Contribution of uric acid to cancer risk, recurrence, and mortality

Abstract

Two risk factors for the development and progression of cancers that are amenable to life style modification are chronic inflammation and the metabolic syndrome. This review proposes two new targets that may mechanistically integrate inflammation and metabolic syndrome, have been largely ignored, and are known to be druggable. Recent evidence has demonstrated that elevated serum uric acid (hyperuricemia) is associated with excess cancer risk, recurrence, and mortality. Although uric acid (UA) can function as a systemic antioxidant, its pro‐inflammatory properties have been postulated to play an important role in the pathogenesis of cancer. Furthermore, obesity, Type 2 Diabetes Mellitus (T2DM), and the metabolic syndrome (MetS) are also associated with excess cancer, chronic inflammation, and with hyperuricemia, suggesting that UA may represent an important link between these disorders and the development of cancer. While pharmacological modulation of hyperuricemia could in principal augment anti‐cancer therapeutic strategies, some cancer cells express low intracellular levels of the enzyme Xanthine Oxidoreductase (XOR) that are associated with increased cancer aggressiveness and poor clinical outcome. Thus, systemic pharmacological inhibition of XOR may worsen clinical outcome, and specific strategies that target serum uric acid (SUA) without inhibiting tumor cell XOR may create new therapeutic opportunities for cancer associated with hyperuricemia. This review will summarize the evidence that elevated SUA may be a true risk factor for cancer incidence and mortality, and mechanisms by which UA may contribute to cancer pathogenesis will be discussed in the hope that these will identify new opportunities for cancer management.

Upregulation of gamma-glutamyl-transpeptidase activity and uric acid level in mixed chemical exposure: implications for mutagenic and preneoplastic events

“…This appears to make uric acid a potential biomarker of these events and their consequences. This observation therefore appears to support the hypothesis that uric acid is a potent antioxidant that might protect against cancer (Ames et al, 1981) and subsequent supported by more recent studies of the relationship between uric acid and cancer risk (Ghaemi-Oskouie and Shi, 2011;Fini, 2012;Kang and Ha, 2014;Yan et al, 2015). Therefore, the significant positive correlation between duration of exposure and uric acid concentration in the exposed group may be an indirect reflection of and/or a corroboration of the strength of association between chemical exposure and risk of cancer.…”

“…Therefore, the significant positive correlation between duration of exposure and uric acid concentration in the exposed group may be an indirect reflection of and/or a corroboration of the strength of association between chemical exposure and risk of cancer. However, some recent reports (Fini, 2012;Kang and Ha, 2014;Yan et al, 2015) are not in agreement with the hypothesis that uric acid might offer protection against occurrence and indirectly as a marker of pre-neoplastic events. The reason for this divergence is unclear, indicating need for more studies.…”

Targeting roles of inflammatory microenvironment in lung cancer and metastasis

“…Tumor promoters like phorbol esters per se are potent inducers of inflammation [61]. Inflammation-induced tumor promotion may occur during tumor development and activate premalignant lesions through production and activation of CICs, inflammatory mediators, and transcription factors, such as NF-κB, STAT3 and AP-1, in premalignant cells [76,77] (Fig. 4).…”

Beneficial Effect of a Low Dose of Ethanol on Liver Function and Serum Urate in Rats Fed a High-Fat Diet

“…Modest alterations in the production, solubility, or excretion of urate can cause hyperuricemia. Previous studies show hyperuricemia is a risk factor for gout, cancer, and components of metabolic syndrome, such as hypertension and insulin resistance (19)(20)(21). Epidemiological studies suggest moderate alcohol intake reduces the risks of diseases such as cancers, diabetes, and cardiovascular diseases (1,2).…”