Genetically predicted serum urate and the risk of all-cause and site-specific cancer: A Mendelian randomization study

Background Positive associations between urate levels and gout and the risk of some cancer types (urogenital, prostate, gastrointestinal and lung) have been reported in several observational studies; however, whether the relationship is causal remains uncertain. Objectives The study aim was to evaluate associations between genetically predicted levels of serum urate (SU) and cancer risk (overall and major cancer types) in individuals of European ancestry using Mendelian randomization (MR) analysis. Methods A set of 26 SU-related variants was used as proxy instrument to perform a range of one and two-sample MR analyses in individual-level and publicly available GWAS (genome-wide association study data), respectively. The causal relationship was assessed between genetically determined SU and 13 site-specific (bladder, breast, colorectal, gastric, hepatic, lung, pancreatic, prostate, renal, skin, lymphatic and hematopoietic cancers, gynecological cancers, and brain tumor) and all-cause cancer. We also performed epidemiological association analyses in individual-level data to determine a SU-cancer relationship. Results There was some suggestive evidence for an association between higher levels of genetically predicted SU and lower risk of brain (p = 0.04 in 1-sample MR) and colorectal (p = 0.02 in 2-sample MR) cancers, although not consistent in the two analyses. There were no indications for associations between genetically predicted SU and any of the other cancers (all p  > 0.05). Conclusions Our MR study, using a series of causal inference approaches, provides suggestive but inconsistent evidence of an effect of genetically predicted SU on brain and colorectal cancers in individuals of European ancestry.