title: Vitamin D, PTH, and calcium and tumor aggressiveness in prostate cancer: a prospective nested case-control study.
abstract: OBJECTIVE
  Epidemiological studies suggest that low levels of vitamin D (25OHD) constitute a risk factor for more aggressive prostate cancer. We examined the relationship between pre-diagnostic serum levels of vitamin D, parathyroid hormone (PTH), and calcium and risk of prostate cancer according to tumor aggressiveness.
  
  
  METHODS
  We performed a nested case-control study within the Malmö Diet and Cancer Study on 943 incident prostate cancer cases. Tumor aggressiveness was defined by Gleason score, TNM stage, and serum levels of total prostate-specific antigen. Odds ratios (OR) were calculated for different quartiles of serum levels of 25OHD, PTH, and calcium, and for interactions between them.
  
  
  RESULTS
  We found no significant association when comparing aggressive to non-aggressive disease regarding vitamin D, PTH, or calcium. There was a trend toward an increased risk in low-grade tumors, i.e., Gleason score ≤6, and a significant association regarding Gleason score 7 tumors with OR 1.70 (1.09-2.65) in the highest quartile of vitamin D. Stratifying the analysis yielded several significant findings demonstrating a nonspecific interaction between the metabolites. In men with PTH above median, the risk of aggressive prostate cancer was double in the highest vitamin D quartile, OR 2.01 (1.24-3.25), and for non-aggressive cancer 1.82 (1.25-2.66). There was an inverse effect on risk of prostate cancer in men with PTH above median and vitamin D ≤50 nmol/L, OR 0.25 (0.09-0.71) and calcium ≤2.37 mmol/L, OR 0.53 (0.34-0.82) for aggressive cancer.
  
  
  CONCLUSIONS
  This study showed no significant association when comparing aggressive to non-aggressive disease. There was a possible relationship between vitamin D and low-risk tumors. There were both positive and negative interactions between PTH, calcium, and vitamin D and risk of prostate cancer. These results were similar for low-risk and aggressive cases.
authors.affiliation: Department of Urology, Skåne University Hospital Malmö, Lund University, 205 02, Malmö, Sweden. johan.brandstedt@skane.se.
authors.forename: Johan
authors.initials: J
authors.lastname: Brändstedt
authors.affiliation: Department of Surgery, Skåne University Hospital Lund, Lund University, Malmö, Sweden.|Department of Surgery, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Almquist
authors.affiliation: Department of Urology, Skåne University Hospital Malmö, Lund University, 205 02, Malmö, Sweden.|Department of Translational Medicine in Malmö, Skåne University Hospital, Lund University, Malmö, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Ulmert
authors.affiliation: Department of Plastic Surgery, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.|Department of Surgery, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Manjer
authors.affiliation: Department of Laboratory Medicine, Section for Clinical Chemistry, Skåne University Hospital, Malmö, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Malm
mesh_terms: D000368:Aged; D002118:Calcium / Q000097:blood*; D016022:Case-Control Studies; D004032:Diet; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D010281:Parathyroid Hormone / Q000097:blood*; D011446:Prospective Studies; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology*; D014807:Vitamin D / Q000097:blood*
chemical_list: D010281:Parathyroid Hormone; D014807:Vitamin D; D017430:Prostate-Specific Antigen; D002118:Calcium
keywords: Calcium; PTH; Prostate cancer; Tumor aggressiveness; Vitamin D