Enterolactone Is Differently Associated with Estrogen Receptor β–Negative and –Positive Breast Cancer in a Swedish Nested Case-Control Study

doi:10.1158/1055-9965.EPI-08-0393

Enterolactone Is Differently Associated with Estrogen Receptor β–Negative and –Positive Breast Cancer in a Swedish Nested Case-Control Study

¹Department of Clinical Sciences in Malmö and ²Department of Laboratory Medicine, Center for Molecular Pathology, Lund University, Malmö, Sweden; ³Department of Clinical Sciences in Lund, Lund University, Lund, Sweden; and ⁴Institute for Preventive Medicine, Nutrition and Cancer, Folkhälsan Research Center, and Division of Clinical Chemistry, University of Helsinki, Helsinki, Finland

Requests for reprints:
Emily Sonestedt, Research Group in Nutrition Epidemiology, Department of Clinical Sciences in Malmö, Lund University, Malmo University Hospital, Cancer Research Centre Entrance 72, Building 60 Floor 13, SE-205 02 Malmö, Sweden. Phone: 46-40-39-13-24; Fax: 46-40-39-13-22. E-mail: Emily.Sonestedt{at}med.lu.se

Abstract

Background: Differences in the estrogen receptor (ER) status of tumors may explain ambiguities in epidemiologic studies between the blood concentrations of enterolactone and breast cancer. To our knowledge, the association between enterolactone and ERβ-defined breast cancer has previously not been examined.

Methods: A nested case-control study within the Malmö Diet and Cancer cohort used 366 cases and 733 matched controls to identify the major determinants of plasma enterolactone and to examine the association between enterolactone concentration and breast cancer risk and if this association differs depending on the ERα and ERβ status of tumors. A modified diet history method assessed dietary habits. Time-resolved fluoroimmunoassay determined enterolactone concentrations and immunohistochemistry using tissue microarray determined ER status.

Results: Dietary fiber, as well as fruits and berries, and high-fiber bread showed statistically significant correlations with enterolactone (r, 0.13-0.22). Smoking and obesity were associated with lower enterolactone concentrations. Enterolactone concentrations above the median (16 nmol/L) were associated with reduced breast cancer risk when compared with those below [odds ratio, 0.75; 95% confidence interval (95% CI), 0.58-0.98]. The reduced risk was only observed for ERα [positive (+); odds ratio, 0.73; 95% CI, 0.55-0.97] and ERβ [negative (−)] tumors (odds ratio, 0.60; 95% CI, 0.42-0.84), with significantly different risks for ERβ (−) and ERβ (+) tumors (P for heterogeneity = 0.04).

Conclusions: This study supports the suggestion that enterolactone is a biomarker of a healthy lifestyle. The protective association between enterolactone and breast cancer was significantly different between ERβ (−) and ERβ (+) tumors and most evident in tumors that express ERα but not ERβ. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3241–51)

Footnotes

Grant support: Swedish Research Council (grant K2006-27X-20060-01-3), Swedish Council for Working and Social Research (grant 2005-0251), Swedish Cancer Society (grant 4886-B03-01XAB), Swedish Research Council Formas (grant 222-2005-1833), and Swedish Nutrition Foundation.
- Accepted August 20, 2008.
- Received April 30, 2008.
- Revision received August 7, 2008.