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

Jue-Sheng Ong; Suzanne C Dixon-Suen; Xikun Han; Jiyuan An; Esophageal Cancer Consortium; 23 and Me Research Team; Upekha Liyanage; Jean-Cluade Dusingize; Johannes Schumacher; Ines Gockel; Anne Böhmer; Janusz Jankowski; Claire Palles; Tracy O'Mara; Amanda Spurdle; Matthew H Law; Mark M Iles; Paul Pharoah; Andrew Berchuck; Wei Zheng; Aaron P Thrift; Catherine Olsen; Rachel E Neale; Puya Gharahkhani; Penelope M Webb; Stuart MacGregor

doi:10.1038/s41467-020-20368-w

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

Nat Commun. 2021 Jan 11;12(1):246. doi: 10.1038/s41467-020-20368-w.

Authors

Jue-Sheng Ong¹, Suzanne C Dixon-Suen², Xikun Han^{3

4}, Jiyuan An⁵; Esophageal Cancer Consortium; 23 and Me Research Team; Upekha Liyanage⁶, Jean-Cluade Dusingize⁷, Johannes Schumacher⁸, Ines Gockel⁹, Anne Böhmer¹⁰, Janusz Jankowski^{11

12}, Claire Palles¹³, Tracy O'Mara¹⁴, Amanda Spurdle¹⁴, Matthew H Law³, Mark M Iles¹⁵, Paul Pharoah¹⁶, Andrew Berchuck¹⁷, Wei Zheng¹⁸, Aaron P Thrift¹⁹, Catherine Olsen^{4

7}, Rachel E Neale²⁰, Puya Gharahkhani³, Penelope M Webb²¹, Stuart MacGregor³

Affiliations

¹ Statistical Genetics Group, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD, 4006, Australia. juesheng.ong@qimrberghofer.edu.au.
² Cancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Rd, Melbourne, VIC, 3004, Australia.
³ Statistical Genetics Group, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD, 4006, Australia.
⁴ Faculty of Medicine, University of Queensland, Brisbane, Australia.
⁵ Institute for Future Environments, Queensland University of Technology, QLD, Brisbane, QLD, 4001, Australia.
⁶ Cancer and Population Studies Group, Population Health Department, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD, 4006, Australia.
⁷ Cancer Control Group, Population Health Department, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD, Australia.
⁸ Institute of Human Genetics, Philipps University of Marburg, Marburg, Germany.
⁹ Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany.
¹⁰ Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
¹¹ Centre for Medicine and Health Sciences, University of Arab Emirates University, Abu Dhabi, UAE.
¹² Comprehensive Clinical Trials Unit, University College London, London, UK.
¹³ Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, UK.
¹⁴ Molecular Cancer Epidemiology Group, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD, Australia.
¹⁵ Leeds Institute for Data Analytics, University of Leeds, Leeds, UK.
¹⁶ Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
¹⁷ Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Box 3079, Durham, NC, 27710, USA.
¹⁸ Division of Epidemiology, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
¹⁹ Section of Epidemiology and Population Sciences, Department of Medicine, and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
²⁰ Cancer Aetiology and Prevention Group, Population Health Department, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD, Australia.
²¹ Gynaecological Cancer Group, Population Health Department, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD, Australia.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Case-Control Studies
Child
Genetic Predisposition to Disease*
Humans
Mendelian Randomization Analysis*
Multivariate Analysis
Neoplasms / genetics*
Pigmentation / genetics
Risk Factors
Sunburn / genetics
Vitamin D / metabolism*

Substances

Vitamin D

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

Authors

Collaborators

Affiliations

Abstract

Publication types

MeSH terms

Substances

Grants and funding