title: Independent and joint effects of serum 25-hydroxyvitamin D and calcium on ovarian cancer risk: a prospective nested case-control study.
abstract: BACKGROUND
  Ovarian cancer has very few known modifiable risk factors but dietary studies suggest a role for vitamin D and calcium in the prevention of ovarian cancer. Thus, we investigated the association between pre-diagnostic serum calcium and 25-hydroxyvitamin D (25-OHD) on the risk of later development of ovarian cancer.
  
  
  METHODS
  We conducted a population-based nested case-control study within the Finnish Maternity Cohort (FMC). The cohort subset comprised 172 ovarian cancer cases with 172 matched controls (age ± 1 year, parity and season of blood donation ± 2 weeks).
  
  
  RESULTS
  We observed a significant inverse association between calcium and ovarian cancer risk. Relative risk (estimated as odds ratio, OR) comparing the highest quartile to the lowest quartile was significantly decreased; 0.41 [95% confidence interval (CI) 0.19-0.85, P-trend 0.004]. Even though a comparable association between 25-OHD and ovarian cancer did not reach statistical significance (OR 0.57, 95% CI 0.26-1.24, P-trend 0.07), having sufficient (> 75 nmol/L) serum 25-OHD levels compared to insufficient serum 25-OHD was associated with a significantly decreased risk of ovarian cancer (OR 0.32; 95% CI 0.12-0.91, p-value 0.03). No synergistic protective interaction between high levels of calcium and 25-OHD against ovarian cancer was observed, the joint effect being just multiplicative.
  
  
  CONCLUSIONS
  Calcium and vitamin D act independently to reduce the risk of ovarian cancer. The decreased risk of ovarian cancer associated with pre-diagnostic serum calcium and vitamin D needs to be evaluated further for possible new insights into ovarian cancer prevention.
authors.affiliation: National Institute for Health and Welfare, Finland. Adetunji.toriola@uta.fi
authors.forename: Adetunji T
authors.initials: AT
authors.lastname: Toriola
authors.forename: Helja-Marja
authors.initials: HM
authors.lastname: Surcel
authors.forename: Agborsangaya
authors.initials: A
authors.lastname: Calypse
authors.forename: Kjell
authors.initials: K
authors.lastname: Grankvist
authors.forename: Tapio
authors.initials: T
authors.lastname: Luostarinen
authors.forename: Annekatrin
authors.initials: A
authors.lastname: Lukanova
authors.forename: Eero
authors.initials: E
authors.lastname: Pukkala
authors.forename: Matti
authors.initials: M
authors.lastname: Lehtinen
mesh_terms: D000328:Adult; D002118:Calcium / Q000378:metabolism*; D016022:Case-Control Studies; D004357:Drug Synergism; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000097:blood* / Q000209:etiology; D011446:Prospective Studies; D012307:Risk Factors; D012621:Seasons; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D; D002118:Calcium