN
PREMENOPAUSAL WOMEN
MASS-SPECTROMETRY
SEX-HORMONES
RISK-FACTORS
16-ALPHA-HYDROXYESTRONE
CELLS
RATIO

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.5301/JBM.2012.9353

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Dallal, C. M., Stone, R. A., Cauley, J. A., Ness, R. B., Vogel, V. G., Fentiman, I., Fowke, J. H., Krogh, V., Loft, S., Meilahn, E. N., Muti, P., Olsen, A., Overvad, K., Sieri, S., Tjonneland, A., Ursin, G., Wellejus, A., & Taioli, E. (2013). Urinary estrogen metabolites and breast cancer: a combined analysis of individual level data. International Journal of Biological Markers, 28(1), 3-16. https://doi.org/10.5301/JBM.2012.9353

@article{8551b15361f44d15b5fe7f053419758c,

title = "Urinary estrogen metabolites and breast cancer: a combined analysis of individual level data",

abstract = "Background: Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16 alpha-hydroxyestrone (16 alpha-OHE1), and their ratio (2:16 alpha-OHE1) in relation to breast cancer risk.Methods: Primary data on 726 premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108 postmenopausal women (385 invasive breast cancer cases and 723 controls) were analyzed. Urinary estrogen metabolites were measured using enzyme linked immunosorbent assays. Study-specific and combined multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated based on tertiles of estrogen metabolites. Multinomial logistic regression models were fit according to hormone receptor status.Results: Higher premenopausal 2:16 alpha-OHE1 was suggestive of reduced breast cancer risk overall (study-adjusted ORIIIvsI = 0.80; 95% CI: 0.49-1.32) and for estrogen receptor negative (ER-) subtype (ORIIIvsI=0.33; 95% CI: 0.13-0.84). Among postmenopausal women, 2:16 alpha-OHE1 was unrelated to breast cancer risk (study-adjusted ORIIIvsI=0.93; 95% CI: 0.65-1.33); however, the association between 2-OHE1 and risk varied by body mass index (p-interaction=0.003).Conclusions: Premenopausal urinary 2:16 alpha-OHE1 may play a role in breast carcinogenesis; however, larger studies are needed. Our findings do not support reduced breast cancer risk with higher postmenopausal 2:16 alpha-OHE1 overall, although obesity may modify associations with 2-OHE1.",

keywords = "Epidemiology, Estrogen metabolite ratio, Menopause, ENDOGENOUS ESTRADIOL METABOLITES, PROGESTERONE-RECEPTOR STATUS, POSTMENOPAUSAL WOMEN, PREMENOPAUSAL WOMEN, MASS-SPECTROMETRY, SEX-HORMONES, RISK-FACTORS, 16-ALPHA-HYDROXYESTRONE, CELLS, RATIO",

author = "Dallal, {Cher M.} and Stone, {Roslyn A.} and Cauley, {Jane A.} and Ness, {Roberta B.} and Vogel, {Victor G.} and Ian Fentiman and Fowke, {Jay H.} and Vittorio Krogh and Steffen Loft and Meilahn, {Elaine N.} and Paola Muti and Anja Olsen and Kim Overvad and Sabina Sieri and Anne Tjonneland and Giske Ursin and Anja Wellejus and Emanuela Taioli",

year = "2013",

month = jan,

doi = "10.5301/JBM.2012.9353",

language = "English",

volume = "28",

pages = "3--16",

journal = "International Journal of Biological Markers",

issn = "0393-6155",

publisher = "Wichtig Publishing",

number = "1",

}

Dallal, CM, Stone, RA, Cauley, JA, Ness, RB, Vogel, VG, Fentiman, I, Fowke, JH, Krogh, V, Loft, S, Meilahn, EN, Muti, P, Olsen, A, Overvad, K, Sieri, S, Tjonneland, A, Ursin, G, Wellejus, A & Taioli, E 2013, 'Urinary estrogen metabolites and breast cancer: a combined analysis of individual level data', International Journal of Biological Markers, vol. 28, no. 1, pp. 3-16. https://doi.org/10.5301/JBM.2012.9353

TY - JOUR

T1 - Urinary estrogen metabolites and breast cancer

T2 - a combined analysis of individual level data

AU - Dallal, Cher M.

AU - Stone, Roslyn A.

AU - Cauley, Jane A.

AU - Ness, Roberta B.

AU - Vogel, Victor G.

AU - Fentiman, Ian

AU - Fowke, Jay H.

AU - Krogh, Vittorio

AU - Loft, Steffen

AU - Meilahn, Elaine N.

AU - Muti, Paola

AU - Olsen, Anja

AU - Overvad, Kim

AU - Sieri, Sabina

AU - Tjonneland, Anne

AU - Ursin, Giske

AU - Wellejus, Anja

AU - Taioli, Emanuela

PY - 2013/1

Y1 - 2013/1

N2 - Background: Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16 alpha-hydroxyestrone (16 alpha-OHE1), and their ratio (2:16 alpha-OHE1) in relation to breast cancer risk.Methods: Primary data on 726 premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108 postmenopausal women (385 invasive breast cancer cases and 723 controls) were analyzed. Urinary estrogen metabolites were measured using enzyme linked immunosorbent assays. Study-specific and combined multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated based on tertiles of estrogen metabolites. Multinomial logistic regression models were fit according to hormone receptor status.Results: Higher premenopausal 2:16 alpha-OHE1 was suggestive of reduced breast cancer risk overall (study-adjusted ORIIIvsI = 0.80; 95% CI: 0.49-1.32) and for estrogen receptor negative (ER-) subtype (ORIIIvsI=0.33; 95% CI: 0.13-0.84). Among postmenopausal women, 2:16 alpha-OHE1 was unrelated to breast cancer risk (study-adjusted ORIIIvsI=0.93; 95% CI: 0.65-1.33); however, the association between 2-OHE1 and risk varied by body mass index (p-interaction=0.003).Conclusions: Premenopausal urinary 2:16 alpha-OHE1 may play a role in breast carcinogenesis; however, larger studies are needed. Our findings do not support reduced breast cancer risk with higher postmenopausal 2:16 alpha-OHE1 overall, although obesity may modify associations with 2-OHE1.

AB - Background: Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16 alpha-hydroxyestrone (16 alpha-OHE1), and their ratio (2:16 alpha-OHE1) in relation to breast cancer risk.Methods: Primary data on 726 premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108 postmenopausal women (385 invasive breast cancer cases and 723 controls) were analyzed. Urinary estrogen metabolites were measured using enzyme linked immunosorbent assays. Study-specific and combined multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated based on tertiles of estrogen metabolites. Multinomial logistic regression models were fit according to hormone receptor status.Results: Higher premenopausal 2:16 alpha-OHE1 was suggestive of reduced breast cancer risk overall (study-adjusted ORIIIvsI = 0.80; 95% CI: 0.49-1.32) and for estrogen receptor negative (ER-) subtype (ORIIIvsI=0.33; 95% CI: 0.13-0.84). Among postmenopausal women, 2:16 alpha-OHE1 was unrelated to breast cancer risk (study-adjusted ORIIIvsI=0.93; 95% CI: 0.65-1.33); however, the association between 2-OHE1 and risk varied by body mass index (p-interaction=0.003).Conclusions: Premenopausal urinary 2:16 alpha-OHE1 may play a role in breast carcinogenesis; however, larger studies are needed. Our findings do not support reduced breast cancer risk with higher postmenopausal 2:16 alpha-OHE1 overall, although obesity may modify associations with 2-OHE1.

KW - Epidemiology

KW - Estrogen metabolite ratio

KW - Menopause

KW - ENDOGENOUS ESTRADIOL METABOLITES

KW - PROGESTERONE-RECEPTOR STATUS

KW - POSTMENOPAUSAL WOMEN

KW - PREMENOPAUSAL WOMEN

KW - MASS-SPECTROMETRY

KW - SEX-HORMONES

KW - RISK-FACTORS

KW - 16-ALPHA-HYDROXYESTRONE

KW - CELLS

KW - RATIO

U2 - 10.5301/JBM.2012.9353

DO - 10.5301/JBM.2012.9353

M3 - Article

SN - 0393-6155

VL - 28

SP - 3

EP - 16

JO - International Journal of Biological Markers

JF - International Journal of Biological Markers

IS - 1

ER -

Urinary estrogen metabolites and breast cancer: a combined analysis of individual level data

Abstract

Keywords

UN SDGs

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