Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Clin Chem. 2017 Jun;63(6):1151-1160. doi: 10.1373/clinchem.2016.268185. Epub 2017 Apr 20.
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.
We performed observational and genetic analyses using plasma urate and the urate solute carrier family 2 member 9 () 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.
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 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.
High plasma urate was both observationally and genetically associated with high cancer incidence and high all-cause mortality, suggesting causal relationships.
观察性研究表明，血浆尿酸水平升高与癌症风险增加相关。本研究采用孟德尔随机化设计，旨在检验高浓度血浆尿酸与癌症发病率和全因死亡率升高相关的假设，该假设既基于观察性研究，也基于遗传学研究。
我们对 86210 名来自哥本哈根普通人群研究的个体的血浆尿酸和溶质载体家族 2 成员 9 （SLC2A9）基因 rs7442295 基因型进行了观察性和遗传学分析。癌症和死亡率终点来自国家癌症和死亡登记处。使用 Cox 回归、Fine 和 Gray 竞争风险回归以及工具变量分析计算了癌症和全因死亡率的发生率和风险。
在癌症中位随访时间为 3.9 年，全因死亡率中位随访时间为 4.9 年期间，3243 人被诊断为癌症，3978 人死亡。观察性研究表明，血浆尿酸水平升高 50%，与多变量调整后的癌症发病率风险比为 1.11（95%CI，1.05-1.18）和全因死亡率风险比为 1.07（1.01-1.13）相关。rs7442295 的每个 A 等位基因与血浆尿酸升高 9%相关，癌症发病率风险比为 1.07（1.01-1.14），全因死亡率风险比为 1.07（1.02-1.13）。在工具变量分析中，遗传决定的血浆尿酸水平升高 50%，与癌症发病率的比值比为 1.22（1.02-1.47），与全因死亡率的比值比为 1.49（1.13-1.93）。
高血浆尿酸与癌症发病率和全因死亡率升高均具有观察性和遗传学相关性，提示存在因果关系。
