Camilla J Kobylecki1,2, Shoaib Afzal1,2, Børge G Nordestgaard3,2. 1. Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark. 2. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. 3. Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark; Boerge.Nordestgaard@regionh.dk.
Abstract
BACKGROUND: Observationally, high plasma urate is associated with high risk of cancer. We used a Mendelian randomization design to test the hypothesis that high concentrations of plasma urate are associated with high cancer incidence and all-cause mortality observationally and genetically. METHODS: We performed observational and genetic analyses using plasma urate and the urate solute carrier family 2 member 9 (SLC2A9) rs7442295 genotype in 86210 individuals from the Copenhagen General Population Study. Cancer and mortality end points were from national cancer and death registries. Incidences and risk of cancer and all-cause mortality were calculated using Cox regression, Fine and Gray competing-risks regression, and instrumental variable analyses. RESULTS: During a median follow-up time of 3.9 years for cancer and 4.9 years for all-cause mortality, 3243 individuals received a diagnosis of cancer and 3978 died. Observationally, 50% higher plasma urate was associated with multivariable-adjusted hazard ratios of 1.11 (95% CI, 1.05-1.18) for cancer incidence and 1.07 (1.01-1.13) for all-cause mortality. Each A-allele of the SLC2A9 rs7442295 was associated with 9% higher plasma urate and hazard ratios of 1.07 (1.01-1.14) for cancer incidence and 1.07 (1.02-1.13) for all-cause mortality. In instrumental variable analyses, the odds ratios for a genetically determined 50% higher plasma urate was 1.22 (1.02-1.47) for cancer incidence and 1.49 (1.13-1.93) for all-cause mortality. CONCLUSIONS:High plasma urate was both observationally and genetically associated with high cancer incidence and high all-cause mortality, suggesting causal relationships.
RCT Entities:
BACKGROUND: Observationally, high plasma urate is associated with high risk of cancer. We used a Mendelian randomization design to test the hypothesis that high concentrations of plasma urate are associated with high cancer incidence and all-cause mortality observationally and genetically. METHODS: We performed observational and genetic analyses using plasma urate and the uratesolute carrier family 2 member 9 (SLC2A9) rs7442295 genotype in 86210 individuals from the Copenhagen General Population Study. Cancer and mortality end points were from national cancer and death registries. Incidences and risk of cancer and all-cause mortality were calculated using Cox regression, Fine and Gray competing-risks regression, and instrumental variable analyses. RESULTS: During a median follow-up time of 3.9 years for cancer and 4.9 years for all-cause mortality, 3243 individuals received a diagnosis of cancer and 3978 died. Observationally, 50% higher plasma urate was associated with multivariable-adjusted hazard ratios of 1.11 (95% CI, 1.05-1.18) for cancer incidence and 1.07 (1.01-1.13) for all-cause mortality. Each A-allele of the SLC2A9rs7442295 was associated with 9% higher plasma urate and hazard ratios of 1.07 (1.01-1.14) for cancer incidence and 1.07 (1.02-1.13) for all-cause mortality. In instrumental variable analyses, the odds ratios for a genetically determined 50% higher plasma urate was 1.22 (1.02-1.47) for cancer incidence and 1.49 (1.13-1.93) for all-cause mortality. CONCLUSIONS: High plasma urate was both observationally and genetically associated with high cancer incidence and high all-cause mortality, suggesting causal relationships.
Authors: Richard J Johnson; Laura G Sánchez-Lozada; Takahiko Nakagawa; Bernardo Rodriguez-Iturbe; Dean Tolan; Eric A Gaucher; Peter Andrews; Miguel A Lanaspa Journal: Obesity (Silver Spring) Date: 2022-10 Impact factor: 9.298