title: Enterolactone is differently associated with estrogen receptor beta-negative and -positive breast cancer in a Swedish nested case-control study.
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 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.
authors.affiliation: Department of Clinical Sciences in Malmö, Research Group in Nutrition Epidemiology, Lund University, Malmo University Hospital, Cancer Research Centre Entrance 72, Building 60 Floor 13, SE-205 02 Malmö, Sweden. Emily.Sonestedt@med.lu.se
authors.forename: Emily
authors.initials: E
authors.lastname: Sonestedt
authors.forename: Signe
authors.initials: S
authors.lastname: Borgquist
authors.forename: Ulrika
authors.initials: U
authors.lastname: Ericson
authors.forename: Bo
authors.initials: B
authors.lastname: Gullberg
authors.forename: Håkan
authors.initials: H
authors.lastname: Olsson
authors.forename: Herman
authors.initials: H
authors.lastname: Adlercreutz
authors.forename: Göran
authors.initials: G
authors.lastname: Landberg
authors.forename: Elisabet
authors.initials: E
authors.lastname: Wirfält
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000378:metabolism; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D016022:Case-Control Studies; D004032:Diet; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D006801:Humans; D017705:Lignans / Q000378:metabolism*; D016014:Linear Models; D046228:Microarray Analysis; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism; D011446:Prospective Studies; D015203:Reproducibility of Results; D018570:Risk Assessment; D012907:Smoking / Q000378:metabolism; D011795:Surveys and Questionnaires; D013548:Sweden / Q000453:epidemiology
chemical_list: D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D017705:Lignans; D015107:4-Butyrolactone; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone