Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 May 18;108(10):djw103.
doi: 10.1093/jnci/djw103. Print 2016 Oct.

Endogenous Estrogens, Estrogen Metabolites, and Breast Cancer Risk in Postmenopausal Chinese Women

Steven C Moore  1 , Charles E Matthews  1 , Xiao Ou Shu  1 , Kai Yu  1 , Mitchell H Gail  1 , Xia Xu  1 , Bu-Tian Ji  1 , Wong-Ho Chow  1 , Qiuyin Cai  1 , Honglan Li  1 , Gong Yang  1 , David Ruggieri  1 , Jennifer Boyd-Morin  1 , Nathaniel Rothman  1 , Robert N Hoover  1 , Yu-Tang Gao  1 , Wei Zheng  1 , Regina G Ziegler  1
Affiliations

Endogenous Estrogens, Estrogen Metabolites, and Breast Cancer Risk in Postmenopausal Chinese Women

Steven C Moore et al. J Natl Cancer Inst. .

Abstract

Background: The role of estrogen metabolism in determining breast cancer risk and differences in breast cancer rates between high-incidence and low-incidence nations is poorly understood.

Methods: We measured urinary concentrations of estradiol and estrone (parent estrogens) and 13 estrogen metabolites formed by irreversible hydroxylation at the C-2, C-4, or C-16 positions of the steroid ring in a nested case-control study of 399 postmenopausal invasive breast cancer case participants and 399 matched control participants from the population-based Shanghai Women's Health Study cohort. Odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer by quartiles of metabolic pathway groups, pathway ratios, and individual estrogens/estrogen metabolites were estimated by multivariable conditional logistic regression. Urinary estrogen/estrogen metabolite measures were compared with those of postmenopausal non-hormone-using Asian Americans, a population with three-fold higher breast cancer incidence rates. All statistical tests were two-sided.

Results: Urinary concentrations of parent estrogens were strongly associated with breast cancer risk (ORQ4vsQ1 = 1.94, 95% CI = 1.21 to 3.12, Ptrend = .01). Of the pathway ratios, the 2-pathway:total estrogens/estrogen metabolites and 2-pathway:parent estrogens were inversely associated with risk (ORQ4vsQ1 = 0.57, 95% CI = 0.35 to 0.91, Ptrend = .03, and ORQ4vsQ1 = 0.61, 95% CI = 0.37 to 0.99, Ptrend = .04, respectively). After adjusting for parent estrogens, these associations remained clearly inverse but lost statistical significance (ORQ4vsQ1 = 0.65, 95% CI = 0.39 to 1.06, Ptrend = .12 and ORQ4vsQ1 = 0.76, 95% CI = 0.44 to 1.32, Ptrend = .28). The urinary concentration of all estrogens/estrogen metabolites combined in Asian American women was triple that in Shanghai women.

Conclusions: Lower urinary parent estrogen concentrations and more extensive 2-hydroxylation were each associated with reduced postmenopausal breast cancer risk in a low-risk nation. Markedly higher total estrogen/estrogen metabolite concentrations in postmenopausal United States women (Asian Americans) than in Shanghai women may partly explain higher breast cancer rates in the United States.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Pathways of estrogen metabolism. The parent estrogens estrone and estradiol can be irreversibly hydroxylated at the 2-, 4-, or 16-position of the steroid ring. The structures are for the unconjugated forms of estrogens and estrogen metabolites.
Figure 2.
Figure 2.
Median and interquartile range of urinary concentration of total estrogens/estrogen metabolites (pmol/mg creatinine) in postmenopausal women: Chinese women of Shanghai, Asian women of the United States, and US white women. Box plots above show the median ( middle line ) and interquartile range ( top and bottom lines ) of urinary concentrations of total estrogens/estrogen metabolites in five prior studies of postmenopausal women who were not using exogenous hormones. All five studies used the same estrogen metabolism assay, lab, and technician. Concentrations are not adjusted for age differences between populations, although age explained little variance in estrogen concentrations in our own data, possibly because all women were postmenopausal. Details for each study are as follows: 1) Chinese women from Shanghai: Concentrations based on the 399 control participants from the current study, with spot urines collected and kept on ice for a maximum of six hours until long term storage at -80 °C. 2) US white women from Colorado: Concentrations are based on 60 women from a random selection of Kaiser Permanente Colorado members (85% of whom were white), with spot urines collected and kept on ice for a maximum of 24 hours until long term storage at -80 °C ( 34 ). 3) Asian American women from California and Hawaii: Concentrations are based on 168 study control participants from San Francisco-Oakland CA, Los Angeles CA, or Oahu HI, with 12 hour overnight urines collected in a jug kept on ice for a maximum of 18 hours (from start of collection) until long term storage at -70 °C ( 4 ). 4) US white women from Maryland: Concentrations are based on 15 women, with overnight urines collected in a jug that was kept on ice until morning, then decanted, aliquoted, and frozen at -70 °C ( 35 ). 5) US white women from western New York state: Concentrations are based on 194 study control participants, 98% of whom were white, with first morning urines collected and kept on ice for approximately four hours until long term storage at -80 °C ( 36 ).
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Doll R, Payne P, Waterhouse J . Cancer Incidence in Five Continents , Vol. 1. Union Internationale Contre le Cancer, Geneva, Switzerland: : 1966. .
    1. Ferlay J, Soerjomataram I, Ervik M , et al. . GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide . IARC CancerBase No. 11. Lyon, France: : International Agency for Research on Cancer; . 2013. .
    1. Ziegler RG, Anderson WF, Gail MH . Increasing breast cancer incidence in China: the numbers add up . J Natl Cancer Inst . 2008. ; 100 ( 19 ): 1339 - 1341 . - PubMed
    1. Ziegler RG, Hoover RN, Pike MC , et al. . Migration patterns and breast cancer risk in Asian American women . J Natl Cancer Inst . 1993. ; 85 ( 22 ): 1819 - 1827 . - PubMed
    1. Gomez SL, Noone AM, Lichtensztajn DY , et al. . Cancer incidence trends among Asian American populations in the United States, 1990-2008 . J Natl Cancer Inst . 2013. ; 105 ( 15 ): 1096 - 1110 . - PMC - PubMed

Publication types