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

European Journal of Clinical Nutrition volume 75, pages 417–429 (2021)Cite this article

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Abstract

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.

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Fig. 1
Fig. 2: Association between total calcium intake and serum calcium and ovarian cancer risk.
Fig. 3: Association between total vitamin D intake and serum 25(OH)D and ovarian cancer risk.
Fig. 4: Dose-response relationship between total calcium intake and dietary calcium intake and ovarian cancer risk. (Conducted by using cohort studies).

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Acknowledgements

This work was supported by Zhejiang Provincial Natural Science Foundation of China (NO.LY18C060001), the National Natural Science Foundation of China (Grant No: 21976155, 81773016, and 31471297).

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  1. These authors contributed equally: Jiawei Xu, Kelie Chen, Fan Zhao

Authors and Affiliations

  1. Department of Toxicology of School of Public Health, and Department of Gynecologic Oncology of Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China

    Jiawei Xu, Kelie Chen, Hui Lin, Yihua Wu & Dajing Xia

  2. Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, 310058, China

    Fan Zhao, Yongfeng Wu & Yexinyi Zhou

  3. Department of Pathology, Key Laboratory of Disease Proteomics of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, 310058, China

    Dongdong Huang & Honghe Zhang

  4. Department of Gynecological Oncology, Zhejiang Cancer Hospital, Hangzhou, 310022, China

    Zhiqin Fu

  5. Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China

    Jinming Xu & Yongfeng Wu

  6. Department of Gynecologic Oncology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, China

    Weiguo Lu

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Contributions

The authors’ responsibilities were as follows: Jiawei Xu, Kelie Chen, and Fan Zhao contributed equally to this work; Dajing Xia and Yihua Wu contributed to conception and design of the study, and had the right to grant on behalf of all authors; Jiawei Xu, Kelie Chen, and Fan Zhao contributed to design, identifying and acquiring reports of studies, extracting data, analyzing data and drafting the manuscript; Yongfeng Wu, Jinming Xu, Dongdong Huang, Zhiqin Fu, Yexinyi Zhou, Honghe Zhang, and Hui Lin provided statistical advice and assistance in data interpretation; Weiguo Lu polished the manuscript and all authors read and approved the final manuscript.

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Xu, J., Chen, K., Zhao, F. et al. Association between vitamin D/calcium intake and 25-hydroxyvitamin D and risk of ovarian cancer: a dose-response relationship meta-analysis. Eur J Clin Nutr 75, 417–429 (2021). https://doi.org/10.1038/s41430-020-00724-1

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