Association between vitamin D/calcium intake and 25-hydroxyvitamin D and risk of ovarian cancer: a dose-response relationship meta-analysis

Background: The association between vitamin D/calcium and risk of ovarian cancer is still a debatable point. The aim of our study was to systematically investigate the association between vitamin D/calcium, and the risk of ovarian cancer and estimate their dose-response association quantitatively. Methods: PubMed, EMBASE, and Web of Science databases were searched to identify relevant observational studies. Two investigators screened citations and extracted data independently. Data were extracted and the association between vitamin D/calcium and ovarian cancer risk was estimated by calculating pooled relative risks (RRs). Subgroup analyses, publication bias estimation, and dose-response analyses were carried out as well. Results: In total, 21 articles involving 980,008 participants were included in our present study. No significant association was observed between total vitamin D intake and ovarian cancer risk (RR: 1.02; 95% CI, 0.89–1.16, p= 0.81). Further subgroup analysis suggested that neither dietary vitamin D intake (RR: 0.80; 95% CI, 0.62–1.03, p= 0.09) nor supplementary vitamin D intake (RR: 0.98; 95% CI, 0.85–1.13, p= 0.80) was associated with the risk of ovarian cancer. As for calcium, total calcium intake was found to be statistically inversely associated with ovarian cancer risk in case–control studies (RR: 0.73; 95% CI, 0.63–0.86, p< 0.001) but not in cohort studies (RR: 1.05; 95% CI, 0.90–1.24, p= 0.52). Besides, supplementation with calcium plus vitamin D was not effective for the prevention of ovarian cancer (p= 0.98). Of note, dose-response analysis based on cohort studies suggested a potential inverse U-shape relationship between calcium intake (including total calcium and dietary calcium) and ovarian cancer risk, which indicated that low dose of calcium intake might reduce ovarian cancer risk while high dose of calcium intake might not. Conclusions: Taken together, vitamin D could not decrease the risk of ovarian cancer. The role of calcium intake was not proven for reducing ovarian cancer risk. Besides, no evidence showed combinative use of calcium and vitamin D have additional benefits for ovarian cancer prevention.