| Title: |
Circulating vitamin D concentrations and risk of breast and prostate cancer: a Mendelian randomization study. |
| Authors: |
Jiang, Xia; Dimou, Niki L; Al-Dabhani, Kawthar; Lewis, Sarah J; Martin, Richard M; Haycock, Philip C; Gunter, Marc J; Key, Timothy J; Eeles, Rosalind A; Muir, Kenneth; Neal, David; Giles, Graham G; Giovannucci, Edward L; Stampfer, Meir; Pierce, Brandon L; Schildkraut, Joellen M; Warren Andersen, Shaneda; Thompson, Deborah; Zheng, Wei; Kraft, Peter; Tsilidis, Konstantinos K; PRACTICAL, CRUK, BPC3, CAPS and PEGASUS consortia |
| Publisher Information: |
//doi.org/10.1093/ije/dyy284; Int J Epidemiol; Oxford University Press (OUP) |
| Publication Year: |
2019 |
| Collection: |
Apollo - University of Cambridge Repository |
| Subject Terms: |
Mendelian randomization; breast; malignancy; prostate; serum vitamin D concentrations; Aged; Breast Neoplasms; Causality; Female; Genome-Wide Association Study; Humans; Male; Mendelian Randomization Analysis; Middle Aged; Polymorphism; Single Nucleotide; Prostatic Neoplasms; Receptors; Estrogen; Risk Factors; Vitamin D |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
Print; application/pdf; application/msword |
| Language: |
English |
| Relation: |
https://www.repository.cam.ac.uk/handle/1810/275168 |
| DOI: |
10.17863/CAM.22346 |
| Availability: |
https://www.repository.cam.ac.uk/handle/1810/275168; https://doi.org/10.17863/CAM.22346 |
| Accession Number: |
edsbas.CCD8036D |
| Database: |
BASE |