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A comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization

Author

Listed:
  • Jue-Sheng Ong

    (QIMR Berghofer Medical Research Institute)

  • Suzanne C. Dixon-Suen

    (Cancer Council Victoria)

  • Xikun Han

    (QIMR Berghofer Medical Research Institute
    University of Queensland)

  • Jiyuan An

    (Queensland University of Technology, QLD)

  • Upekha Liyanage

    (QIMR Berghofer Medical Research Institute)

  • Jean-Cluade Dusingize

    (QIMR Berghofer Medical Research Institute)

  • Johannes Schumacher

    (Philipps University of Marburg)

  • Ines Gockel

    (University Hospital Leipzig)

  • Anne Böhmer

    (University of Bonn, School of Medicine & University Hospital Bonn)

  • Janusz Jankowski

    (University of Arab Emirates University
    University College London)

  • Claire Palles

    (University of Birmingham)

  • Tracy O’Mara

    (QIMR Berghofer Medical Research Institute)

  • Amanda Spurdle

    (QIMR Berghofer Medical Research Institute)

  • Matthew H. Law

    (QIMR Berghofer Medical Research Institute)

  • Mark M. Iles

    (University of Leeds)

  • Paul Pharoah

    (University of Cambridge)

  • Andrew Berchuck

    (Division of Gynecologic Oncology, Duke University Medical Center)

  • Wei Zheng

    (Vanderbilt University School of Medicine)

  • Aaron P. Thrift

    (Baylor College of Medicine)

  • Catherine Olsen

    (University of Queensland
    QIMR Berghofer Medical Research Institute)

  • Rachel E. Neale

    (QIMR Berghofer Medical Research Institute)

  • Puya Gharahkhani

    (QIMR Berghofer Medical Research Institute)

  • Penelope M. Webb

    (QIMR Berghofer Medical Research Institute)

  • Stuart MacGregor

    (QIMR Berghofer Medical Research Institute)

Abstract

Previous Mendelian randomization (MR) studies on 25-hydroxyvitamin D (25(OH)D) and cancer have typically adopted a handful of variants and found no relationship between 25(OH)D and cancer; however, issues of horizontal pleiotropy cannot be reliably addressed. Using a larger set of variants associated with 25(OH)D (74 SNPs, up from 6 previously), we perform a unified MR analysis to re-evaluate the relationship between 25(OH)D and ten cancers. Our findings are broadly consistent with previous MR studies indicating no relationship, apart from ovarian cancers (OR 0.89; 95% C.I: 0.82 to 0.96 per 1 SD change in 25(OH)D concentration) and basal cell carcinoma (OR 1.16; 95% C.I.: 1.04 to 1.28). However, after adjustment for pigmentation related variables in a multivariable MR framework, the BCC findings were attenuated. Here we report that lower 25(OH)D is unlikely to be a causal risk factor for most cancers, with our study providing more precise confidence intervals than previously possible.

Suggested Citation

  • Jue-Sheng Ong & Suzanne C. Dixon-Suen & Xikun Han & Jiyuan An & Upekha Liyanage & Jean-Cluade Dusingize & Johannes Schumacher & Ines Gockel & Anne Böhmer & Janusz Jankowski & Claire Palles & Tracy O’M, 2021. "A comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20368-w
    DOI: 10.1038/s41467-020-20368-w
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