Independent and joint effects of serum 25-hydroxyvitamin D and calcium on ovarian cancer risk: A prospective nested case-control study

Introduction: 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. Conclusion: 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.