Circulating phosphorus concentration and risk of prostate cancer: a Mendelian randomization study

Abstract

Recent observational studies have suggested that circulating phosphorus concentrations are positively associated with the risk of prostate cancer. However, little is known about the causal direction of the association. To explore the potential causal relation between circulating phosphorus and risk of prostate cancer, we conducted a Mendelian randomization (MR) study. Summary statistics of prostate cancer were obtained from a meta-analysis of genome-wide association studies (GWASs) consisting of 79,148 cases and 61,106 controls. Single-nucleotide polymorphisms (SNPs) associated with serum phosphorus concentration were selected from a GWAS of 291,408 individuals from the UK Biobank. MR analysis was performed using the inverse variance weighted (IVW) method, supplemented with simple median method, weighted median method, maximum likelihood-based method, MR-Egger regression, and the MR pleiotropy residual sum and outlier test. We also performed a meta-analysis of observational studies to assess the associations of dietary phosphorus intake and serum phosphorus concentration with risk of prostate cancer. In the MR analysis, a total of 125 independent SNPs associated with serum phosphorus concentrations were used as instrumental variables. Genetically predicted serum phosphorus concentrations were associated with a 19% increased risk of prostate cancer (95% CI: 9%, 31%) per 1-SD increment of serum phosphorus by IVW (P=1.82×10-4). Sensitivity analyses using alternative MR methods produced similar positive associations, and no evidence of pleiotropy was detected by MR-Egger regression (P=0.422). For meta-analysis, 8 studies for dietary phosphorus intake and 4 for serum phosphorus concentrations were included involving a total of 669,080 participants. Consistently, high dietary phosphorus intake and serum phosphorus concentrations were associated with an 8% (95% CI: 4%, 12%) and 7% (95% CI: 1%, 14%) increase in prostate cancer risk, respectively. Our study suggested a potential causal relation between circulating phosphorus and risk of prostate cancer. Further studies are warranted to elucidate the underlying mechanism of phosphorus in the development of prostate cancer.