Urinary Phytoestrogen Excretion and Breast Cancer Risk

Urinary Phytoestrogen Excretion and Breast Cancer Risk

Evaluating Potential Effect Modifiers Endogenous Estrogens and Anthropometrics1

Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37232-8300 [Q. D., X-o. S., W. Z.]; Cancer Research Center of Hawaii, Honolulu, Hawaii 96813 [A. A. F., L. J. C.]; Department of Epidemiology and Public Health, Yale School of Medicine, New Haven, Connecticut 06520 [H. Y.]; Department of Epidemiology, Shanghai Cancer Institute, Shanghai 200032, People’s Republic of China [F. J., Y-T. G.]; and Department of Epidemiology and Biostatistics, Norman J. Arnold School of Public Health, University of South Carolina, Columbia, South Carolina 29203 [J. R. H.]

Abstract

Steroid sex hormones play a central role in breast carcinogenesis. Evidence from in vitro and animal studies suggests that phytoestrogens may inhibit the development of mammary tumors through their role in regulating the synthesis, metabolism, and signal transduction of steroid hormones. In a study of 117 case-control pairs of postmenopausal women in Shanghai, we investigated whether the association between urinary phytoestrogen excretion and breast cancer risk may differ by levels of endogenous steroid sex hormones, sex hormone binding globulin (SHBG), body mass index (BMI), and waist:hip ratio (WHR). Fasting morning blood and urine samples were collected for the analysis of urinary isoflavonoids and mammalian lignans, as well as blood levels of SHBG and selected steroid hormones. For cancer patients, samples were collected before any cancer therapy. Conditional logistic regression models were used to estimate odds ratios and 95% confidence intervals after adjusting for potential confounding factors. The inverse associations between urinary phytoestrogens and breast cancer risk were found to be more evident among women with a high BMI or WHR than those with a low level of these anthropometric measurements. Although a reduced risk of breast cancer was observed among women with a high excretion rate of urinary isoflavonoids in all of the strata defined by blood SHBG and steroid hormones, the inverse association was more pronounced among women with a high blood concentration of estradiol, a low level of estrone sulfate, or a low level of SHBG. The risks of breast cancer were also reduced with increasing excretion rate of mammalian lignans, although no test for a linear association was statistically significant in stratified analyses. Findings from this study suggest that the potential protective association of phytoestrogens may be modified by BMI, WHR, and blood levels of SHBG, and steroid hormones.

Footnotes

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↵1 This work was supported by USPHS Grants R01 CA64277, RO3 CA90990, RO3 CA83050, and CA71789 for supplemental Cancer Center Support Grant support of liquid chromatography/mass spectrometry equipment.
↵2 To whom requests for reprints should be addressed, at Vanderbilt University Medical Center, Health Services Research, Medical Center East, Suite 6000, Nashville, TN 37232-8300. Phone: (615) 936-0682; Fax: (615) 936-1269; E-mail: wei.zheng{at}mcmail.vanderbilt.edu
↵3 The abbreviations used are: E₂, estradiol; 17β-HSD1, 17β-hydroxysteroid dehydrogenase type 1; SHBG, sex hormone-binding globulin; BMI, body mass index; WHR, waist:hip ratio; O-DMA, o-desmethylangolensin; CV, coefficient of variation; E₁, estrone; E₁-S, estrone sulfate; DHEA-S, dehydroepiandrosterone sulfate; OR, odds ratio; CI, confidence interval.
- Accepted March 18, 1903.
- Received July 5, 1902.
- Revision received March 10, 1903.