Development Of Kidney Cancer Research Articles

The Interplay between von Hippel-Lindau Tumor Suppressor Gene, Lon Protease, ROS Accumulation, and Inflammation in Clear Cell Renal Cell Carcinoma.

This study explores the role of the von Hippel-Lindau (VHL) tumor suppressor gene and Lon protease in the development of clear cell renal carcinoma (ccRCC) through mechanisms involving inflammation and reactive oxygen species (ROS) accumulation in kidney cells. By examining the impact of VHL on the early stages of kidney cancer development, this research highlights the contributions of inflammation and ROS, as well as the involvement of Lon protease. The findings reveal increased Lon expression and ROS levels in VHL-knockdown HK-2 cells, along with elevated phospho-c-Jun N-terminal kinase (JNK) levels, emphasizing the complex interplay between VHL, Lon protease, inflammation, and ROS in kidney cell models. These insights point to potential therapeutic pathways for ccRCC.

Research progress on the correlation between obesity and the occurrence and development of kidney cancer: a narrative review.

Obesity is an important risk factor for the onset of kidney cancer, and the mechanism of obesity leading to the occurrence and development of kidney cancer has been further studied and confirmed in the past decade. The emergence of the "obesity paradox" phenomenon has made the correlation between obesity and the prognosis of kidney cancer survival controversial. This review summarizes the association between obesity and the occurrence and development of kidney cancer based on newly discovered evidence in the past 10 years, in order to provide reference for follow-up research. A comprehensive, non-systematic review of the latest literature was carried out in order to investigate the progress of the correlation between obesity and kidney cancer. PubMed, Web of Science and Embase were being examined and the last run was on July 15, 2024. The correlation between obesity and the occurrence and development of kidney cancer was discussed in this review, and the newly discovered evidence of epidemiology and related mechanisms in the past 10 years was summarized. The latest evidence suggests that obesity is an important risk factor for the development of kidney cancer. Perirenal fat plays an important role in promoting kidney cancer progression and prognosis. Epidemiology shows that the high rates of kidney cancer and obesity coincide in terms of region and ethnicity. The underlying mechanisms associated with obesity in promoting the occurrence and development of kidney cancer mainly include: abnormal expression of adipocytokines, abnormal lipid metabolism, abnormalities in the insulin-like growth factor-I (IGF-I) axis and hyperinsulinemia/insulin resistance, hypoxia and inflammation. As adipose tissue is adjacent to the kidney, the effect of perirenal adipose tissue on the prognosis of kidney cancer is controversial, and some evidence supports the idea of the "obesity paradox".

Chinese expert consensus on the systemic treatment of advanced clear cell renal cell carcinoma (2024 edition)

Renal cell carcinoma (RCC) accounts for approximately 2% to 3% of malignant tumors in adults, with a male-to-female ratio of approximately 1.5∶1 worldwide. It can occur in all age groups, with a peak incidence in the 60-70 age range, and the median age is approximately 64 years. The current causes of kidney cancer are still unclear, but smoking, obesity, hypertension, and some genetic factors are considered risk factors for kidney cancer development. Conducive to the gradual popularization of physical examination and screening, more and more patients with kidney cancer are being detected and treated in the early stages. However, nearly 30% of patients still have locally advanced or metastatic kidney cancer at the time of initial diagnosis. Traditional chemotherapy drugs are generally ineffective for advanced RCC, and currently, advanced RCC is mainly treated with anti-vascular and immunotherapy. At present, first-line treatment is mostly stratified based on clinical characteristics such as International mRCC Database Consortium (IMDC) prognosis risk, and there are multiple options available, including anti vascular therapy, anti-vascular combined immunotherapy, and dual immunotherapy. Subsequently, first-line treatment often selects drugs based on the composition, effectiveness, and safety of first-line treatment plans. In recent years, research has found that the molecular typing and metastasis characteristics of RCC also affect the prognosis of patients, leading to many controversies in the treatment of advanced RCC. This consensus is guided by the controversial clinical issues in the management of advanced RCC. After discussion and voting by multidisciplinary clinical experts, a consensus of 10 clinical issues has been reached. At the same time, experts recommend domestic clinical and research institutions to lead or participate in more large-scale clinical trials, providing more basis for clinical decision-making and the selection of the best beneficiaries.

Cranial Nerve Palsy and Risk of Kidney Cancer: A Nationwide Population-Based Study.

Background and Objective: Understanding whether cranial nerve palsy (CNP) acts as an independent risk factor for kidney cancer could have important implications for patient care, early detection, and potentially the development of preventive strategies for this type of cancer in individuals with CNP. This study aimed to examine the risk of kidney cancer following the onset of ocular motor CNP and assess whether CNP could be considered an independent risk factor for kidney cancer. Materials and Methods: A population-based cohort study was conducted using data from the National Sample Cohort (NSC) database of Korea's National Health Insurance Service which was collected from 2010 to 2017. Follow-up was until kidney cancer development, death, or 31 December 2018. Cox proportional hazard regression analysis was performed to determine hazard ratios (HRs) for kidney cancer according to CNP status. Participants aged 20 years or more diagnosed with CNP from 2010 to 2017 were included. Exclusions comprised individuals with specific pre-existing conditions, inability to match a control group, and missing data, among others. CNP patients were age-sex matched in a 1:5 ratio with control cases. The primary outcome was incidence of kidney cancer during the follow-up period. Results: This study comprised 118,686 participants: 19,781 in the CNP group, and 98,905 in the control group. Compared to the control group, participants with CNP had a higher risk of kidney cancer (adjusted HR in model 4, 1.599 [95% CI, 1.116-2.29]). After a 3-year lag period, the CNP group had a significantly higher risk (adjusted HR in model 4, 1.987 [95% CI, 1.252-3.154]). Conclusions: Ocular motor CNP may be an independent risk factor for kidney cancer, as indicated by a higher incidence of kidney cancer in CNP patients. Further research is needed to elucidate the underlying mechanisms and explore potential preventive measures for kidney cancer in patients with ocular motor CNP.

Von Hippel-Lindau protein signalling in clear cell renal cell carcinoma.

The distinct pathological and molecular features of kidney cancer in adaptation to oxygen homeostasis render this malignancy an attractive model for investigating hypoxia signalling and potentially developing potent targeted therapies. Hypoxia signalling has a pivotal role in kidney cancer, particularly within the most prevalent subtype, known as renal cell carcinoma (RCC). Hypoxia promotes various crucial pathological processes, such as hypoxia-inducible factor (HIF) activation, angiogenesis, proliferation, metabolic reprogramming and drug resistance, all of which contribute to kidney cancer development, growth or metastasis formation. A substantial portion of kidney cancers, in particular clear cell RCC(ccRCC), are characterized by a loss of function of Von Hippel-Lindautumour suppressor (VHL), leading to the accumulation of HIF proteins, especially HIF2α, a crucial driver of ccRCC. Thus, therapeutic strategies targeting pVHL-HIF signalling have been explored in ccRCC, culminating in the successful development of HIF2α-specific antagonists such as belzutifan (PT2977), an FDA-approved drug to treat VHL-associated diseases including advanced-stage ccRCC. An increased understanding of hypoxia signalling in kidney cancer came from the discovery of novel VHL protein (pVHL) targets, and mechanisms of synthetic lethality with VHL mutations. These breakthroughs can pave the way for the development of innovative and potent combination therapies in kidney cancer.

Research Progress of Metabolic Syndrome and Renal Cancer

Metabolic syndrome (MS) is a condition of metabolic abnormalities in genetically predisposed individuals that are caused by lifestyle habits such as consumption of diet rich in fat and lack of exercise. Few major symptoms include abnormal glucose tolerance, hypertension, abnormal lipid metabolism (including high triglycerides in the blood, low high density lipoprotein cholesterol, etc.), obesity, etc. Although metabolic syndrome has been found to be mainly related to cardiovascular diseases, diabetes, malignancy and other diseases, in recent years, more and more evidence has shown that MS is closely related to the occurrence, development and prognosis of kidney cancer, among which obesity and hypertension have been identified as major risk factors for kidney cancer. This article reviews the research progress on the relationship between MS and its components and the risk, invasiveness, and prognosis of renal carcinoma, so as to provide reference for the prevention, diagnosis, treatment and prognosis of renal cancer.

Exploring the gut microbiome and immunological landscape in kidney cancer: a Mendelian randomization analysis.

Kidney cancer (KC) is a significant health burden globally, with over 400,000 new cases estimated in 2020. The prognosis of KC is influenced by various factors, including tumor spread, pathological characteristics, and molecular genetic changes. Recent studies have emphasized the involvement of gut microbiota and the immune system's contribution in the onset of KC. This extensive research endeavor sought to investigate the potential associations between diverse immune cell phenotypes, specific gut microbiota species, and their impact on the risk of developing KC, alongside the examination of circulating inflammatory proteins. Adhering to the STROBE-MR guidelines, our investigation involved a two-stage Mendelian randomization (2SMR) analysis grounded on three fundamental assumptions: relevance, independence, and exclusion restriction. The exposure data utilized in this study originated from genome-wide association studies (GWAS) specifically designed to explore immune traits, inflammatory proteins, and gut microbiota compositions. Our analysis identified 25 immune phenotypes, 4 circulating inflammatory proteins, and 12 gut microbiota features that exhibited significant causal associations with KC (P < 0.05). 10 immune phenotypes were protective against KC, while 15 were risk factors. Among the inflammatory proteins, CCL28 and IL-2 were protective, whereas FGF-23 and β-NGF were risk factors. Gut microbiota features associated with reduced KC risk included biosynthetic pathways involving amino acids and specific bacterial genera, whereas others, like Butyrivibrio crossotus and Odoribacter splanchnicus, were risk factors. Immune, inflammatory, and gut microbiota factors impact KC development. Identified factors hint at biomarkers and therapeutic targets. It is very important to understand the relationship between these factors and KC.

Associations of dietary patterns with kidney cancer risk, kidney cancer-specific mortality and all-cause mortality among postmenopausal women.

The empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) are novel measures of dietary quality associated with insulin hypersecretion or chronic inflammation, respectively, whereas the Healthy Eating Index (HEI-2015) measures adherence to the Dietary Guidelines for Americans (DGA). We evaluated associations of EDIH, EDIP and HEI-2015 on the risk of both kidney cancer development and mortality. We calculated the dietary scores from baseline food frequency questionnaires among 115,830 participants aged 50-79 years in the Women's Health Initiative. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) for kidney cancer risk, kidney cancer-specific mortality and all-cause mortality, per 1-standard deviation increment in dietary pattern scores. Higher EDIH was associated with greater risk of kidney cancer development [HR, 1.12; 95%CI, (1.01,1.23)], kidney cancer-specific death [1.22(0.99,1.48)], and all-cause mortality, [1.05(1.02,1.08)]. Higher HEI-2015 was associated with lower risk of kidney cancer development, [0.85(0.77, 0.94)], kidney cancer-specific death, [0.84(0.69,1.03)] and all-cause mortality, [0.97(0.95,1.00)]. However, EDIP was not significantly associated with outcomes. Associations did not differ by BMI categories. Low-insulinemic dietary patterns and higher quality diets, are worthy of testing in dietary pattern intervention trials for kidney cancer prevention and improved survivorship.

Comparative Analysis and Drug Target Identification of Human Kidney Cancer

Abstract: Kidney cancer, particularly renal cell carcinoma (RCC), is a significant global health concern characterized by its high morbidity and mortality rates. In this study, we employ a multifaceted approach to gain insights into the molecular mechanisms underlying kidney cancer and to identify potential drug targets for therapeutic intervention. To achieve this, we conducted a comprehensive comparative analysis of gene expression profiles in normal and cancerous kidney tissues, utilizing tools such as BLAST and gene analysis from the COSMIC database. This analysis allowed us to identify key genetic alterations and pathways associated with kidney cancer progression. Furthermore, molecular docking simulations were performed to predict potential drug candidates that could target specific proteins implicated in kidney cancer development. The aim was to prioritize molecules with high binding affinity and therapeutic potential. Additionally, cobalt analysis was utilized to investigate the metalloprotein content within kidney cancer cells, shedding light on potential metalloprotein targets for drug development.The results of this study provide valuable insights into the molecular basis of kidney cancer, offering a foundation for the identification of novel drug targets and the development of targeted therapies for this life-threatening disease. These findings contribute to our understanding of kidney cancer pathogenesis and may ultimately improve patient outcomes and the overall management of this challenging malignancy.

Association of metabolic syndrome and its components with the risk of kidney cancer: A cohort-based case-control study.

Metabolic syndrome increases the risk of developing several types of cancer in humans; however, its effect on the development of kidney cancer is not uniform. To investigate the association between metabolic syndrome (MetS) and its components and the risk of developing kidney cancer. We conducted a cohort-based case-control study. The case group included 217 patients with new kidney cancer in the Kailuan cohort. A total of 868 subjects who were matched for age and sex with those in the case group age (± 1 year) at 1:4 as the control group were selected from baseline survey participants without malignant tumours at the same time as the case group. Biennial baseline survey data of the cases and controls were collected, and the baseline data nearest to the onset time of cases were used for statistical analyses. Logistic proportional risk regression models were used to analyse the association between MetS and its components and the risk of developing kidney cancer. The proportion of MetS patients in the case group was significantly higher than that in the control group (P< 0.01). The risk of developing kidney cancer was significantly higher in the MetS group than in the non-MetS group [odds ratio (OR) (95% confidence interval, CI) = 1.63 (1.20-2.21)], and the risk of kidney cancer increased as the number of MetS components increased compared with subjects without any MetS components (p𝑡𝑟𝑒𝑛𝑑< 0.01). Elevated blood pressure and low high-density lipoprotein cholesterol levels were associated with the risk of kidney cancer [OR (95% CI) = 1.49 (1.02-2.17) and 1.55 (1.13-2.13), respectively]. Our findings suggest that the risk of developing kidney cancer is correlated with MetS.

HF01-05 UKRAINIAN CONTRIBUTIONS TO UROLOGY: AN IMPORTANT REMINDER

You have accessJournal of UrologyCME1 Apr 2023HF01-05 UKRAINIAN CONTRIBUTIONS TO UROLOGY: AN IMPORTANT REMINDER Daniel Nemirovsky, Maksym Pikul, Zoe Blake, Alexander Kenigsberg, Neil Mendrihatta, Peter Pinto, and Gennady Bratslavsky Daniel NemirovskyDaniel Nemirovsky More articles by this author , Maksym PikulMaksym Pikul More articles by this author , Zoe BlakeZoe Blake More articles by this author , Alexander KenigsbergAlexander Kenigsberg More articles by this author , Neil MendrihattaNeil Mendrihatta More articles by this author , Peter PintoPeter Pinto More articles by this author , and Gennady BratslavskyGennady Bratslavsky More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003243.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Over the past year, the world has witnessed acts of unprovoked violence and aggression in Ukraine. The AUA issued a strong statement standing against the atrocities and inhumanity of war. Many urologists, both with and without ties to Ukraine, have shown support to the country in various ways. In this light, it is imperative to not only support its citizens, but also to remember the contributions Ukraine has had on our understanding of urology. METHODS: Data was obtained with review of both PubMed and non-PubMed indexed literature, as well as through personal interviews with leading urologists in Ukraine. RESULTS: In the field of genitourinary reconstruction, the first ever use of oral mucosa in urethroplasty was pioneered by Kirill Sapezhko in the late 19th century, while working in Kyiv. Interestingly, Dr. Sapezhko was also the first recorded surgeon to describe a two-stage urethroplasty, using a method now known as the Thiersch-Duplay technique. Ludwik Rydygier, as head of the University of Lviv (then Lemberg), developed an early method for transperineal simple prostatectomy, as well as innovating several techniques for repair of vesicovaginal fistulae in the late 1800s. Yurii Voronoy, while working in Kherson during the early 20th century, revolutionized transplantation by conducting the first recorded renal allotransplant, as well as studying the various stages of immunologic rejection. In the mid-to-late 1900s, urologic oncologists in Kharkiv, including Boris Polonsky, Alexey Pereverzev, and Viktor Karpenko, conducted valuable research describing innovative techniques for IVC thrombectomy. More recently, Ukrainian scientists have made enormous strides in our understanding of urologic carcinogenesis, in large part due to the devastating Chernobyl disaster and related chronic ionizing radiation exposure. These studies have led to better insight into the development of kidney and bladder cancers, including the description of ionizing-radiation induced carcinoma in situ, termed “Chernobyl Cystitis”. CONCLUSIONS: Ukrainian urologists have made significant impacts to the field, with important and novel studies spanning across many urologic subspecialties. As urologists, one of the ways that we can support Ukraine is to highlight their many contributions to the field. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e257 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daniel Nemirovsky More articles by this author Maksym Pikul More articles by this author Zoe Blake More articles by this author Alexander Kenigsberg More articles by this author Neil Mendrihatta More articles by this author Peter Pinto More articles by this author Gennady Bratslavsky More articles by this author Expand All Advertisement PDF downloadLoading ...

Development of genomic instability-associated long non-coding RNA signature: A prognostic risk model of clear cell renal cell carcinoma.

Renal clear cell carcinoma (ccRCC) is the most lethal of all pathological subtypes of renal cell carcinoma (RCC). Genomic instability was recently reported to be related to the occurrence and development of kidney cancer. The biological roles of long non-coding RNAs (lncRNAs) in tumorigenesis have been increasingly valued, and various lncRNAs were found to be oncogenes or cancer suppressors. Herein, we identified a novel genomic instability-associated lncRNA (GILncs) model for ccRCC patients to predict the overall survival (OS). The Cancer Genome Atlas (TCGA) database was utilized to obtain full transcriptome data, somatic mutation profiles, and clinical characteristics. The differentially expressed lncRNAs between the genome-unstable-like group (GU) and the genome-stable-like group (GS) were defined as GILncs, with |logFC| > 1 and an adjusted p-value< 0.05 for a false discovery rate. All samples were allocated into GU-like or GS-like types based on the expression of GILncs observed using hierarchical cluster analyses. A genomic instability-associated lncRNA signature (GILncSig) was constructed using parameters of the included lncRNAs. Quantitative real-time PCR analysis was used to detect the in vitro expression of the included lncRNAs. Validation of the risk model was performed by the log-rank test, time-dependent receiver operating characteristic (ROC) curves analysis, and multivariate Cox regression analysis. Forty-six lncRNAs were identified as GILncs. LINC00460, AL139351.1, and AC156455.1 were employed for GILncSig calculation based on the results of Cox analysis. GILncSig was confirmed as an independent predictor for OS of ccRCC patients. Additionally, it presented a higher efficiency and accuracy than other RCC prognostic models reported before. GILncSig score was qualified as a critical indicator, independent of other clinical factors, for prognostic prediction of ccRCC patients.

Analysis of expression pattern of proteins associated with AKT/mTOR signaling pathway in kidney cancer development

Introduction: The purpose of this study was to analyze the expression status, reciprocal interplay, and prognostic significance of AKT1 and hypoxia-inducible factor 1 alpha (HIF-1α) in AKT/mechanistic target of the rapamycin pathway and to enable them to be studied as possible therapeutic targets. Materials and Methods: This prospective study included 25 patients with clear cell renal cell carcinoma (ccRCC) operated between December 2019 and January 2022. Tumor and adjacent normal tissue samples were subjected to immunohistochemical analysis, RNA extraction, cDNA synthesis, and quantitative real-time polymerase chain reaction for AKT and HIF-1α. The fold changes were then calculated by ∆∆Ct method. Results: The included 25 ccRCC patients had 1.5-fold greater HIF-1 mRNA expression and 0.9-fold higher AKT1 gene expression in the ccRCC tissues compared to the corresponding healthy control. High, moderate, and low expression of HIF-1α was seen in 15, 6, and 1 of 25 samples, respectively. High, moderate, and low expression of p-AKT1 was seen in 18, 2, and 3 of 25 samples, respectively. Conclusion: Our study data predicted higher gene expression as well as protein expression of HIF-1α and AKT. The proteins HIF-1α and AKT are localized in the nucleus of the RCC tumor samples compared to normal. Overexpression of these proteins might play significant roles in tumor development and differentiation as reported by others previously. This study can help clarify the biological role of HIF-1α and AKT in RCC to develop new strategies for this malignancy.

Phytochemicals for the Prevention and Treatment of Renal Cell Carcinoma: Preclinical and Clinical Evidence and Molecular Mechanisms.

Simple SummaryRenal cell carcinoma (RCC) is the most frequently diagnosed kidney cancer. Once RCC metastasizes, successful treatment is difficult to achieve. There is an apparent need for novel approaches to prevent and treat RCC. Phytochemicals are naturally derived compounds gaining increasing scientific interest due to their cancer preventive and chemotherapeutic properties. These phytochemicals have been shown to exhibit a multitude of anticancer effects against RCC. In this systematic review, we critically evaluate the potential these natural compounds possess for the prevention and treatment of RCC and discuss the future implications this may have in the fight against kidney cancer.Renal cell carcinoma (RCC) is associated with about 90% of renal malignancies, and its incidence is increasing globally. Plant-derived compounds have gained significant attention in the scientific community for their preventative and therapeutic effects on cancer. To evaluate the anticancer potential of phytocompounds for RCC, we compiled a comprehensive and systematic review of the available literature. Our work was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. The literature search was performed using scholarly databases such as PubMed, Scopus, and ScienceDirect and keywords such as renal cell carcinoma, phytochemicals, cancer, tumor, proliferation, apoptosis, prevention, treatment, in vitro, in vivo, and clinical studies. Based on in vitro results, various phytochemicals, such as phenolics, terpenoids, alkaloids, and sulfur-containing compounds, suppressed cell viability, proliferation and growth, showed cytotoxic activity, inhibited invasion and migration, and enhanced the efficacy of chemotherapeutic drugs in RCC. In various animal tumor models, phytochemicals suppressed renal tumor growth, reduced tumor size, and hindered angiogenesis and metastasis. The relevant antineoplastic mechanisms involved upregulation of caspases, reduction in cyclin activity, induction of cell cycle arrest and apoptosis via modulation of a plethora of cell signaling pathways. Clinical studies demonstrated a reduced risk for the development of kidney cancer and enhancement of the efficacy of chemotherapeutic drugs. Both preclinical and clinical studies displayed significant promise of utilizing phytochemicals for the prevention and treatment of RCC. Further research, confirming the mechanisms and regulatory pathways, along with randomized controlled trials, are needed to establish the use of phytochemicals in clinical practice.

The current state of genetic risk models for the development of kidney cancer: a review and validation.

To review the current state of genetic risk models for predicting the development of kidney cancer, by identifying and comparing the performance of published models. Risk models were identified from a recent systematic review and the Cancer-PRS web directory. A narrative synthesis of the models, previous validation studies and related genome-wide association studies (GWAS) was carried out. The discrimination and calibration of the identified models was then assessed and compared in the UK Biobank (UKB) cohort (cases, 452; controls, 487 925). A total of 39 genetic models predicting the development of kidney cancer were identified and 31 were validated in the UKB. Several of the genetic-only models (seven of 25) and most of the mixed genetic-phenotypic models (five of six) had some discriminatory ability (area under the receiver operating characteristic curve >0.5) in this cohort. In general, models containing a larger number of genetic variants identified in GWAS performed better than models containing a small number of variants associated with known causal pathways. However, the performance of the included models was consistently poorer than genetic risk models for other cancers. Although there is potential for genetic models to identify those at highest risk of developing kidney cancer, their performance is poorer than the best genetic risk models for other cancers. This may be due to the comparatively small number of genetic variants associated with kidney cancer identified in GWAS to date. The development of improved genetic risk models for kidney cancer is dependent on the identification of more variants associated with this disease. Whether these will have utility within future kidney cancer screening pathways is yet to determined.

Relationship of TP53 gene with retroelements in urogenital organs carcinogenesis

The article presents a hypothesis about the influence of TP53 gene on the development of prostate, kidney, and bladder cancer through negative regulation of retrotransposons. The p53 protein is a transcription factor that controls the expression of various protein-coding genes. The promoter regions of endogenous retroviruses contain almost ideal binding sites for p53, which suppresses translation of these elements and LINE1s. The TP53 gene contains retrotransposons, which promote mutations due to recombinations. Germinal mutations of the TP53 gene in Li–Fraumeni syndrome cause a deficiency of the p53 protein, which leads to the activation of retroelements, which, in turn, cause loss of heterozygosity of the second TP53 allele. The result is a “vicious circle” that stimulates genomic instability and carcinogenesis. This mechanism is possible for sporadic urogenital system malignant neoplasms development, where TP53 mutations are most often identified, acting as drivers of carcinogenesis. At the same time, pathological activation of retroelements is found in many malignant neoplasms. Moreover, the “vicious circle”, when a deficiency of an oncosuppressor causes activation of retroelements that contribute to inactivation of other oncosuppressors, is characteristic not only for р53. Retroelements can be controlled by other oncosuppressor genes that contain hot spots of insertional mutagenesis and retrotransposons (which contribute to recombination events). I suppose that pathological interregulation of retroelements and tumor suppressors is a universal mechanism of carcinogenesis in the development of sporadic malignant neoplasms and hereditary tumor syndromes. Chromoplexy observed in 90 % of prostate cancer samples may reflect these events, since activated retroelements in carcinogenesis contribute to complex chromosomal rearrangements.

Germline BRCA1 and BRCA2 mutations and the risk of bladder or kidney cancer in Poland

IntroductionThe role of the BRCA1 and BRCA2 genes in bladder and renal tumorigenesis is unclear. Our goal was to determine the prevalence of specific founder mutations genes BRCA1 (5328 insC, C61G and 4153 delA) and BRCA2 (C5972T) mutations in bladder and kidney cancer patients from Poland.Materials and methodsWe genotyped 1028 patients with bladder cancer and 688 cases with kidney cancer and two control groups.ResultsA BRCA1 mutation (all variants combined) was detected in peripheral blood leukocytes in 5 out of 1028 (0.5%) bladder cases and in 17 of 4000 controls (0.4%) (odds ratio [OR], (OR = 1.1; 95% CI 0.42–3.11; p = 1.0). Among 688 unselected kidney cancer cases a BRCA1 mutations was reported in three patients (0.4%) (OR = 1.0; 95% CI 0.29–3.51; p = 1.0). The mutation C5972T in BRCA2 was observed in 54 bladder cancer patients (5.2%) and in 159 of 2791 healthy controls (5.7%) (OR = 0.9; 95% CI 0.66–1.26; p = 0.6). Fifty kidney cancer cases carried a BRCA2 mutation (7.3%) (OR = 1.3; 95% CI 0.93–1.80; p = 0.1).ConclusionIn conclusion, we found no difference in the prevalence of BRCA1 and BRCA2 founder mutations between cases and healthy controls. The mutations BRCA1 and BRCA2 seem not to play a role in bladder and kidney cancer development in Polish patients.

Association Between Diabetes and the Risk of Kidney Cancer: Systematic Review and Meta-Analysis.

Diabetes is a risk factor for several types of cancer, but the specific relationship between diabetes and kidney cancer is not well understood. We conducted a search strategy in scientific databases for case-control and cohort studies on this topic. We analyzed 17 studies and found that diabetes was significantly associated with the risk of developing kidney cancer and that this risk was slightly stronger for women and for people living in Asia. These findings were not influenced by obesity, cigarette smoking, or hypertension. We conclude that diabetes is an independent risk factor for the development of kidney cancer.

Long-term oncological results of surgical treatment of localized renal tumors

Objective: to analyze the long-term oncological results of surgical treatment of patients with stage cT1-сТ2аN0M0 renal cell cancer.Materials and methods. The analysis included 326 patients who underwent partial nephrectomy (PN) in 210 (64.42 %) and radical nephrectomy (RN) - in 116 (35.58 %). Stage cT1a tumors were found in 129 (39.57 %), cT1b - in 149 (45.71 %), cT2a - in 48 (14.72 %) cases. PN and RN for cT1a was performed in 113 (53.81 %) and 16 (13.79 %), for cT1b -in 86 (40.95 %) and 63 (54.31 %), for cT2a - in 11 (5.24 %) and 37 (31.90 %) patients. We used open approach in 5 (1.53 %), laparoscopic in 148 (45.26 %) and robotic in 173 (53.21 %). The median follow-up was 49.9 [26.0; 81.4] months.Results. In the group of patients with stage cT1a disease, 4 recurrences of the tumor process were revealed (3 local recurrences after PN and 1 after RN). Seven deaths were recorded (4 after PR and 3 after RN). Two deaths occurred due to the progression of kidney cancer (1 after PN and 1 after RN). 5-year disease-free survival after PN and RN was 95.93 ± 2.32 % versus 92.31 ± 7.39 % (p &gt;0.05); 5-year overall survival - 96.48 ± 2.08 % versus 85.56 ± 9.65 % (p &gt;0.05); 5-year cancer-specific survival - 98.33 ± 1.65 % versus 92.25 ± 6.5 % (p &gt;0.05).In the group of patients with stage cT1b disease, 12 recurrences were revealed (5 after PN and 7 after RN). 14 deaths were recorded (4 after PN and 10 after RN). Four deaths were related to the development of kidney cancer (all after RN). 5-year disease-free survival after PN and RN was 92.97 ± 3.1 % versus 86.99 ± 4.64 % (p &gt;0.05); 5-year overall survival -95.1 ± 2.78 % versus 88.63 ± 4.4 % (p &gt;0.05); 5-year cancer-specific survival - 100 % versus 94.1 ± 3.33 % (p &gt;0,05).There were no recurrences of the oncological process or deaths after PN in the group of patients with the stage of cT2a disease during four years of follow-up. After RN six recurrences of the oncological process, four deaths (3 of them due to the progression of kidney cancer) were recorded. Thus, the disease-free survival at was 80.57 ± 7.15 %; overall survival - 90.28 ± 5.34 %; cancer-specific survival - 93.63 ± 4.37 %.Conclusion. PN is the priority treatment for renal cell cancer. Oncological results of nephron-sparing surgery are superior to the results of RN, however, these differences are not reliable and require a longer study.

Germline HOXB13 mutation p.G84E do not confer an increased bladder or kidney cancer risk in polish population

IntroductionThe role of HOXB13 in bladder and renal tumorigenesis is unclear. Our goal was to determine the prevalence of HOXB13 p.G84E mutation in bladder and kidney cancer patients from Poland.Materials and methods1418 patients with bladder cancer and 813 cases with kidney cancer and 4497 controls were genotyped for HOXB13 p.G84E.Resultsp.G84E mutation of HOXB13 gene was detected in three of 1418 (0.2%) bladder cancer cases and in six of 4497 controls (odds ratio [OR], 1.6; 95% CI 0.39–6.36; p = 0.8). Among 813 kidney cancer cases HOXB13 mutations was reported in three patients (0,4%) (odds ratio [OR], (OR = 2,8; 95% CI 0.69–11.11; p = 0.3). In cases with mutations in the HOXB13 gene, the family history of cancer was negative.ConclusionHOXB13 mutation was not associated with bladder or kidney cancer. Mutation p.G84E in HOXB13 seem not to play a role in bladder and kidney cancer development in Polish patients.