title: Conditions associated with circulating tumor-associated folate receptor 1 protein in healthy men and women.
abstract: BACKGROUND
  Serum concentrations of the tumor-associated folate receptor 1 (FOLR1) protein may be a marker for early cancer detection, yet concentrations have also been detected in cancer-free women. We investigated the conditions associated with circulating FOLR1 protein in healthy individuals and sought to clarify the range of normal serum values.
  
  
  METHODS
  Sera of cancer-free men and women (N = 60) enrolled in a population-based cohort study in Alberta, Canada were analyzed for FOLR1 protein using an electrochemical luminescence immunoassay. Dietary, lifestyle, medical and reproductive history information was collected by questionnaires. Differences in serum FOLR1 concentrations between groups were assessed by non-parametric tests, and predictors of serum FOLR1 concentrations were estimated using multivariable linear regression.
  
  
  RESULTS
  Median serum FOLR1 concentration was higher in women (491 pg/ml, range = 327-693 pg/ml) than in men (404 pg/ml, range = 340-682 pg/ml), P = 0.001. FOLR1 concentration was also positively associated with vitamin A intake (P = 0.02), and showed positive trends with age and with oral contraceptive hormone use among women and an inverse trend with body mass index. All variables examined explained almost half of the variation in serum FOLR1 (model R2 = 0.44, P = 0.04); however, the retention of gender (P = 0.003) and vitamin A intake (P = 0.03) together explained 20% (P = 0.001) of serum FOLR1 variation. No other predictor was significant at P<0.05.
  
  
  CONCLUSIONS
  The positive association between serum FOLR1 concentration and female gender independent of an age effect suggests caution against statements to exploit serum FOLR1 for early cancer detection without further understanding the biological underpinnings of these observations. Serum FOLR1 concentrations may be influenced by the steroid retinoic acid (vitamin A) but do not appear to be associated with folate nutritional status. These findings require confirmation in larger independent studies.
authors.affiliation: Department of Population Health Research, Alberta Health Services, Calgary, Alberta, Canada; Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Linda E
authors.initials: LE
authors.lastname: Kelemen
authors.affiliation: Cancer Research United Kingdom Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom; Department of Oncology, University of Cambridge, Hutchison/Medical Research Council Research Centre, Cambridge, United Kingdom; National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, United Kingdom; Cambridge Experimental Cancer Medicine Centre, Cambridge, United Kingdom.
authors.forename: James D
authors.initials: JD
authors.lastname: Brenton
authors.affiliation: Cancer Research United Kingdom Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom.
authors.forename: Christine
authors.initials: C
authors.lastname: Parkinson
authors.affiliation: Cancer Research United Kingdom Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom; Department of Oncology, University of Cambridge, Hutchison/Medical Research Council Research Centre, Cambridge, United Kingdom.
authors.forename: Hayley
authors.initials: H
authors.lastname: C Whitaker
authors.affiliation: Cancer Research United Kingdom Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Piskorz
authors.affiliation: Department of Population Health Research, Alberta Health Services, Calgary, Alberta, Canada; Departments of Oncology and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Ilona
authors.initials: I
authors.lastname: Csizmadi
authors.affiliation: Alberta Health Services, Edmonton, Alberta, Canada; Department of Agricultural, Food and Nutritional Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Robson
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D004032:Diet; D005260:Female; D058975:Folate Receptor 1 / Q000097:blood*; D064368:Healthy Volunteers; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D012016:Reference Values; D012098:Reproduction
chemical_list: C548696:FOLR1 protein, human; D058975:Folate Receptor 1