Serum uric acid levels and risk of kidney cancer incidence and mortality: A prospective cohort study

Dai, Xiaoyu; He, Qiangsheng; Jing, Zhong; Yuan, Jinqiu

doi:10.1002/cam4.3214

Cited by 16 publications

(12 citation statements)

References 18 publications

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“…Among the other kidney function biomarkers, we further discovered an underlying negative genetic causal inference of urate on kidney cancer in the sensitivity analysis, excluding instrumental SNPs related to body composition and diabetes. That was interestingly opposite to many previous observational studies 60,61 . The reason might due to the horizontal pleiotropy, which could influence the direction of causality, as the intercepts of MR–Egger were significant( p = 0.001).…”

Section: Discussioncontrasting

confidence: 86%

“…That was interestingly opposite to many previous observational studies. 60 , 61 The reason might due to the horizontal pleiotropy, which could influence the direction of causality, as the intercepts of MR–Egger were significant( p = 0.001). In addition, this might support the potentially protective role of urate in cancers as an antioxidant defense.…”

Section: Discussionmentioning

confidence: 99%

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Impairment of kidney function and kidney cancer: A bidirectional Mendelian randomization study

Lin

Yang

et al. 2022

Cancer Medicine

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Background Many observational epidemiology studies discovered that kidney cancer and impaired kidney function have a bidirectional relationship. However, it remains unclear whether these two kinds of traits are causally linked. In this study, we aimed to investigate the bidirectional causal relation between kidney cancer and kidney function biomarkers (creatinine‐based estimated glomerular filtration rate (eGFRcrea), cystatin C‐based estimated glomerular filtration rate (eGFRcys), blood urea nitrogen (BUN), serum urate, and urinary albumin‐to‐creatinine ratio (UACR)). Methods For both directions, single‐nucleotide polymorphisms (SNPs), as genetic instruments, for the five kidney function traits were selected from up to 1,004,040 individuals, and SNPs for kidney cancer were from 408,786 participants(1338 cases). In the main analysis, we applied two state‐of‐the‐art MR methods, namely, contamination mixture and Robust Adjusted Profile Score to downweight the effect of weak instrument bias, pleiotropy, and extreme outliers. We additionally conducted traditional MR analyses as sensitivity analyses. Summary‐level data of European ancestry were extracted from UK Biobank, Chronic Kidney Disease Genetics Consortium, and Kaiser Permanente. Results Based on 99 SNPs, we found that the eGFRcrea had a significant negative causal effect on the risk of kidney cancer (OR = 0.007, 95% CI:2.6 × 10 −4 –0.569, p = 0.041). After adjusting for body composition or diabetes, urate had a significant negative causal effect on kidney cancer (OR <1, p < 0.05). For UACR, it showed a strong causal effect on kidney cancer, after adjusting for body composition (OR = 14.503, 95% CI: 2.546–96.001, p = 0.032). Due to lacking significant signals and effect power for the reverse MR, further investigations are warranted. Conclusions Our study suggested a potential causal effect of damaged kidney function on kidney cancer. EGFRcrea and UACR might be causally associated with kidney cancer, especially when patients were comorbid with obesity or diabetes. We called for larger sample‐size studies to further unravel the underlying causal relationship and the exact mechanism.

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Section: Discussioncontrasting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Impairment of kidney function and kidney cancer: A bidirectional Mendelian randomization study

Lin

Yang

et al. 2022

Cancer Medicine

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“…Hypoxanthine, xanthine, and uric acid are the last components in the catabolism of purine nucleotides adenosine and guanosine phosphate. Extensive epidemiological evidence showed that elevated baseline serum uric acid (hyperuricemia) is associated with increased cancer risk across cancer types [ 26 ], and in RCC in particular [ 27 ]. The effect seems to be exerted by the upregulation of key components of chronic inflammatory pathways such as adiponectin, C-reactive protein, and leptin [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

SERS Liquid Biopsy Profiling of Serum for the Diagnosis of Kidney Cancer

et al. 2022

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Renal cancer (RC) represents 3% of all cancers, with a 2% annual increase in incidence worldwide, opening the discussion about the need for screening. However, no established screening tool currently exists for RC. To tackle this issue, we assessed surface-enhanced Raman scattering (SERS) profiling of serum as a liquid biopsy strategy to detect renal cell carcinoma (RCC), the most prevalent histologic subtype of RC. Thus, serum samples were collected from 23 patients with RCC and 27 controls (CTRL) presenting with a benign urological pathology such as lithiasis or benign prostatic hypertrophy. SERS profiling of deproteinized serum yielded SERS band spectra attributed mainly to purine metabolites, which exhibited higher intensities in the RCC group, and Raman bands of carotenoids, which exhibited lower intensities in the RCC group. Principal component analysis (PCA) of the SERS spectra showed a tendency for the unsupervised clustering of the two groups. Next, three machine learning algorithms (random forest, kNN, naïve Bayes) were implemented as supervised classification algorithms for achieving discrimination between the RCC and CTRL groups, yielding an AUC of 0.78 for random forest, 0.78 for kNN, and 0.76 for naïve Bayes (average AUC 0.77 ± 0.01). The present study highlights the potential of SERS liquid biopsy as a diagnostic and screening strategy for RCC. Further studies involving large cohorts and other urologic malignancies as controls are needed to validate the proposed SERS approach.

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“…Uric acid is the end product of the purine metabolism pathway, and is an antioxidant scavenging free radicals in the body (8,9). Recent evidences have linked serum uric acid (SUA) to cancer risks in adulthood (10,11). Studies show that hyperuricemia is associated with an increased cancer incidence and mortality (12), while some other conflicting reports have suggested a protective role of SUA in cancer due to its antioxidant properties (13,14).…”

Section: Introductionmentioning

confidence: 99%

Elevated serum uric acid is associated with the risk of advanced staging and vascular involvement in patients with hepatoblastoma: a 14-year retrospective study

Zhou

et al. 2023

Front. Oncol.

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BackgroundUric acid is the end product of the purine metabolism pathway, and has been linked to cancer risks and prognosis, but its relationship with hepatoblastoma (HB) remains unclear. This study aims to investigate the association between serum uric acid (SUA) and the advanced tumor staging and unfavorable extra-parenchymal tumor characteristics in patients with HB.MethodsThis study enrolled pediatric patients from Xinhua Hospital between 2007 to 2021. A total of 101 participants with newly diagnosed HB were recruited in the study. PRETreatment EXTent of disease (PRETEXT)/PostTreatment Extent of disease (POSTTEXT) staging were evaluated at diagnosis and following neoadjuvant chemotherapy (NAC). Adjusted smoothing spline plots, subgroup analysis and multivariate logistic regression analysis were conducted to estimate the association of different levels of SUA with the advanced tumor staging and present annotation factors.ResultsIn accordance with SUA tertiles, those patients with higher pretreatment SUA levels showed increased percentages of PRETEXT group IV, vessel involvement and multifocality of tumors. After fully adjustment with the confounding factors, SUA was positively associated with advanced PRETEXT stage IV (OR: 1.72, 95%CI 1.15-2.57, p=0.0080), as well as vascular invasion (OR: 1.29, 95%CI 1.01-1.64, p=0.0396). Compared with the lowest SUA concentration tertile, the highest tertile were independently associated with vessel involvement of tumor in all of the adjusted models. Following NAC, SUA levels were significantly reduced in response to the downstaging of tumors. SUA remained positively associated with advanced POSTTEXT staging and vessel involvement in adjusted models. Patients with highest tertile of posttreatment SUA showed worse 5-year EFS and OS.ConclusionElevated SUA were associated with an increased occurrence of advanced PRETEXT/POSTTEXT staging and unfavorable vessel involvement at diagnosis and following NAC in patients with HB. High posttreatment SUA reflected poor tumor responses to NAC. This study linked SUA, a non-invasive laboratory test, with tumor staging and risk prediction for HB.

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Serum uric acid levels and risk of kidney cancer incidence and mortality: A prospective cohort study

Cited by 16 publications

References 18 publications

Impairment of kidney function and kidney cancer: A bidirectional Mendelian randomization study

Impairment of kidney function and kidney cancer: A bidirectional Mendelian randomization study

SERS Liquid Biopsy Profiling of Serum for the Diagnosis of Kidney Cancer

Elevated serum uric acid is associated with the risk of advanced staging and vascular involvement in patients with hepatoblastoma: a 14-year retrospective study

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