Recent studies suggest that fructose, as well as its metabolite, uric acid, have been associated with increased risk for both cancer incidence and growth. Both substances are known to cause oxidative stress to mitochondria and to reduce adenosine triphosphate (ATP) production by blocking aconitase in the Krebs cycle. The uricase mutation that occurred in the Miocene has been reported to increase serum uric acid and to amplify the effects of fructose to stimulate fat accumulation. Here we tested whether the uricase mutation can also stimulate tumor growth. Experiments were performed in mice in which uricase was inactivated by either knocking out the gene or by inhibiting uricase with oxonic acid. We also studied mice transgenic for uricase. These mice were injected with breast cancer cells and followed for 4 weeks. The inhibition or knockout of uricase was associated with a remarkable increase in tumor growth and metastases. In contrast, transgenic uricase mice showed reduced tumor growth. A loss of uricase increases the risk for tumor growth. Prior studies have shown that the loss of the mutation facilitated the ability of fructose to increase fat which provided a survival advantage for our ancestors that came close to extinction from starvation in the mid Miocene. Today, however, excessive fructose intake is rampant and increasing our risk not only for obesity and metabolic syndrome, but also cancer. Obesity-associated cancer may be due, in part, to a mutation 15 million years ago that acted as a thrifty gene.

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简报：人体尿酸酶突变增加我们患癌症的风险

最近的研究表明，果糖及其代谢物尿酸与癌症发病率和增长的风险增加有关。已知这两种物质都会对线粒体造成氧化应激，并通过阻断三羧酸循环中的乌头酸酶来减少三磷酸腺苷 (ATP) 的产生。据报道，发生在中新世的尿酸酶突变会增加血清尿酸并放大果糖刺激脂肪积累的作用。在这里，我们测试了尿酸酶突变是否也可以刺激肿瘤生长。在小鼠中进行了实验，其中通过敲除基因或通过用氧酸抑制尿酸酶使尿酸酶失活。我们还研究了尿酸酶转基因小鼠。这些小鼠被注射了乳腺癌细胞并跟踪了 4 周。尿酸酶的抑制或敲除与肿瘤生长和转移的显着增加有关。相比之下，转基因尿酸酶小鼠的肿瘤生长减少。尿酸酶的丧失会增加肿瘤生长的风险。先前的研究表明，突变的缺失促进了果糖增加脂肪的能力，这为我们在中新世中期濒临饥饿而濒临灭绝的祖先提供了生存优势。然而，今天，过量的果糖摄入很猖獗，不仅会增加我们患肥胖症和代谢综合征的风险，还会增加患癌症的风险。与肥胖相关的癌症可能部分归因于 1500 万年前充当节俭基因的突变。尿酸酶的丧失会增加肿瘤生长的风险。先前的研究表明，突变的缺失促进了果糖增加脂肪的能力，这为我们在中新世中期濒临饥饿而濒临灭绝的祖先提供了生存优势。然而，今天，过量的果糖摄入很猖獗，不仅会增加我们患肥胖症和代谢综合征的风险，还会增加患癌症的风险。与肥胖相关的癌症可能部分归因于 1500 万年前充当节俭基因的突变。尿酸酶的丧失会增加肿瘤生长的风险。先前的研究表明，突变的缺失促进了果糖增加脂肪的能力，这为我们在中新世中期濒临饥饿而濒临灭绝的祖先提供了生存优势。然而，今天，过量的果糖摄入很猖獗，不仅会增加我们患肥胖症和代谢综合征的风险，还会增加患癌症的风险。与肥胖相关的癌症可能部分归因于 1500 万年前充当节俭基因的突变。过量的果糖摄入非常普遍，不仅会增加我们患肥胖症和代谢综合征的风险，还会增加患癌症的风险。与肥胖相关的癌症可能部分归因于 1500 万年前充当节俭基因的突变。过量的果糖摄入非常普遍，不仅会增加我们患肥胖症和代谢综合征的风险，还会增加患癌症的风险。与肥胖相关的癌症可能部分归因于 1500 万年前充当节俭基因的突变。