Genetically predicted serum urate and cancer risk: a Mendelian randomization study

To evaluate the causal effect of genetically predicted serum urate (SU) levels on the risk of overall and major site-specific cancers in individuals of European ancestry, using Mendelian randomization (MR) analysis. Data from two population-based cohorts from southern Sweden, the Malmö Diet and Cancer Study (MDCS) and Malmö Preventive Project (MPP), and summary-statistics data from the Global Urate Genetic Consortium (GUGC) and UK Biobank cohort were used. A set of 26 SU-related variants was used as instrumental variables to perform a range of one- (using MDCS-MPP) and two-sample (using GUGC and UK Biobank) MR analyses. Causal relationships were assessed between genetically determined SU and 13 site-specific cancers (bladder, breast, color ectal, gastric, hepatic, lung, pancreatic, prostate, renal, skin, lymphatic, haematopoietic, and gynaecological cancers, and brain tumour) and 'any cancer'. We also performed epidemiological association analyses on individual-level data to determine SU-cancer relationships. There was some suggestive evidence of an association between higher levels of genetically predicted SU and lower risk of brain (p = 0.04; one-sample MR) and colorectal (p = 0.02; two-sample MR) cancers, although these findings were not consistent across both MR approaches. No significant associations were observed between SU levels and the risk of other cancers (all p > 0.05). Our MR study found no consistent evidence of a causal effect of genetically predicted SU on overall or Q3 common site-specific cancers in European individuals.