Originally published as JCO Early Release 10.1200/JCO.2007.13.9964 on March 3 2008

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Plasma Isoflavone Level and Subsequent Risk of Breast Cancer Among Japanese Women: A Nested Case-Control Study From the Japan Public Health Center-Based Prospective Study Group

Motoki Iwasaki, Manami Inoue, Tetsuya Otani, Shizuka Sasazuki, Norie Kurahashi, Tsutomu Miura, Seiichiro Yamamoto, Shoichiro Tsugane

From the Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center; Department of Sport and Exercise Nutrition, School of Physical Education, Sendai University; and the Cancer Information Services and Surveillance Division, Center for Cancer Control and Information Services, National Cancer Center, Tokyo, Japan

Corresponding author: Motoki Iwasaki, MD, PhD, Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan; e-mail: moiwasak{at}gan2.res.ncc.go.jp

Purpose Because they have large variations in consumption, Asian countries are suitable settings for studies of the effect of relatively high-dose isoflavone intake on breast cancer risk. Nevertheless, no prospective study from Asia has assessed blood or urine levels as biomarkers of isoflavone intake.

Patients and Methods A total of 24,226 women ages 40 to 69 years in the Japan Public Health Center–based prospective study who responded to the baseline questionnaire and provided blood in 1990 to 1995 were observed to December 2002. During a mean 10.6 years of follow-up, 144 patients newly diagnosed with breast cancer were identified. Two matched controls for each patient were selected from the cohort. Isoflavone levels were assessed by plasma level and food frequency questionnaire, and the odds ratio of breast cancer according to isoflavone level was estimated using a conditional logistic regression model.

Results We found a statistically significant inverse association between plasma genistein and risk of breast cancer, but no association for plasma daidzein. Adjusted odds ratios for the highest versus lowest quartile of plasma level were 0.34 for genistein (95% CI, 0.16 to 0.74; P for trend, .02) and 0.71 for daidzein (95% CI, 0.35 to 1.44; P for trend, .54). Median plasma genistein values in the control group were 31.9 ng/mL for the lowest and 353.9 ng/mL for the highest quartile groups. Regarding dietary intake of isoflavones, nonsignificant inverse associations were observed for both genistein and daidzein.

Conclusion This nested case-control study found an inverse association between plasma genistein and the risk of breast cancer in Japan.

published online ahead of print at www.jco.org on March 3, 2008.

Supported by grants-in-aid for cancer research, for the Third Term Comprehensive Ten-Year Strategy for Cancer Control, and for Research on Risk of Chemical Substances from the Ministry of Health, Labour, and Welfare of Japan; and Grant-In-Aid No. 17015049 for Scientific Research on Priority Areas and Grant-In-Aid No. 17790378 for Young Scientists from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and Japan Society for the Promotion of Science.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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