Format

Send to

Choose Destination
Int J Epidemiol. 2018 Dec 28. doi: 10.1093/ije/dyy284. [Epub ahead of print]

Circulating vitamin D concentrations and risk of breast and prostate cancer: a Mendelian randomization study.

Author information

1
Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
2
Cardiovascular Epidemiology Unit, Department of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
3
Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece.
4
Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, UK.
5
Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
6
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
7
National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK.
8
Nutritional Epidemiology Group, Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France.
9
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
10
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
11
Institute of Cancer Research, Royal Marsden NHS Foundation Trust, London, UK.
12
Institute of Population Health, University of Manchester, Manchester, UK.
13
Nuffield Department of Surgery, University of Oxford, Oxford, UK.
14
Department of Oncology, University of Cambridge, Cambridge, UK.
15
Cancer Epidemiology & Intelligence Division, Cancer Council Victoria, Melbourne, VIC, Australia.
16
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
17
Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
18
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
19
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
20
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
21
Department of Public Health Sciences, The University of Chicago, Chicago, IL, USA.
22
Department of Human Genetics, Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA.
23
Department of Human Genetics, The University of Chicago, Chicago, IL, USA.
24
Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
25
Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
26
Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, UK.
27
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.

Abstract

Background:

Observational studies have suggested an association between circulating vitamin D concentrations [25(OH)D] and risk of breast and prostate cancer, which was not supported by a recent Mendelian randomization (MR) analysis comprising 15 748 breast and 22 898 prostate-cancer cases. Demonstrating causality has proven challenging and one common limitation of MR studies is insufficient power.

Methods:

We aimed to determine whether circulating concentrations of vitamin D are causally associated with the risk of breast and prostate cancer, by using summary-level data from the largest ever genome-wide association studies conducted on vitamin D (N = 73 699), breast cancer (Ncase = 122 977) and prostate cancer (Ncase = 79 148). We constructed a stronger instrument using six common genetic variants (compared with the previous four variants) and applied several two-sample MR methods.

Results:

We found no evidence to support a causal association between 25(OH)D and risk of breast cancer [OR per 25 nmol/L increase, 1.02 (95% confidence interval: 0.97-1.08), P = 0.47], oestrogen receptor (ER)+ [1.00 (0.94-1.07), P = 0.99] or ER- [1.02 (0.90-1.16), P = 0.75] subsets, prostate cancer [1.00 (0.93-1.07), P = 0.99] or the advanced subtype [1.02 (0.90-1.16), P = 0.72] using the inverse-variance-weighted method. Sensitivity analyses did not reveal any sign of directional pleiotropy.

Conclusions:

Despite its almost five-fold augmented sample size and substantially improved statistical power, our MR analysis does not support a causal effect of circulating 25(OH)D concentrations on breast- or prostate-cancer risk. However, we can still not exclude a modest or non-linear effect of vitamin D. Future studies may be designed to understand the effect of vitamin D in subpopulations with a profound deficiency.

PMID:
30597039
DOI:
10.1093/ije/dyy284

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center