RT Journal Article
SR Electronic
T1 Circulating selenium and prostate cancer risk: a Mendelian randomization analysis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 223248
DO 10.1101/223248
A1 Yarmolinsky, James
A1 Bonilla, Carolina
A1 Haycock, Philip C
A1 Langdon, Ryan JQ
A1 Lotta, Luca A
A1 Langenberg, Claudia
A1 Relton, Caroline L
A1 Lewis, Sarah J
A1 Evans, David M
A1 ,
A1 Smith, George Davey
A1 Martin, Richard M
YR 2017
UL http://biorxiv.org/content/early/2017/11/21/223248.abstract
AB 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 risk score comprising eleven single-nucleotide polymorphisms robustly (P<5x10−8) associated with circulating selenium in genome-wide association studies. In a Mendelian randomization analysis of 72,729 men in the PRACTICAL Consortium (44,825 cases, 27,904 controls), 114 μg/L higher genetically-elevated circulating selenium was not associated with prostate cancer (OR: 1.01; 95% CI: 0.89-1.13). Concordant with findings from SELECT, selenium was weakly associated with advanced (including high-grade) prostate cancer (OR: 1.21; 95% CI: 0.98-1.49) and type 2 diabetes (OR: 1.18; 95% CI: 0.97-1.43; in a type 2 diabetes GWAS meta-analysis with up to 49,266 cases, 249,906 controls). Mendelian randomization mirrored the outcome of selenium supplementation in SELECT and may offer an approach for the prioritization of interventions for follow-up in large-scale randomized controlled trials.