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- Johansson, Mattias, et al.
(author)
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The influence of obesity-related factors in the etiology of renal cell carcinoma—A mendelian randomization study
- 2019
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In: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 16:1
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Journal article (peer-reviewed)abstract
- Background: Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation.Methods and findings: Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44–1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40–1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44–1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30–2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11–1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84–1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose.Conclusions: This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.
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| 2. |
- Kriegmair, Maximilian C., et al.
(author)
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Systematic Review of the Management of Local Kidney Cancer Relapse
- 2018
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In: European Urology Oncology. - : Elsevier. - 2588-9311. ; 1:6, s. 512-523
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Research review (peer-reviewed)abstract
- Context: Management of locally recurrent renal cancer is complex.Objective: In this systematic review we analyse the available literature on the management of local renal cancer recurrence.Evidence acquisition: A systematic search (PubMed, Web of Science, CINAHL, Clinical Trials, and Scopus) of English literature from 2000 to 2017 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.Evidence synthesis: The search identified 1838 articles. Of those, 36 were included in the evidence synthesis. The majority of the studies identified were retrospective and not controlled. Local recurrence after thermal ablation (TA) may be managed with repeat TA. Alternatively, salvage nephrectomy is possible. However, a higher rate of complications should be expected than after primary nephrectomy. Salvage nephrectomy and TA represent treatment options for local recurrence after partial nephrectomy. Local retroperitoneal recurrence after radical nephrectomy is ideally treated with surgical resection, for which minimally invasive approaches might be applicable to select patients. For large recurrences, addition of intraoperative radiation may improve local control. Local tumour destruction appears to be more beneficial than systemic therapy alone for local recurrences.Conclusions: Management of local renal cancer relapse varies according to the clinical course and prior treatments. The available data are mainly limited to noncontrolled retrospective series. After nephron-sparing treatment, TA represents an effective treatment with low morbidity. For local recurrence after radical nephrectomy, the low-level evidence available suggests superiority of surgical excision relative to systemic therapy or best supportive care. As a consequence, surgery should be prioritised when feasible and applicable.Patient summary: In renal cell cancer, the occurrence and management of local recurrence depend on the initial treatment. This cancer is a disease with a highly variable clinical course. After initial organ-sparing treatment, thermal ablation offers good cancer control and low rates of complications. For recurrence after radical nephrectomy, surgical excision seems to provide the best long-term cancer control and it is superior to medical therapy alone.
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| 3. |
- Scelo, Ghislaine, et al.
(author)
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Genome-wide association study identifies multiple risk loci for renal cell carcinoma.
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10-10), 3p22.1 (rs67311347, P=2.5 × 10-8), 3q26.2 (rs10936602, P=8.8 × 10-9), 8p21.3 (rs2241261, P=5.8 × 10-9), 10q24.33-q25.1 (rs11813268, P=3.9 × 10-8), 11q22.3 (rs74911261, P=2.1 × 10-10) and 14q24.2 (rs4903064, P=2.2 × 10-24). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility.
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| 4. |
- Ouzaid, Idir, et al.
(author)
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Surgical Metastasectomy in Renal Cell Carcinoma : A Systematic Review
- 2019
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In: European Urology Oncology. - : Elsevier. - 2588-9311. ; 2:2, s. 141-149
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Research review (peer-reviewed)abstract
- Context: The benefit of surgical metastasectomy (SM) for patients with metastatic renal cell carcinoma (mRCC) remains controversial because of the lack of high-level evidence on the role of SM in terms of survival benefit in the era of systemic therapy.Objective: To perform a systematic review of the literature on the role of SM in the treatment of mRCC and discuss key issues in the SM decision-making process.Evidence acquisition: A systematic search of the Embase and Medline databases was carried out and a systematic review of the role of SM in mRCC was performed. A total of 56 studies were finally included in the evidence synthesis.Evidence synthesis: All the studies included were retrospective and mostly non-comparative. Median overall survival (OS) ranged from 36 to 142 mo for those undergoing SM, compared to 8-27 mo for no SM. SM was associated with a lower risk of all-cause mortality compared to no SM (pooled adjusted hazard ratio 2.37, 95% confidence interval 2.03-2.87; p < 0.001). Morbidity and mortality were similar for SM and primary tumor surgery. The most important prognostic factor for OS was complete resection of metastases. Other prognostic factors included disease free-survival from nephrectomy, primary tumor features (T stage >= 3, high grade, sarcomatoid features, and pathological nodal status), the number of metastases, and performance status. Lung metastasectomy seemed to show the best survival benefit.Conclusions: Although no randomized clinical data are available, published studies support the role of SM in selected patients in the modern era. Complete SM allows sustained survival free of systemic treatment. Integration of SM and systemic therapy in a multimodal approach remains a valid option for some patients.Patient summary: Surgical resection of metastases originating from renal cell carcinoma may play a role in prolonging survival and avoiding systemic therapy when complete resection is achievable. This strategy is an option for selected patients with a limited number of metastases who still have good general health status.
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