scholarly journals Lower circulating adiponectin is associated with higher risk of renal cell carcinoma: A meta-analysis

2020 ◽  
Vol 35 (1) ◽  
pp. 57-64
Author(s):  
Jiajie Fang ◽  
Xuanli Xu ◽  
Qiqi Mao ◽  
Yufan Ying ◽  
Xu Zhang ◽  
...  

Background: Changes in circulating adiponectin have been related to the risks of various cancers. However, the association between circulating adiponectin and the risk of renal cell carcinoma has not been fully determined. A meta-analysis was performed to evaluate the relationship between circulating adiponectin and renal cell carcinoma risk. Methods: Observational studies that evaluated the association between circulating adiponectin and renal cell carcinoma risk were identified via a systematic search of PubMed and Embase databases. The difference between circulating adiponectin in renal cell carcinoma cases and healthy controls, and the multivariable adjusted association between circulating adiponectin and renal cell carcinoma risk were evaluated. A random effects model was used if significant heterogeneity existed; otherwise a fixed effects model was applied. Results: Eight case-control studies with 2624 renal cell carcinoma cases and 2904 healthy controls were included. Pooled results showed that circulating adiponectin was significantly lower in renal cell carcinoma cases than in healthy controls (mean difference = −1.08 ug/mL; 95% confidence interval (CI) −1.62, −0.54; P < 0.001). Higher circulating adiponectin was independently associated with a significantly lowered risk of renal cell carcinoma (adjusted odds ratio for 1 SD increment of adiponectin = 0.78; 95% CI: 0.63, 0.96; P = 0.02). Subgroup analyses according to characteristics including study design, ethnics of participants, blood samples, numbers of participants, mean ages of participants, and study quality showed consistent results. Conclusions: Lower circulating adiponectin is associated with increased risk of renal cell carcinoma. The potential pathophysiological mechanisms underlying the role of circulating adiponectin in the pathogenesis of renal cell carcinoma deserve further investigation.

2016 ◽  
Vol 40 (6) ◽  
pp. 1465-1472 ◽  
Author(s):  
Lei Yang ◽  
Ziyi Zhao ◽  
Shasha Zhao ◽  
Chen Chen ◽  
Xiaofeng Cong ◽  
...  

Background/Aims: Von Hippel-Lindau gene (VHL) has been reported as a tumor-suppressor gene in some cancers. However, the association between VHL promoter hypermethylation and renal cell carcinoma (RCC) remains to be clarified. We are the first to systematically integrate published papers to assess the role of hypermethylated VHL in RCC. Methods: The potential relevant papers were searched via PubMed, Embase, EBSCO, CNKI, and Wanfang databases. The overall odds ratio (OR) and corresponding 95% confidence interval (95% CI) were calculated to evaluate the relationship between VHL promoter hypermethylation and RCC. Results: Finally, a total of 1,998 RCC patients and 294 controls from 13 eligible articles were included in this meta-analysis. Under the fixed-effects model, the pooled OR from seven studies including 596 RCC and 294 nonmalignant samples showed that VHL promoter hypermethylation was significantly higher in cancer than in controls (OR = 7.93, 95% CI = 2.84- 22.15, P < 0.001). Subgroup analysis based on ethnic population and testing method revealed that hypermethylated VHL had a significantly similar OR value in different races and detection methodologies. No significant association was found between hypermethylated VHL and tumor grade, tumor stage, tumor size, histological types, and lymph node status in cancer (all P > 0.05). In the current study, there was no evidence of publication bias as determined by Egger's test (all P > 0.05). Conclusions: In the investigated patients, VHL promoter hypermethylation, which may play an important role in carcinogenesis of RCC, is significantly associated with an increased risk of RCC. However, VHL promoter hypermethylation is not correlated with specific clinicopathological characteristics. Additional future studies are needed to confirm our results.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20611-e20611
Author(s):  
Bilal Iqbal ◽  
Shenhong Wu

e20611 Background: Fatigue is one of the major side effects associated with targeted therapeutic agents in the treatment of renal cell carcinoma (RCC), and has negatively affected the optimal use of these drugs. Currently the risk of fatigue has not been well defined. We performed a systematic review and meta-analysis of published randomized controlled clinical trials (RCT) to determine the risk of fatigue in RCC patients treated with targeted therapy. Methods: Databases including PUBMED, Web of Science, and abstracts presented at the American Society of Clinical Oncology meetings up to October, 2012 were searched to identify relevant studies. Eligible studies included prospective RCTs in which a targeted therapy was compared to a control of non-targeted therapy (placebo or interferon) with data available. Incidences and relative risk (RR) were calculated using a random- or fixed-effects model depending on the heterogeneity of the included studies. Results: A total of 5,192 RCC patients (targeted therapy: 3023, control: 2092) from 11 RCTs were selected for analysis. The overall incidences of all-grade and high-grade (ie, grade 3 or above) fatigue were 45.4% (95% CI: 33.0-58.5%) and 7.6% (95% CI: 4.1-13.5%) respectively. The incidences varied significantly among different agents (P<0.001). In comparison with overall controls, the targeted therapy did not significantly increase the risk of all-grade (RR=1.07, 95% CI: 1.0-1.35, p=0.055) or high-grade fatigue (RR= 1.01, 95% CI: 0.68-1.50, P=0.95). However, the targeted therapy significantly increased the risk of all-grade fatigue (RR 1.60, 95% CI: 1.40-2.32; P<0.001), but not high-grade fatigue (RR 1.74, 95% CI: 0.91-3.32; P=0.095) when compared to placebo. There was no significant difference between the targeted therapy and interferon in the risk of all-grade (RR 1.02, 95% CI: 0.90-1.14; P=0.90) or high-grade fatigue (RR 0.86, 95% CI: 0.55-1.36; P=0.53). Conclusions: The targeted therapy may significantly increase the risk of fatigue in a magnitude comparable to interferon.


2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 515-515
Author(s):  
Kevin Y Xu ◽  
Raji Shameem ◽  
Shenhong Wu

515 Background: Everolimus has been used widely in cancer patients and is associated with the development of hyperglycemia. Due to confounding factors, everolimus’ specific impact on hyperglycemia has not been well understood. We performed a meta-analysis to determine the risk of hyperglycemia attributable to everolimus in cancer patients of varying tumor types. Methods: PubMed and ASCO conference abstracts up to June 2015 were systematically searched. Eligible studies included randomized controlled trials (RCTs) in which everolimus was compared to placebo in cancer patients with or without additional cancer therapies. Heterogeneity tests were performed to examine between-study differences in hyperglycemia. The incidence and relative risk of all-grade and high-grade hyperglycemia attributable to everolimus were determined using random- or fixed-effects models. Results: A total of 7 phase III and 2 phase II RCTs with various tumors were included in our analysis. Everolimus significantly increased the risk of all-grade (RR = 2.60, 95% CI: 2.03-3.31, P < 0.001) and high-grade (RR = 3.00, 95% CI: 1.72-5.23; P < 0.001) hyperglycemia. The incidences of all-grade and high-grade hyperglycemia attributable to everolimus were 6.8% (95% CI: 3.4-13.2%) and 2.5% (95%: 1.2-4.9%) respectively. The everolimus-specific risk of all-grade hyperglycemia varied significantly with tumor types (P < 0.001), with the highest incidence seen in renal cell carcinoma (27.2%, 95% CI: 22.2-32.8%) and the lowest in breast cancer (3.3%, 95% CI: 1.3-8.2%). No significant variation was found between everolimus alone or everolimus in combination with other agents. Similar results were also found for the risk of high-grade hyperglycemia attributable to everolimus. Conclusions: The specific contribution of everolimus to both all-grade and high-grade hyperglycemia may be modified significantly by tumor types. Close monitoring should be given to patients with renal cell carcinoma.


Renal Failure ◽  
2012 ◽  
Vol 34 (8) ◽  
pp. 1052-1057 ◽  
Author(s):  
Hui-Yuan Cheng ◽  
Hao-Yuan You ◽  
Tian-Biao Zhou

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 395-395
Author(s):  
Eunyoung Cho ◽  
Youjin Je ◽  
Toni K. Choueiri

395 Background: Analgesics have been linked to an increased risk of developing renal cell carcinoma (RCC), but the evidence is mixed. Using a meta-analysis design of all available studies, we investigated the association between analgesic use and RCC risk. Methods: We searched the MEDLINE database to identify eligible case-control or cohort studies published in English from 1966 to July 1, 2011 for 3 categories of analgesics: acetaminophen, aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs). Study-specific effect estimates were pooled to compute an overall relative risk (RR) and its 95% confidence interval (CI), using a random effects model, for each category of the analgesics. Analyses were conducted according to regular/any use and high dose or long-duration of use, separately. Results: We identified 18 studies (12 for acetaminophen, 12 for aspirin, and 5 for other NSAIDs) that were performed in 6 countries. Regular/any use of acetaminophen and other NSAIDs were each associated with an increased risk of RCC: pooled RR, 1.33 (95% CI 1.18-1.49) for acetaminophen and 1.26 (95% CI, 1.09-1.44) for other NSAIDs, respectively. For use of aspirin, we found no significant increased risk (pooled RR, 1.14 [95% CI, 0.98-1.33]). Similar risk trends were seen with high dose of analgesics intake. No significant difference in associations was found by study design (case-control vs. cohort), type of controls in case-control study (population based vs. hospital based), outcome (RCC vs. kidney cancer), and gender (male vs. female). There was no indication of publication bias for the 3 analgesics. Conclusions: In this meta-analysis of analgesics use and RCC risk, we found that use of acetaminophen and non-aspirin NSAIDs was associated with a significant increased risk of developing RCC.


2021 ◽  
Vol 12 ◽  
Author(s):  
Fengjun Sun ◽  
Zhuo Chen ◽  
Pu Yao ◽  
Bangbi Weng ◽  
Zhirui Liu ◽  
...  

Background: ABCG2 and ABCB1 are genes related to the pharmacokinetics of sunitinib and have been associated with its toxicity and efficacy. However, the results have been controversial. This study aimed to evaluate the associations of ABCG2 and ABCB1 polymorphisms with sunitinib-induced toxicity and efficacy in renal cell carcinoma (RCC) by meta-analysis.Methods:PubMed, EMBASE, Cochrane Library, and Web of Science were systematically searched for studies investigating the associations of the ABCG2 rs2231142 polymorphism with sunitinib-induced toxicity and the associations of the ABCB1 rs1128503 and ABCB1 rs2032582 polymorphisms with sunitinib-induced toxicity and clinical outcomes. The associations were evaluated by effect size (ES) with 95% confidence intervals (CIs).Results: Eight and five studies were included in the toxicity and efficacy analysis, respectively, including a total of 1081 RCC patients. The ABCG2 rs2231142 A allele was associated with an increased risk of sunitinib-induced thrombocytopenia and hand-foot syndrome (HFS) in Asians (ES = 1.65, 95% CI = 1.15–2.36, p = 0.006; ES = 1.52, 95% CI = 1.02–2.27, p = 0.041). However, the ABCG2 rs2231142 polymorphism was not associated with sunitinib-induced hypertension or neutropenia (ES = 1.09, 95% CI = 0.69–1.73, p = 0.701; ES = 0.87, 95% CI = 0.57–1.31, p = 0.501). Compared with the C allele, the ABCB1 rs1128503 T allele was associated with a decreased risk of sunitinib-induced hypertension but worse progression-free survival (PFS) (ES = 0.44, 95% CI = 0.26–0.77, p = 0.004; ES = 1.36, 95% CI = 1.07–1.73, p = 0.011). There was no significant association between the T allele or C allele of ABCB1 rs1128503 and overall survival (OS) (ES = 0.82, 95% CI = 0.61–1.10, p = 0.184). The ABCB1 rs2032582 T allele was associated with worse PFS than the other alleles (ES = 1.46, 95% CI = 1.14–1.87, p = 0.003), while there was no significant association between the T allele or other alleles and sunitinib-induced hypertension, HFS, or OS (ES = 0.77, 95% CI = 0.46–1.29, p = 0.326; ES = 1.02, 95% CI = 0.65–1.62, p = 0.919; ES = 1.32, 95% CI = 0.85–2.05, p = 0.215).Conclusion: The results indicate that the ABCG2 rs2231142 polymorphism may serve as a predictor of sunitinib-induced thrombocytopenia and HFS in Asians, while the ABCB1 rs1128503 polymorphism may serve as a predictor of sunitinib-induced hypertension, and both the ABCB1 rs1128503 and rs2032582 polymorphisms may serve as predictors of PFS in RCC. These results suggest a possible application of individualized use of sunitinib according to the genetic background of patients.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16536-e16536
Author(s):  
Bareia Chaudhry ◽  
Shenhong Wu

e16536 Background: Axitinib has been used extensively as a single agent or in combination with immunotherapy in the treatment of advanced renal cell carcinoma. It can be often discontinued due to adverse events. A meta-analysis of clinical trials was performed to evaluate the overall tolerability of axitinib in this setting. Methods: PubMed (Up to November 2020) was searched to identify clinical trials of axitinib in advanced or metastatic renal cell carcinoma. Reported data was collected to include axitinib and control discontinuation due to adverse events. A random or fixed effects model was used to determine summary incidences, relative risks, and 95% confidence intervals depending on the heterogeneity of included studies. Results: A total of 11 studies including 4,056 patients (axitinib alone n = 1384, axitinib combination n = 987, control n = 1685) were included for analysis. The summary discontinuation rate for axitinib due to adverse events was 13.4% (95% CI; 11.7-15.2%) with 8.9% (95% CI: 5.3-14.6%) as a single agent and 26.6% (95% CI:17.8 –37.8%) in combination with other agents. In comparison with controls based on randomized controlled studies, axitinib overall has similar discontinuation rate due to adverse events (RR: 1.18, 95% CI: 0.77-1.80). However, there was a significantly higher discontinuation rate with axitinib in combination with other agents including immunotherapeutic agents PD-L1 inhibitors than control treatment (RR: 1.52, 95% CI: 1.24-1.86). Conclusions: The tolerability of axitinib may vary significantly with its use as a single agent or in combination in the treatment of advanced renal cell carcinoma. Further studies are needed to improve its tolerability as a part of combination therapy.


2021 ◽  
Author(s):  
YuPeng Liu ◽  
Lin Ma ◽  
YuXue Zhang ◽  
ZhiGang Wu ◽  
Xiaodong Liu

Abstract Purpose: Renal cell carcinoma (RCC) is becoming more common as a urinary system malignancy. There is a growing body of evidence supporting an important role of DNA methylation alteration involved in the initiation of RCC, but the current findings are inconsistent and controversial. Thus, we performed this systematic review and meta-analysis to comprehensively assess the associations between methylation status of tumour suppressor genes and the incidence risk of RCC. Methods: This study has been registered on PROSPERO (CRD42019130782) and was reported according to the PRISMA guidelines. We systematically searched the PubMed, EMBASE and CNKI databases for relevant studies. The effect estimates were summarized using random-effect models. Results: A total of 21 case-control studies containing 1,912 participants were included. Overall, abnormal hypermethylation of RASSF1A was associated with a significantly increased risk of RCC (OR, 6.612, 95% CI: 1.926-22.697, P = 0.003), especially in the American populations (OR, 18.429, 95% CI: 3.072-110.536, P = 0.001). An increased RCC risk was also associated with hypermethylation of SFRP1 and GSTP1 (OR, 3.995, 95% CI: 1.607-9.934, P = 0.003; OR, 4.508, 95% CI: 1.004-20.239, P = 0.049; respectively); however, the results for SFRP1 and GSTP1 were non-conclusive due to the limited number of studies included and the inconsistency across sensitivity analyses. There was no obvious association for the other genes. Conclusion: This study demonstrated a statistically and robustly positive association of aberrant hypermethylation of RASSF1A with an increased risk of developing RCC, indicating a potentially useful biomarker to predict the RCC incidence risk.


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