Title |
Circulating Selenium and Prostate Cancer Risk: A Mendelian Randomization Analysis
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Published in |
JNCI: Journal of the National Cancer Institute, May 2018
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DOI | 10.1093/jnci/djy081 |
Pubmed ID | |
Authors |
James Yarmolinsky, Carolina Bonilla, Philip C Haycock, Ryan J Q Langdon, Luca A Lotta, Claudia Langenberg, Caroline L Relton, Sarah J Lewis, David M Evans, PRACTICAL Consortium, George Davey Smith, Richard M Martin |
Abstract |
In the Selenium and Vitamin E Cancer Prevention Trial (SELECT), selenium supplementation (causing a median 114 μg/L increase in circulating selenium) did not lower overall prostate cancer risk, but increased risk of high-grade prostate cancer and type 2 diabetes. Mendelian randomization analysis uses genetic variants to proxy modifiable risk factors and can strengthen causal inference in observational studies. We constructed a genetic instrument comprising 11 single nucleotide polymorphisms robustly (P < 5 × 10-8) associated with circulating selenium in genome-wide association studies. In a Mendelian randomization analysis of 72 729 men in the PRACTICAL Consortium (44 825 case subjects, 27 904 control subjects), 114 μg/L higher genetically elevated circulating selenium was not associated with prostate cancer (odds ratio [OR] = 1.01, 95% confidence interval [CI] = 0.89 to 1.13). In concordance with findings from SELECT, selenium was weakly associated with advanced (including high-grade) prostate cancer (OR = 1.21, 95% CI = 0.98 to 1.49) and type 2 diabetes (OR = 1.18, 95% CI = 0.97 to 1.43; in a type 2 diabetes genome-wide association study meta-analysis with up to 49 266 case subjects and 249 906 control subjects). Our Mendelian randomization analyses do not support a role for selenium supplementation in prostate cancer prevention and suggest that supplementation could have adverse effects on risks of advanced prostate cancer and type 2 diabetes. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 7 | 33% |
United States | 2 | 10% |
Netherlands | 1 | 5% |
France | 1 | 5% |
Chile | 1 | 5% |
Norway | 1 | 5% |
Unknown | 8 | 38% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 15 | 71% |
Scientists | 4 | 19% |
Science communicators (journalists, bloggers, editors) | 1 | 5% |
Practitioners (doctors, other healthcare professionals) | 1 | 5% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 95 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 17 | 18% |
Student > Ph. D. Student | 14 | 15% |
Student > Master | 9 | 9% |
Student > Doctoral Student | 5 | 5% |
Student > Bachelor | 5 | 5% |
Other | 16 | 17% |
Unknown | 29 | 31% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 19 | 20% |
Biochemistry, Genetics and Molecular Biology | 13 | 14% |
Agricultural and Biological Sciences | 8 | 8% |
Nursing and Health Professions | 4 | 4% |
Computer Science | 3 | 3% |
Other | 10 | 11% |
Unknown | 38 | 40% |