Am J Clin Nutr. 2021 Oct 7:nqab342. doi: 10.1093/ajcn/nqab342. Online ahead of print.
ABSTRACT
BACKGROUND: Recent observational studies have suggested that circulating phosphorus levels are positively associated with risk of prostate cancer. However, little is known about the causal direction of the association.
OBJECTIVE: To explore the potential causal relationship between circulating phosphorus and risk of prostate cancer, we conducted a Mendelian randomization (MR) study.
DESIGN: Summary statistics of prostate cancer were obtained from a meta-analysis of genome-wide association studies (GWAS) consisting of 79,148 cases and 61,106 controls. Single nucleotide polymorphisms (SNP) associated with serum phosphorus level 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, weighted-median, maximum likelihood-based, MR-Egger regression and MR-PRESSO test. We also performed a meta-analysis of observational studies to assess the associations of dietary phosphorus intake and serum phosphorus level with risk of prostate cancer.
RESULTS: In the MR analysis, a total of 125 independent SNPs associated with serum phosphorus levels were used as instrumental variables. Genetically predicted serum phosphorus levels were associated with a 19% increased risk of prostate cancer (95% confidence interval (CI): 9%, 31%) per one 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, eight studies for dietary phosphorus intake and four for serum phosphorus levels were included involving a total of 669,080 participants. Consistently, high dietary phosphorus intake and serum phosphorus levels were associated with an 8% (95% CI: 4%, 12%) and 7% (95% CI: 1%, 14%) increase in prostate cancer risk, respectively.
CONCLUSIONS: Our study suggested a potential causal relationship 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.
PMID:34617559 | DOI:10.1093/ajcn/nqab342