What is the relationship between elevated uric acid levels and cancer?

The Relationship Between Elevated Uric Acid Levels and Cancer

Elevated uric acid levels are associated with increased cancer risk, recurrence, and mortality, with hyperuricemia serving as both a potential marker and contributor to cancer pathogenesis. 1

Pathophysiological Connection Between Uric Acid and Cancer

• Uric acid is a product of purine metabolism, produced through the catabolism of purine nucleic acids to hypoxanthine, then xanthine, and finally to uric acid by the enzyme xanthine oxidase 2
• While uric acid can function as a systemic antioxidant, its pro-inflammatory properties have been implicated in cancer pathogenesis 1
• Hyperuricemia is commonly observed in malignancies with high proliferative rates and large tumor burden due to rapid cell turnover and release of nucleic acids 2
• The release and subsequent catabolism of nucleic acids from cancer cells results in hyperuricemia, particularly in hematologic malignancies 2

Epidemiological Evidence

• A large Swedish cohort study of 493,281 individuals found a positive association between uric acid levels and overall cancer risk 3
  • Hazard ratio for overall cancer for the highest quartile of uric acid compared to the lowest was 1.08 (95% CI: 1.05-1.11) in men and 1.12 (1.09-1.16) in women 3
• A systematic review and meta-analysis showed a modest increase in overall cancer risk with elevated uric acid levels, with a relative risk of 1.11 (95% CI: 0.94-1.27) 4
• In a study of 316 cancer patients, blood uric acid levels were found to be higher in all cancer patients compared to normal subjects 5
  • Particularly high positive rates were observed in kidney cancer (93.30%) and bladder cancer (90.90%) 5

Cancer-Specific Associations

• Site-specific analyses have shown positive associations between uric acid and:
  • Colorectal, hepatobiliary, kidney, and non-melanoma skin cancers in men 3
  • Head and neck cancers in women 3
• Inverse associations have been observed for:
  • Pulmonary and central nervous system cancers in men 3
  • Breast, lymphatic, hematological, and central nervous system malignancies in women 3
• In breast cancer specifically, high uric acid concentration has been identified as an independent prognostic factor predicting poor overall survival (HR 2.13,95% CI 1.15-3.94) 6

Uric Acid in Tumor Lysis Syndrome (TLS)

• Tumor Lysis Syndrome (TLS) represents an extreme manifestation of the relationship between cancer and uric acid 2
• TLS occurs most frequently in patients with hematologic malignancies, particularly Burkitt's lymphoma, acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML) 2
• High uric acid levels (≥ 8 mg/dL) significantly increase the risk of developing TLS compared to medium (≥ 4 but < 8 mg/dL) or low (< 4 mg/dL) levels 2
• The precipitation of uric acid in renal tubules can lead to renal insufficiency or failure, a common complication of TLS 2

Mechanisms Linking Uric Acid and Cancer

• Chronic inflammation associated with hyperuricemia may contribute to cancer development and progression 1
• Hyperuricemia is associated with obesity, Type 2 Diabetes Mellitus, and metabolic syndrome, which are also risk factors for cancer 1
• Some cancer cells express low intracellular levels of Xanthine Oxidoreductase (XOR), which is associated with increased cancer aggressiveness and poor clinical outcomes 1

Clinical Implications

• Monitoring uric acid levels may have prognostic value in cancer patients, particularly those with breast cancer 6
• Pharmacological modulation of hyperuricemia could potentially augment anti-cancer therapeutic strategies 1
• In patients at risk for TLS, prophylactic measures to control uric acid levels are essential to prevent complications 2
• Treatment options include allopurinol (which blocks uric acid formation) and recombinant urate oxidase (which promotes uric acid catabolism) 2

Pitfalls and Considerations

• Uric acid levels may fluctuate during acute inflammatory states, potentially affecting interpretation in cancer patients 7
• Systemic pharmacological inhibition of XOR may worsen clinical outcomes in some cancers, suggesting the need for targeted approaches 1
• When interpreting uric acid levels, laboratory-specific reference ranges should be considered, as they may vary 7
• The relationship between uric acid and cancer appears bidirectional—cancer can cause hyperuricemia, and hyperuricemia may contribute to cancer risk 1, 3