Purpose: 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.
Keywords: Calcium; PTH; Prostate cancer; Tumor aggressiveness; Vitamin D.