scholarly journals Hereditary cancer syndromes: a modern paradigm

2020 ◽  
Vol 66 (4) ◽  
pp. 24-34
Author(s):  
Elena E. Baranova ◽  
Natalia A. Bodunova ◽  
Мaria V. Vorontsova ◽  
Galina S. Zakharova ◽  
Maria V. Makarova ◽  
...  

About 5–10% of malignant neoplasms (MN) are hereditary. Carriers of mutations associated with hereditary tumor syndromes (HTS) are at high risk of developing tumors in childhood and young age and synchronous and metachronous multiple tumors. At the same time, this group of diseases remains mainly an oncological problem, and clinical decisions are made only when MNs are detected in carriers of pathogenic mutations.Individual recommendations for cancer screening, treatment, and prevention should be developed for carriers of mutations associated with HTS to prevent an adverse outcome of the disease. It is essential to identify patients at risk by doctors of all specialties for further referral to medical and genetic counseling with molecular genetic testing (in case of indications). The problems of standardization of enrollment criteria for genetic tests, further tactics of prevention, screening, and treatment of many hereditary oncological diseases remain unsolved.This review was created to inform doctors of various specialties, including endocrinologists, about the HTS. This allows them to get acquainted with main clinical features of specific syndromes, helps to understand the difference between hereditary and non-hereditary cancer, recognize signs of hereditary cancer, and introduce the indications for genetic examination and genetic counseling of the patient. Also, significant differences between international and domestic recommendations on screening measures, diagnosis, and treatment of HTS underline the need to review the existing and develop new algorithms for medical support of patients with HTS.

Cancer ◽  
1999 ◽  
Vol 86 (S11) ◽  
pp. 2449-2456 ◽  
Author(s):  
Henry T. Lynch ◽  
Patrice Watson ◽  
Trudy G. Shaw ◽  
Jane F. Lynch ◽  
Anne E. Harty ◽  
...  

Cancer ◽  
1999 ◽  
Vol 86 (S8) ◽  
pp. 1629-1636 ◽  
Author(s):  
Henry T. Lynch ◽  
Patrice Watson ◽  
Trudy G. Shaw ◽  
Jane F. Lynch ◽  
Anne E. Harty ◽  
...  

Cancer ◽  
1999 ◽  
Vol 86 (S8) ◽  
pp. 1637-1643 ◽  
Author(s):  
Henry T. Lynch ◽  
Patrice Watson ◽  
Trudy G. Shaw ◽  
Jane F. Lynch ◽  
Anne E. Harty ◽  
...  

Cancer ◽  
1999 ◽  
Vol 86 (S11) ◽  
pp. 2457-2463 ◽  
Author(s):  
Henry T. Lynch ◽  
Patrice Watson ◽  
Trudy G. Shaw ◽  
Jane F. Lynch ◽  
Anne E. Harty ◽  
...  

2017 ◽  
pp. 132-138
Author(s):  
O.V. Paliychuk ◽  
◽  
L.Z. Polishchuk ◽  
Z.I. Rossokha ◽  
◽  
...  

The objective: determining gene polymorphism features ERS1, CYP2D6 in patients with breast cancer (RHZ) and endometrial cancer (EC) and the impact assessment studied genetic characteristics compared to receptor status (immunohistochemical determination of expression levels of ER, PR) tumors and the results of the treatment. Patients and methods. article presents the results of complex clinical, morphological, clinical-genealogical, and molecular-genetic examination of 28 females: 19 patients with breast cancer (BC), 9 patients with endometrial cancer (EC), including 5 patients with primary-multiple tumors (PMT) with and without tumor pathology aggregation in families. Results. The It was determined that in patients’ families malignant tumors of breast, uterine body and/or ovaries prevail that corresponds to Lynch type II syndrome (family cancer syndrome). Molecular-genetic examination of genomic DNA of peripheral blood and histological sections for the presence of SNPs of ESR and CYP2D6*4 genes comparing with the results of immunohistochemical study of tumors for receptors ER and PR status have not found associations between these characteristics; although among EC patients the occurrence of genotypes 397ТТ and 351АА was significantly higher comparing with BC patients (55.55% and 10.5% for genotype 397ТТ,and 15.8% for genotype 351АА, respectively). At the same time the patients with BC and primary-multiple tumors (PMT) of female reproductive system organs (FRSO) that carried mutations in BRCA1 in all the cases demonstrated positive ER and PR receptor status and adverse combinations of polymorphous variants of the genes ESR1 (397СС, 397ТС) and CYP2D6*4 (1846G, 1846GA), suggesting combined effect of these factors on the development of malignant neoplasias of FRSO in families with positive family cancer history. In BC patients, receiving standard hormone therapy with tamoxifen, those, who had genotype 1846GG of the gene CYP2D6*4, in 3 patients (15.8%) of 19 (100%) patients disease recurrence was diagnosed. Conclusion. The obtained results allow clinical use of the assessment of polymorphism frequency of the genes ESR1 and CYP2D6*4 for selection of individual hormone therapy regimens schemes for BC patients, to increase efficacy of dispensary observation after finishing of special therapy for such patients, and also personalization of complex and combined treatment regimens. Key words: breast cancer, endometrial cancer, family cancer syndrome, single nucleotide polymorphisms (SNPs) of the genes ESR1, CYP2D6*4.


2020 ◽  
Vol 24 (4) ◽  
pp. 108-118
Author(s):  
A. V. Petraikin ◽  
A. K. Smorchkova ◽  
N. D. Kudryavtsev ◽  
K. A. Sergunova ◽  
Z. R. Artyukova ◽  
...  

Rationale. Quantitative CT (QCT) bone densitometry with asynchronous calibration not require a phantom during the scan procedure. Based on calibration data it converts X-ray density in HU to bone mineral density (BMD). Given the large number of CT studies performed on patients at risk of osteoporosis, there is a need for a hands-on method capable of assessing BMD in a short period of time without tailored software or protocols.Goal. To develop a method for QCT bone densitometry using an PHK (PHantom Kalium), to compare the volume BMD measurements with the QCT data with asynchronous calibration provided by software from a reputable developer.Methods. The studies were performed at 64-slice CT unit with body scanning parameters. The BMD was measured using two techniques: 1) QCT with asynchronous calibration using software from a reputable developer; 2) QCT using a PHK phantom (QCT-PHK). For convert the HU to BMD values, we scanned the PHK phantom and calculate correction factor. Phantom contains “vertebrae” filled with potassium hydrogen phosphate in different concentrations. In both methods, the BMD values measured for LI–II, and sometimes for ThXII, LIII.Results. The study enrolled 65 subjects (11 male and 54 female patients); median age 69.0 years. A comparison of the vertebrae BMD measured by QCT and QCT-PHK revealed a significant linear Pearson correlation r = 0.977 (p < 0.05). The Bland–Altman analysis demonstrated a lack of relationship between the difference in measurements and the average BMD and a systematic BMD; bias of +4.50 mg/ml in QCT vs. QCT-PHK. Differences in the division into groups osteoporosis / osteopenia / norm according to the ACR criteria for the two methods were not significant.Conclusion. The developed asynchronous QCT-PHK method measure BMD comparable to the widely used QCT with asynchronous calibration. This method can be used for opportunistic screening for osteoporosis.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Alessio Coi ◽  
◽  
Simone Barsotti ◽  
Michele Santoro ◽  
Fabio Almerigogna ◽  
...  

Abstract Background Systemic Sclerosis (SSc) is a chronic autoimmune disease with a complex pathogenesis that includes vascular injury, abnormal immune activation, and tissue fibrosis. We provided a complete epidemiological characterization of SSc in the Tuscany region (Italy), considering prevalence and incidence, survival, comorbidities and drug prescriptions, by using a multi-database population-based approach. Cases of SSc diagnosed between 1st January 2003 and 31st December 2017 among residents in Tuscany were collected from the population-based Rare Diseases Registry of Tuscany. All cases were linked to regional health and demographic databases to obtain information about vital statistics, principal causes of hospitalization, complications and comorbidities, and drug prescriptions. Results The prevalence of SSc in Tuscany population resulted to be 22.2 per 100,000, with the highest prevalence observed for the cases aged ≥ 65 years (33.2 per 100,000, CI 95% 29.6–37.3). In females, SSc was predominant (86.7% on the total) with an overall sex ratio F/M of 6.5. Nevertheless, males presented a more severe disease, with a lower survival and significant differences in respiratory complications and metabolic comorbidities. Complications and comorbidities such as pulmonary involvement (HR = 1.66, CI 95% 1.17–2.35), congestive heart failure (HR = 2.76, CI 95% 1.80–4.25), subarachnoid and intracerebral haemorrhage (HR = 2.33, CI 95% 1.21–4.48) and malignant neoplasms (HR = 1.63, CI 95% 1.06–2.52), were significantly associated to a lower survival, also after adjustment for age, sex and other SSc-related complications. Disease-modifying antirheumatic drugs, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors were the drugs with the more increasing prevalence of use in the 2008–2017 period. Conclusions The multi-database approach is important in the investigation of rare diseases where it is often difficult to provide accurate epidemiological indicators. A population-based registry can be exploited in synergy with health databases, to provide evidence related to disease outcomes and therapies and to assess the burden of disease, relying on a large cohort of cases. Building an integrated archive of data from multiple databases linking a cohort of patients to their comorbidities, clinical outcomes and survival, is important both in terms of treatment and prevention.


2021 ◽  
pp. 43-54
Author(s):  
Antonina G. Baykova ◽  
Marina Yuryevna Vostroknutova ◽  
Natalia A. Ostryakova ◽  
Tatyana Mikhailovna Kiryushina

The aim of the study was to conduct a comparative analysis of spirometric indicators of respiration in various phenotypes of occupational bronchial asthma. Materials and methods. At the clinical stage of the work, a comprehensive clinical, radiological, spirographic, echocardiographic, immunological and molecular genetic examination of 170 patients of the main groups and 50 individuals of the control group was carried out. The results of the study. Dynamic determination of the speed indicators of forced exhalation in various phenotypes of occupational bronchial asthma can improve the diagnosis of obstructive disorders in this pathology, optimize the choice of treatment tactics, and predict the course of this pathology.


2021 ◽  
pp. 125-133
Author(s):  
Г.Ю. Спотарь ◽  
С.А. Блинова ◽  
А.А. Шварцев ◽  
Я.И. Алексеев ◽  
С.М. Гориславец

С помощью молекулярно-генетических и ампелографических методов проведена идентификация сортов винограда, относящихся к наиболее распространенным в мире техническим сортам западно-европейского происхождения. Генотипирование образцов проводилось с использованием 9-ядерных и 3-хлоропластных микросателлитных маркеров. На основании полученных профилей, по данным базы VIVC было установлено, что образец № 2 является сортом Каберне-Совиньон, образец № 4 - сортом Рисланер. Профиль образца № 1 совпадает с профилем сорта Мерло, за исключением разницы в двух парах нуклеотидов (п.н.) в одном аллеле локуса VVMD27, что можно объяснить редким случаем мутации в микросателлитной последовательности и не является достаточным основанием утверждать, что образец № 1 и Мерло являются разными сортами. Генетические профили образцов № 3 и № 6 соответствовали сортам сортогруппы Темпранильо, № 5 - сортам сортогруппы Рислинг рейнский, №7 - сортам сортогруппы Пино черный. Сорта в сортогруппах, полученные в результате соматических мутаций (связанных в основном с окраской ягод), имели одинаковый профиль. Принадлежность образцов к указанным сортам в сортогруппах была подтверждена ампелографическим методом. Использование для идентификации сортов в сортогруппах 6-9-ти SSR-маркеров в сочетании с ампелографическими методами позволяет получить достоверные результаты без удорожания работ. Однако дифференциация клонов и сортов, полученных в результате соматических мутаций, только SSR-маркерами потребует значительного увеличения их количества на 1-2 порядка либо использования высоковариабельных SSR-маркеров, таких как VRG ( Vitis riparia Götzhof). Таким образом, целесообразен более целенаправленный поиск полиморфизмов непосредственно в генах, отвечающих за определенные хозяйственно ценные признаки. В случае возникновения отличия в окраске ягод для дифференциации возможно использовать полиморфизм локуса гена VvMybA1, при изменении во вкусе и аромате ягод - в локусе гена VviDXS, при изменении лигнификации семян - в локусе гена VviAGL11, при повышении устойчивости к заболеваниям - в локусах соответствующих генов резистентности. The identification of grapes related to the most widespread wine varieties of West-European origin was carried out using molecular-genetic and ampelographic methods. Genotyping of samples was provided using 9- nuclear and 3-chloroplast microsatellite markers. Basing on the profiles obtained according to the VIVC database, it was established that Sample No. 2 is a ‘Cabernet-Sauvignon’ variety, and Sample No. 4 is a ‘Rieslaner’ variety. The profile of Sample No. 1 coincides with the ‘Merlot’ profile, except for the difference in 2 base pairs (bp) in one allele of the VVMD27 locus, which can be explained by a rare case of mutation in microsatellite sequence, and is not a sufficient reason to insist that Sample No. 1 and the ‘Merlot’ are different varieties. The genetic profiles of Samples No. 3 and No. 6 corresponded to the varieties of ‘Tempranillo’ group, No. 5 - to the varieties of ‘Rhein Riesling’ group, and No. 7 - to the varieties of ‘Pinot Noir’ group. The varieties of the groups, obtained as a result of somatic mutations (mainly associated with color of berries), had the same profile. The ampelographic method confirmed the origin of samples in the mentioned groups of varieties. Using of 6-9-SSR-markers in combination with ampelographic methods to identify the varieties of groups allows obtaining reliable results without increasing the cost of work. However, differentiation of clones and varieties in groups with only SSR-markers will require a significant increase in their number by 1-2 orders, or using of highly variable SSR-markers, such as VRG ( Vitis riparia Götzhof). Thus, a more targeted search for polymorphisms directly in genes responsible for certain economically valuable traits is advisable. In case of occurrence a difference in the color of berries, it is possible to use for differentiation the polymorphism of VvMybA1 gene locus, when flavor and aroma of berries change - to use the VviDXS gene locus, when seed lignification changes - the VviAGL11 gene locus, when disease resistance increases - the loci of the corresponding resistance genes.


Author(s):  
V. B. Denisenko ◽  
E. M. Simovanyan

Relevance. The study of the etiological structure, clinical features of congenital infections and the immune status of children with perinatal HIV contact will help to improve the program for the diagnosis, treatment and prevention of these diseases.Objective. To characterize the clinical features of congenital infections and changes in the immune system in children with perinatal HIV contact, taking into account their HIV status.Methods. A clinical, serological, molecular genetic, cytological, immunological examination of 203 children with perinatal HIV contact, including 91 HIV-positive patients and 112 HIV-negative patients.Results. Congenital infections were diagnosed in 43.3% of children with perinatal HIV contact. They were characterized by a predominance of cytomegalovirus (30%) and Chlamydia trachomatis (14.3%) in the etiological structure; those infections proceeded as a mono-infection (61.4%) or in a localized form (52.5%). In the group of HIV-positive children, congenital infections developed in 68.1% of patients. In most cases congenital infections were caused by cytomegalovirus (45.1%), herpes simplex virus (6.6%) and bacteria (11%); they proceeded as an associated infection (46.8%), and in a clinically manifest localized (61.3%) and generalized forms (33.9%). The clinical features of congenital infections in HIV-infected children were associated with more significant disorders in the immune system, especially in T-cell link.Conclusion. The revealed clinical and immunological features of congenital infections in children with perinatal HIV contact must be considered during diagnostic, therapeutic and preventive procedures.


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