Рак предстательной железы представляет собой серьезную клиническую и социальную проблему. Патоморфоз заболевания, появление новых методов терапии, высокое экономическое бремя, связанное как с инновационностью лечения, так и с увеличивающейся распространенностью заболевания, требуют перспективного планирования ресурсов системы здравоохранения. К настоящему времени сформированы организационные инструменты, позволяющие накапливать определенные эпидемиологические и клинические данные о заболевании. Таким инструментом является Белорусский канцер-регистр. Потребность в данных для выполнения оценки внедрения новых медицинских технологий в онкологии, в частности при ведении пациентов с раком предстательной железы, требует понимания организационных возможностей обеспечения системой здравоохранения доступности этих технологий для пациентов. Цель. Сбор и анализ эпидемиологических данных о пациентах с раком предстательной железы, определение группы пациентов с неметастатическим кастрационно- резистентным раком предстательной железы на основе данных Белорусского канцер-регистра. Материалы и методы. При выполнении исследования использовались эпидемиологические и статистические методы. Результаты. Белорусский канцер-регистр является наиболее полным информационным ресурсом данных о новых и ранее зарегистрированных случаях злокачественных новообразований на территории страны. Сведения о пациентах, включенных в регистр, позволяют в автоматическом режиме определить количество пациентов с неметастатическим кастрационно-резистентным раком предстательной железы. Корректное внесение данных в первичную медицинскую документацию обеспечивает раннюю постановку диагноза с возможностью достижения значимых показателей выживаемости. Выводы. Данные, накопленные в Белорусском канцер-регистре, а также результаты международных эпидемиологических и клинических исследований позволяют своевременно определять категорию пациентов с нмКРРПЖ для продления и улучшения качества их жизни. Purpose. To collect and analyse epidemiological data on patients with PCa, to determine the group of patients with nmCRPC based on data from the Belarusian Cancer Registry (BCR) [State Institution Republican Scientific and Practical Centre of Oncology and Medical Radiology named after N.N. Aleksandrov] and to determine the group of patients with nmCRPC based on data from the Belarusian Cancer Registry (BCR). N.N. Alexandrov. Department of the Belarusian Cancer Registry. Electronic access: https://omr.by/o-nas/ otdeleniya/vse-otdelenya/otdelenie-kantser-registra. Methods. Epidemiological and statistical methods were used in the study. Results. The CDB is the most comprehensive information resource of data on new and previously reported cases of malignant neoplasms on the territory of the country. Data on patients included in the registry allow automatic determination of the number of patients with nmCRPC. Correct entry of data into the primary medical records ensures early diagnosis with the possibility of achieving meaningful survival rates. Conclusions. The data accumulated in the BRC, as well as the results of international epidemiological and clinical studies, allow timely identification of a category of patients with nmRCC to prolong and improve their quality of life.

Цель. Проанализировать онкологические последствия проведения нестандартного лечения пациентов с герминогенным раком яичка для разработки мер по улучшению качества лечения. Материалы и методы. В исследование включены пациенты (n=253), получившие лечение или консультативную помощь в нашем учреждении с 2010 по 2015 г. включительно по поводу герминогенных опухолей яичка. Пациентов с клинически или морфологически несеминомным раком было 134 (53%), с семиномой – 119 (47%). Медиана возраста пациентов составила 32 года. Выживаемость определялась по методу Каплана – Мейера, значимость различий оценивалась по критериям log-rank и хи-квадрат. Ассоциация нарушений стандартов лечения с риском прогрессирования, смерти от рака или смерти от любых причин определялась с использованием моновариантного и мультивариантного анализа пропорциональных рисков Кокса. Все значения p были двухсторонними, за статистически значимый уровень различий принималось p<0,05. Результаты. Нарушения стандартов лечения выявлены у 144 (56,9%) пациентов, у 101 (39,9%) – по 1 нарушению, у 43 (17,0%) – по несколько нарушений. Риск прогрессирования рака яичка после проведения лечения в 5,6 раза (95% доверительный интервал (ДИ) 3,1–9,9, р<0,001) выше при неудалении остаточных образований после химиотерапии >1 см, в 3,2 (95% ДИ 1,55–6,51, р=0,002) раза выше при недостаточном количестве курсов химиотерапии, в 4,1 (2,4–7,0, р<0,001) раза при любом виде недостаточного лечения и в 2,0 (1,1–3,6, р=0,019) раза – при нарушении стандартов лечения. Риск смерти после проведения лечения пациентов с герминогенными опухолями яичка в 8,5 раза (95% ДИ 4,3–17,1, р<0,001) выше при неудалении остаточных образований после химиотерапии >1 см, в 5,2 (95% ДИ 2,4–11,6, р<0,001) раза выше при недостаточном количестве курсов химиотерапии, в 7,1 (3,5–14,1, р<0,001) раза – при любом виде недостаточного лечения и в 2,5 (1,2–5,3, р=0,019) раза – при нарушении стандартов лечения. Выводы. На отдаленные результаты лечения пациентов с герминогенным раком яичка наиболее существенно, клинически и статистически значимо влияет проведение недостаточного лечения, при котором 5-летняя выживаемость до прогрессирования составляет 52,2% (стандартная ошибка (SE) 7,4%) против 80,8% (SE 4,1%) (р<0,001), 5-летняя общая выживаемость – 60,7% (SE 7,2%) против 89,2% (SE 3,2%) (р<0,001). При неудалении остаточных опухолей после химиотерапии 5-летняя ВБП составляет 36,7% (SE 9,3%) против 79,7% (SE 3,8%) (р<0,001), 5-летняя ОВ – 47,9% (SE 9,7%) против 87,5% (SE 3,1%) (р<0,001). Purpose. To analyze the oncological consequences of non-guideline concordant treatment in patients with germ-cell testicular cancer. Materials and methods. The study included patients with testicular germ cell tumors (n=253) who received treatment or counseling at our institution from 2010 to 2015. There were 134 (53%) patients with nonseminoma clinically or pathologically and 119 (47%) with seminoma. The median age of patients was 32 years. Survival was calculated by the Kaplan – Meier method, the statistical differences was assessed by log-rank and chi-square tests. The association of non-guideline concordant treatment components with the risk of progression, death from cancer or death from any cause was determined using monovariate and multivariate Cox proportional hazards analysis. All p-values were two-tailed, with p<0.05 taken as a statistically significant level for the difference. Results. Non-guideline concordant treatment was detected in 144 (56.9%) patients, in 101 (39.9%) one and in 43 (17.0%) several components of therapy violations were detected. The risk of testicular cancer progression was 5.6 (95% confidence interval (CI) 3.1–9.9, p<0.001) times higher if residual tumors >1 cm were not removed after chemotherapy, and 3.2 (95% CI 1.55–6.51, p=0.002) times higher with insufficient number of chemotherapy courses, 4.1 (2.4–7.0, p<0.001) times higher with any type of insufficient treatment and 2.0 (1.1–3.6, p=0.019) times higher in case of any insufficient therapy. The risk of death after treatment was 8.5 (95% CI 4.3–17.1, p<0.001) times is higher in patients with non-removal of residual tumors >1 cm after chemotherapy, 5.2 (95% CI 2.4–11.6, p<0.001) times higher with insufficient number of chemotherapy courses, 7.1 (3.5–14.1, p<0.001) times higher with any type of insufficient treatment and 2.5 (1.2–5.3, p=0.019) times higher in case of violation of treatment standards. Conclusion. The long-term results of the treatment in patients with testicular germ-cell cancer clinically and statistically significantly affected by undertreatment with 5-year progression-free survival (PFS) 52.2% (standard error (SE) 7.4%) versus 80.8% (SE 4.1%) (p<0.001) and 5-year overall survival (OS) 60.7% (SE 7.2%) vs 89.2% (SE 3.2%) (p<0.001). If residual tumors are not removed after chemotherapy, the 5-year PFS was 36.7% (SE 9.3%) vs. 79.7% (SE 3.8%) (p<0.001) and 5-year OS was 47.9% (SE 9.7%) vs. 87.5% (SE 3.1%) (p<0.001).

В статье представлен обзор литературы, посвященный современным аспектам диагностики рака мочевого пузыря (РМП), включающей неинвазивные (цитология мочи, маркеры мочи, компьютерная томография (КТ), мультипараметрическая магнитно-резонансная томография (мпМРТ)) и инвазивные методы исследования (цистоскопия, трансуретральная резекция (ТУР)), а также показана роль мпМРТ в оценке эффективности неоадъювантной химиотерапии. The article presents a review of the literature on modern aspects of the diagnosis of bladder cancer (BCa), including non-invasive (urine cytology, urine markers, computed tomography (CT), multiparametric magnetic resonance imaging (mpMRI)) and invasive research methods (cystoscopy, transurethral resection (TUR)), as well as the role of mpMRI in evaluating the effectiveness of neoadjuvant chemotherapy.

Context: Our prior systematic review and meta-analysis of individual participant data (IPD) suggesting a benefit of adjuvant chemotherapy for muscle-invasive bladder cancer was limited by the number and size of included randomised trials. We have updated results to include additional trials, providing the most up-to-date and reliable evidence of the effects of this treatment. Objective: To investigate the role of adjuvant cisplatin-based chemotherapy in the treatment of muscle-invasive bladder cancer. Evidence acquisition: Published and unpublished trials were sought via searches of bibliographic databases, trials registers, conference proceedings, and hand searching. Updated IPD were centrally collected, checked, and analysed. Results from individual randomised controlled trials (RCTs) were combined using a two-stage fixed-effect model. Prespecified analyses explored any variation in effect by trial and participant characteristics. Evidence synthesis: Analyses of ten RCTs (1183 participants) demonstrated a benefit of cisplatin-based adjuvant chemotherapy on overall survival (hazard ratio [HR] = 0.82, 95% confidence interval [CI] = 0.70-0.96, p = 0.02). This represents an absolute improvement in survival of 6% at 5 yr, from 50% to 56%, and a 9% absolute benefit when adjusted for age, sex, pT stage, and pN category (HR = 0.77, 95% CI = 0.65-0.92, p = 0.004). There was no clear evidence that the effect varied by trial or participant characteristics. Adjuvant chemotherapy was also shown to improve recurrence-free survival (HR = 0.71, 95% CI = 0.60-0.83, p < 0.001), locoregional recurrence-free survival (HR = 0.68, 95% CI = 0. 55-0.85, p < 0.001), and metastasis-free survival (HR = 0.79, 95% CI = 0.65-0.95, p = 0.01), with absolute benefits of 11%, 11%, and 8%, respectively. Conclusions: This systematic review and meta-analysis demonstrates that cisplatinbased adjuvant chemotherapy is a valid option for improving outcomes for muscleinvasive bladder cancer. Patient summary: We looked at the effect of cisplatin-based chemotherapy on outcomes in participants with muscle-invasive bladder cancer. We gathered this information from eligible randomised controlled trials. We demonstrated that cisplatin-based chemother- apy is a valid option for improving outcomes of muscle-invasive bladder cancer. (c) 2021 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).

PURPOSESince the development of the International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification in a 1997 study, high-income countries have reported a significant increase in survival for poor prognosis patients. There are scant data on IGCCCG risk-stratified survival from low- and middle-income countries. We assessed the progression-free survival (PFS) and overall survival (OS) rates in a contemporary cohort of Belarusian patients with advanced germ cell cancer (GCC) stratified by the IGCCCG prognostic classification and analyzed prognostic factors for survival.MATERIALS AND METHODSThe consecutive cohort of patients with clinical stage IIb-III testicular GCC or extragonadal germ cell tumors who received treatment or consultation in our two centers between 2010 and 2015 was included. All patients underwent primary chemotherapy. The patients were divided into seminoma and nonseminomatous germ cell carcinoma (NSGCC) subgroups. The Kaplan-Meier method was used to estimate 5-year PFS and OS.RESULTSThis study included 111 patients with a median age of 32 years, 95% of whom were diagnosed with testicular cancer. Seminoma and NSGCC were identified in 32 (29%) and 79 (71%) patients, respectively. The median follow-up was 6.1 years. The 5-year PFS and OS rates for the entire cohort were 70% and 77%, respectively. In patients with good prognosis seminoma and good, intermediate, and poor prognosis NSGCC, the estimated PFS rates were 76%, 88%, 74%, and 39% and those for OS were 83%, 97%, 83%, and 38%, respectively.CONCLUSIONIn our cohort of Belarusian patients with advanced germ cell tumors, we failed to demonstrate an improvement in PFS and OS compared with the 1997 IGCCCG study. Moreover, survival in poor prognosis group is inferior to that in IGCCCG and all contemporary series from high-income countries.

Abstract Background Real‐world data describing outcomes of treatment among metastatic renal cell carcinoma (mRCC) patients are limited and heterogeneous. Aim RENSUR3 registry study assessed real‐world data on the use of therapies in mRCC and overall survival (OS) in Russia, Kazakhstan, and Belarus. Methods Patients were included in the retrospective multicenter registry study. To be eligible, patients were required to have mRCC diagnosed from January 2015 to January 2016. Anonymized data were collected through an online registry. The outcomes of interest were patient characteristics, treatment patterns, and OS. Results 1094 mRCC patients were identified. Mean age was 62.3 (SD, 11.2) years. Four hundred and forty‐four (41%) patients were 65 years and older. Primary tumor has not been removed in 503 (46%) patients. Subtype of RCC based on WHO classification (clear‐cell or other) has been reported in 402 (37%) patients. In total, 595 (54.4%) patients received systemic therapy for metastatic disease. 58% of elderly patients (≥65) were not treated compared to 37% of younger patients. Cytokines and targeted therapy were used in 298 (50.1%) and 297 (49.9%) of 595 treated patients, respectively. Median OS was 11.9 months (95% CI 10.9‐12.9). The 1‐ and 3‐year OS rates were 49.6% and 19.3%. Conclusions Half of patients received no systemic therapy or had only cytokines for mRCC in Russia, Kazakhstan, and Belarus, which doubtless negatively affected OS in this population. Novel therapies should be considered as life prolonging and a priority.

INTRODUCTION:This study assesses the efficacy and tolerability of two cycles of adjuvant chemotherapy (AC) with gemcitabine and cisplatin after radical cystectomy in patients with a high risk of progression of muscle-invasive urothelial bladder cancer as compared to chemotherapy at relapse, in a prospective randomized study.MATERIAL AND METHODS:From 2008 to 2013, all patients after radical cystectomy at our institution for primary or recurrent urothelial bladder cancer with stage pT3-4 and/or pN+ on histopathology and without contraindications to combination cisplatin-based chemotherapy, were randomized either to two cycles of gemcitabine and cisplatin chemotherapy or to follow-up and chemotherapy at the time of relapse. The study endpoints were overall, cancer-specific, and disease-free survival.RESULTS:The study included 100 patients, of whom 53 received AC and the other 47 were assigned to the control arm. Out of 53 allocated to AC arm, 16 patients did not start chemotherapy or received only one cycle of AC. The median follow-up for patients in the AC and control arms was 88 and 86 months, respectively. In the AC arm the hazard ratio for death from any cause, death from bladder cancer, and disease relapse were 0.70 (95% CI 0.45-1.11; p = 0.13), 0.84 (95% CI 0.50-1.41; p = 0.51), and 0.77 (95% CI 0.46-1.28; p = 0.31), respectively.CONCLUSIONS:Two cycles of AC with gemcitabine and cisplatin in patients with high-risk urothelial bladder cancer after radical cystectomy does not improve overall, cancer-specific, and disease-free survival. Only 53% of patients randomized to AC received the entire planned treatment.

INTRODUCTION:This paper aims to evaluate the influence of quality of transurethral resection in patients with non-muscle invasive bladder cancer on the benefit of fluorescent cystoscopy-assisted transurethral resection in the post hoc analysis of the single-center randomized controlled trial.MATERIAL AND METHODS:We retrospectively analyzed the results of the prospective randomized study assessing the efficacy of fluorescent cystoscopy-assisted transurethral resection. The quality of transurethral resection was defined on the basis of a separate retrospective study estimating the variability in recurrence risk for the individual surgeon. The subgroup analysis of fluorescent cystoscopy-assisted transurethral resection efficacy depending on surgical experience was performed.RESULTS:Of 377 eligible patients, transurethral resection was performed in 365 (97%) by surgeons with available grading information. Two 'experienced' surgeons performed 238 (63%) of all transurethral resections and three 'less experienced' surgeons completed 127 (34%) surgeries. The two surgical groups were comparable with respect to basic prognostic factors and subsequent therapy. The median follow-up was 56 months.In the total cohort of patients, fluorescent cystoscopy significantly decreased the risk of recurrence with hazard ratio 0.58 (p = 0.004). In the 'experienced surgeons' subgroup the benefit of fluorescent cystoscopy was not significant (hazard ratio 0.81, p = 0.34), whereas the 'less experienced' subgroup showed a marked difference in favor of fluorescent cystoscopy-assisted transurethral resection (hazard ratio 0.31, p = 0.001), with a P-value for interaction of 0.021.CONCLUSIONS:Baseline quality of surgery may be a significant interacting factor affecting the magnitude of the benefit of fluorescent cystoscopy-assisted transurethral resection in patients with non-muscle invasive bladder cancer.

INTRODUCTION:The objective of this study was to assess recent trends in incidence, mortality and relative survival (RS) in testicular cancer (TC) patients in Belarus and to provide international comparisons of our figures.MATERIAL AND METHODS:We surveyed the Belarusian Cancer Registry for all male cases diagnosed with International Classification of Diseases for Oncology, third edition (ICD-O-3) topography code C62 between 1990 and 2015. Trends for incidence and mortality rates per 100,000 of the world standard population and annual percentage changes (APCs) were calculated. We also estimated the 1- and 5-year RS rates for the 1990-1998, 1999-2007 and 2008-2015 periods according to the Ederer II method. The RS estimates for the 2008-2015 period were age-standardized and compared with the published EUROCARE-5 data and SEER-18 database analysis.RESULTS:A total of 2,500 and 2,439 cases were included into incidence and survival analyses, respectively. We found a significant increase in the TC age-standardized incidence rate (APC 2.6%) and a decline in the age-standardized mortality (APC -3.0%) over the study period. RS significantly increased in all patients` strata; a relative increase was more pronounced in advanced stages of seminoma and younger age groups. Nevertheless, the most recent figures of age-standardized RS including stage-specific estimates were generally worse than the European and SEER data.CONCLUSIONS:We have found a significant increase in TC incidence in Belarus in recent years. Mortality has significantly declined with a corresponding increase in RS which, however, did not reach European or North American figures. Continued effort is required to improve the quality of management of TC patients in our country.

e23033 Background: Russia, Belarus and Kazakhstan are countries of the Eurasian Economic Union with upper-middle-income economies. Limited sources of the healthcare system could affect the treatment of individual cancer patients. The data on the treatment outcomes of elderly patients with mRCC are limited in these countries. RENSUR3 registry study assessed real-world data on the use of therapies in mRCC and overall survival (OS) in this population. Methods: Patients from Russia, Belarus and Kazakhstan were included in the retrospective multicenter registry study. To be eligible, patients were required to have mRCC diagnosed from January 2015 to January 2016. Anonymized data were collected through an online registry. The outcomes of interest were OS, patient characteristics and treatment patterns. Results: 1,094 adult mRCC patients were identified. Mean age at diagnosis of mRCC was 62.3 (SD, 11.2) years. 447 (41%) patients were 65 years and older. In total, 595 (54.4%) patients received systemic therapy for metastatic disease. 58% of elderly patients were not treated compared to 37% of younger patients. Cytokines were the most commonly used treatment in elderly patients (115 of 189 patients, 61%) while targeted therapy was more widely used in younger patients (223 of 406, 55%). Median OS was 12.7 months (95% CI 11.3-14.1) and 9.3 months (7.7-9.9) for patients aged < 65 and ≥65 years, respectively (P < 0.0001). Conclusions: More than half of elderly patients received no systemic therapy or had only cytokines for mRCC in Russia, Belarus and Kazakhstan which doubtless negatively affected OS in this population. Novel therapies should be considered as life-saving and a priority in elderly patients.

Aim. To determine the influence of the polymorphic variants of the base (OGG1 and XRCC1) and nucleotide (ERRC2/XPD and ERRC6/CSB) excision repair genes on the mutational and epigenetic status of bladder tumors. Methods. For this study, we used previously obtained data on the polymorphism of DNA repair genes in bladder cancer (BC) patients, whose tumor tissue samples were analyzed for the presence of key mutational and epigenetic changes. Results. Genotypes containing at least one minor OGG1 rs1052133 allele were significantly associated with an increased frequency of RAS family gene mutations and a reduced frequency of PIK3CA mutations. The polymorphisms of both base excision repair genes influenced the epigenetic variability of urothelial carcinomas, the modifying effect of OGG1 rs1052133 manifesting in ISL1 methylation and XRCC1 rs25487 impacting p16 or TIMP3 methylation. The minor ERRC6/CSB rs2228526 allele was associated with RAS mutations and lack of TIMP3 methylation. Likewise, carriers of the genotypes containing at least one minor ERRC2/XPD rs1799793 allele were less frequently found to have methylated RUNX3 gene in tumor tissues. Conclusions. The polymorphisms of the base (OGG1, XRCC1) and nucleotide (ERRC2/XPD, ERRC6/CSB) excision repair genes modify the mutational and epigenetic variability of a number of key BC genes. The study of the mechanisms of such interactions is necessary for understanding the molecular basis of BC pathogenesis. Keywords: bladder cancer, OGG1, XRCC1, ERRC2/XPD, ERRC6/CSB gene polymorphism, mutation, methylation.

AIM Base excision repair (BER) gene polymorphisms are known to play an independent role in predisposition to developing different cancers as well as to be associated with clinicopathological traits of the disease modifying its clinical outcomes. One of the underlying mechanisms is presumed to include interplay between BER gene polymorphisms and key mutational, epigenetic and chromosomal events in tumor tissues. The present study was aimed at elucidating potential gene-gene interaction and assessing their mutual effects in bladder cancer (BC). MATERIALS AND METHODS The earlier obtained data on genotyping patients with verified diagnosis of BC for OGG1 rs1052133 (Ser326Cys) and XRCC1 rs25487 (Arg399Gln) polymorphisms were used for this study. The tumor tissue samples from the same patients were analyzed for mutations, epigenetic variations and losses of heterozygosity in some key genes involved in divergent pathogenic pathways of BC. RESULTS It was shown that the OGG1 (326 codon) heterozygous genotype as well as the minor 326Cys allele can intensify a mutational response of the RAS locus in urothelial carcinomas in the total cohort of patients simultaneously decreasing the mutation rates in the PIK3CA locus in smokers. The XRCC1 (399 codon) heterozygous genotype as well as the minor 399Gln allele reduced the frequency of LOH in the PTEN and TNKS genes, but did not affect the mutational variability in any locus tested. Both polymorphisms influenced the methylation status, carriers of OGG1 326Ser/Cys or Ser/Cys+Cys/Cys genotypes demonstrating increased frequency of methylated RUNX3 and ISL1 genes whereas the similar effect of XRCC1 polymorphism concerning methylation of p16 and TIMP3 genes. When dividing the total cohort into groups based on the extent of tumor spread, the observed associations were characteristic of non-muscle invasive BC. CONCLUSION The BER gene polymorphisms contributed to modification of key molecular events in urothelial carcinomas. Their mutual effects mainly manifested in non-muscle invasive BC. The underlying mechanisms as well as possible clinical outcomes need to be further explored to propose novel prognostic biomarkers for BC.

Рак мочевого пузыря (РМП) занимает 9 место в мире среди всех злокачественных новообразований и является второй по частоте опухолью в онкоурологической практике.Ежегодно в мире регистрируется более 430 тыс.новых случаев, Резюме.Мышечно-инвазивный рак мочевого пузыря (МИРМП) с неблагоприятным прогнозом (категории рТ3-4N0 либо pN+) характеризуется высокой агрессивностью течения опухолевого процесса и смертностью.В настоящее время в рамках комплексного лечения данной патологии наряду с радикальной цистэктомией (ЦЭ) используется неоадъювантная (НХТ) либо адъювантная химиотерапия (АХТ), главным образом, на основе цисплатина, характеризующаяся высокой токсичностью и умеренной эффективностью.У пациентов с МИРМП с неблагоприятным прогнозом, которым не проводилась НХТ, после радикальной ЦЭ предлагается применять режимы M-VAC (цисплатин, адриамицин, метотрексат и винбластин), GC (гемцитабин, цисплатин) или CMV (цисплатин, метотрексат и винбластин).Данные исследований, в том числе и проспективного рандомизированного исследования, проведенного в Республиканском научно-практическом центре онкологии и медицинской радиологии им.Н.Н.Александрова, показали, что наибольшая эффективность АХТ отмечается в подгруппе пациентов без метастатического поражения регионарных лимфоузлов.

BACKGROUND:DNA helicases maintain genome stability, and their deficiency is associated with disorders resembling premature aging as well as contributes to carcinogenesis. Their functions are determined by the respective genes encoding nucleotide excision repair initiating proteins, e.g. XPD and CSB. OBJECTIVE:The present study aimed to investigate the influence of genetic variations in ERCC2/XPD (rs1799793, rs13181) and ERCC6/CSB (rs2228526, rs2228528) loci on lifespan and developing age-related bladder cancer focusing on homozygous wild type alleles. METHOD:The allelic variants were identified in 354 clinically healthy controls and 418 bladder cancer patients using the PCR-RFLP method. RESULTS:The age-depended increase in frequencies of homozygous carriers of wild-type XPD 312Asp and XPD 751Lys alleles was observed among controls, especially among subjects over 80 years (r = 0.67, p = 0.012). The statistically significant correlation was also found between the frequency of homozygous wild type alleles at all tested loci and age in healthy population over 60 years (r = 0.35, p = 0.046) suggesting the relationship between lifespan and longevity, on one hand, and normal functioning of these genes and their products, on the other hand. Homozygous carriers of wild type alleles were less susceptible to bladder cancer, tumor invasion, increase in grade of malignancy and recurrence, but their effects were specific with respect to clinicopathological and lifestyle characteristics. CONCLUSION:Homozygous wild type alleles encoding XPD and CSB proteins with optimal properties were shown to affect human lifespan, risk of developing bladder cancer, its progression and recurrence under certain conditions.

Background: DNA helicases maintain genome stability, and their deficiency is associated with disorders resembling premature aging as well as contributes to carcinogenesis. Their functions are determined by the respective genes encoding nucleotide excision repair initiating proteins, e.g. XPD and CSB. Objective: The present study aimed to investigate the influence of genetic variations in ERCC2/XPD (rs1799793, rs13181) and ERCC6/CSB (rs2228526, rs2228528) loci on lifespan and developing age-related bladder cancer focusing on homozygous wild type alleles. Method: The allelic variants were identified in 354 clinically healthy controls and 418 bladder cancer patients using the PCR-RFLP method. Results: The age-depended increase in frequencies of homozygous carriers of wild-type XPD 312Asp and XPD 751Lys alleles was observed among controls, especially among subjects over 80 years (r = 0.67, p = 0.012). The statistically significant correlation was also found between the frequency of homozygous wild type alleles at all tested loci and age in healthy population over 60 years (r = 0.35, p = 0.046) suggesting the relationship between lifespan and longevity, on one hand, and normal functioning of these genes and their products, on the other hand. Homozygous carriers of wild type alleles were less susceptible to bladder cancer, tumor invasion, increase in grade of malignancy and recurrence, but their effects were specific with respect to clinicopathological and lifestyle characteristics. Conclusion: Homozygous wild type alleles encoding XPD and CSB proteins with optimal properties were shown to affect human lifespan, risk of developing bladder cancer, its progression and recurrence under certain conditions. Keywords: ERCC2/XPD, ERCC6/CSB, SNP, DNA helicase, lifespan, longevity, bladder cancer.