TY - JOUR
T1 - Enterolactone is differently associated with estrogen receptor beta-negative and -positive breast cancer in a Swedish nested case-control study
AU - Sonestedt, Emily
AU - Borgquist, Signe
AU - Ericson, Ulrika
AU - Gullberg, Bo
AU - Olsson, Håkan
AU - Adlercreutz, Herman
AU - Landberg, Göran
AU - Wirfält, Elisabet
PY - 2008/11
Y1 - 2008/11
N2 - 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 ERbeta-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 ERalpha and ERbeta 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 ERalpha [positive (+); odds ratio, 0.73; 95% CI, 0.55-0.97] and ERbeta [negative (-)] tumors (odds ratio, 0.60; 95% CI, 0.42-0.84), with significantly different risks for ERbeta (-) and ERbeta (+) 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 ERbeta (-) and ERbeta (+) tumors and most evident in tumors that express ERalpha but not ERbeta.
AB - 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 ERbeta-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 ERalpha and ERbeta 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 ERalpha [positive (+); odds ratio, 0.73; 95% CI, 0.55-0.97] and ERbeta [negative (-)] tumors (odds ratio, 0.60; 95% CI, 0.42-0.84), with significantly different risks for ERbeta (-) and ERbeta (+) 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 ERbeta (-) and ERbeta (+) tumors and most evident in tumors that express ERalpha but not ERbeta.
KW - 4-Butyrolactone/analogs & derivatives
KW - Adult
KW - Aged
KW - Biomarkers, Tumor/metabolism
KW - Breast Neoplasms/metabolism
KW - Case-Control Studies
KW - Diet
KW - Estrogen Receptor alpha/metabolism
KW - Estrogen Receptor beta/metabolism
KW - Female
KW - Humans
KW - Lignans/metabolism
KW - Linear Models
KW - Microarray Analysis
KW - Middle Aged
KW - Obesity/metabolism
KW - Prospective Studies
KW - Reproducibility of Results
KW - Risk Assessment
KW - Smoking/metabolism
KW - Surveys and Questionnaires
KW - Sweden/epidemiology
U2 - 10.1158/1055-9965.EPI-08-0393
DO - 10.1158/1055-9965.EPI-08-0393
M3 - Article
C2 - 18990767
SN - 1055-9965
VL - 17
SP - 3241
EP - 3251
JO - Cancer Epidemiology, Biomarkers and Prevention
JF - Cancer Epidemiology, Biomarkers and Prevention
IS - 11
ER -