Clinical significance of gene polymorphisms for hereditary predisposition to breast and ovarian cancer (review of literature)

The review presents classical and modern views on the molecular genetic causes underlying hereditary predisposition to breast and ovarian cancer. A computerized literature search was carried out in the electronic databases MEDLINE, Scopus, and Web of Science, published between January 1994 and May 2021, using the keywords: «hereditary breast and ovarian cancer», «BRCA» and «DNA repair». Current views on the role of germline mutations in genes for susceptibility to breast cancer (BC): BRCA1, BRCA2, PALB2, TP53, CHEK2, PTEN, ATM, and PPM1D are presented. The role of a complex of genes involved in homologous DNA repair and causing other hereditary oncological diseases is considered. The role of the loss of heterozygosity in these genes, which increases the level of chromosomal instability and leads to an increased risk of malignant transformation, is considered. Germinal mutations in the genes under consideration in 90% of clinical cases are the cause of initiation of tissue malignancy and greatly increase the risk of developing hereditary breast cancer and OC. The review emphasizes the complex nature of pathogenesis and significant polymorphism of genetic targets for hereditary breast cancer and OC. It is concluded that it is necessary to use NGS panels for complex screening of genes of hereditary susceptibility to these oncological diseases. The review provides data on the clinical significance of each group of genes of hereditary predisposition in the pathogenesis of breast cancer and OC, and also demonstrates the possible role of methylation of the promoter regions of genes and the state of mitochondrial DNA in the development of these pathologies. The purpose of this review was to broaden the horizons of specialists in the field of oncology and clinical diagnostics in the context of the rapidly expanding spectrum of molecular genetic markers of hereditary breast and ovarian cancers.

Lamellar Sclerectomy with Sclerostomy for Choroidal Hemangioma in Sturge-Weber Syndrome: A Case Report

Sturge-Weber syndrome (SWS) is a rare phakomatoses without any hereditary predisposition. The choroidal hemangioma and glaucoma are frequently present on the same side as facial nevus flammeus. We report a case of choroidal hemangioma with glaucoma not responding to medical therapy and managed with four quadrants lamellar sclerectomy with sclerostomy.

Clinical Prognosis of AKT2 and COX2 Mutation on Colorectal Cancer

Cancer has become one of the most mortal diseases in the world. It was estimated in 2018 18.1 millions new cancer cases. The colorectal cancer (CRC) is the third most common type of cancer in men and the second in women around the world [1]. The incidence risk in the occidental population is 5% to 6%, and it can increase to 15% to 30% when a first degree relative has the diagnoses. In hereditary predisposition cancer syndrome like the Lynch syndrome it can grow up to 80% [2].

Gene polymorphisms associated with the remodeling of the connective tissue as markers of preclinical diagnosis of primary open-angle glaucoma in patients with hereditary predisposition

Цель исследования - изучение взаимосвязи полиморфизмов генов, кодирующих структуру регуляторных белков синтеза и деградации экстрацеллюлярного матрикса соединительной ткани, с развитием первичной открытоугольной глаукомы (ПОУГ). Обследовано 144 человека (мужчин - 56, женщин - 88), средний возраст 59,3±6,2, не состоящих в родстве, русской национальности. Группу I составили 40 человек с подозрением на глаукому, в группу II вошли 40 человек с диагнозом ПОУГ I-II стадий на одном или обоих глазах. Пациенты обеих групп имели отягощенный семейный анамнез по глаукоме. Группу контроля составили 64 относительно здоровых человека. Всем пациентам проведены стандартные и специальные офтальмологические, а также молекулярно-генетические исследования. Носительство генотипа GT и аллеля Т полиморфизма rs8136803 (TIMP3), генотипа AG и аллеля A полиморфизма rs652438 (MMP12), генотипа GA и аллеля A полиморфизма rs3825942 (LOXL1) ассоциировано с развитием ПОУГ. Ассоциации полиморфизма rs1048661 гена LOXL1 с развитием ПОУГ не выявлено. Проведенное исследование указывает на необходимость формирования алгоритма обследования пациентов с ПОУГ и подозрением на глаукому с включением молекулярно-генетических исследований. Objective: to study gene polymorphisms associated with the remodeling of the connective tissue of the eye as markers of preclinical diagnosis of primary open-angle glaucoma in patients with hereditary predisposition. Materials and methods: a total of 144 persons (56 men, 88 women), average age 59.3±6.2, were examined, not related, of Russian nationality. Group I consisted of 40 individuals suspected to affected by glaucoma, group II included 40 individuals with a diagnosis of I-II stage POAG in one or both eyes. Patients of both groups had a complicated family history of glaucoma. The control group consisted of 64 relatively healthy individuals. All patients underwent standard and special ophthalmological examination, as well as molecular genetic testing. Results: carriage of GT genotype and T allele of rs8136803 polymorphism (TIMP3), AG genotype and A allele of rs652438 polymorphism (MMP12), GA genotype and A allele of rs3825942 polymorphism (LOXL1) was associated with the development of POAG. The rs1048661 polymorphism of the LOXL1 gene cannot be considered as a marker of POAG development. Conclusion: the study indicates the need to develop a correct algorithm for diagnosing patients with POAG and suspected glaucoma with the inclusion of molecular genetic studies.

Study of the Prevalence of Glaucoma in Kazakhstan

Background Glaucoma is one of the leading causes of permanent visual disability around the world. However, the available literature lacks data on the prevalence of glaucoma in Central Asia, particularly in the Republic of Kazakhstan. Objective The study was aimed at assessing the prevalence of glaucoma in the population of the Republic of Kazakhstan over 40 years old in 2019. Methods A retrospective study was based on the analysis of the results of glaucoma screenings in 171 832 patients over 40 years old living in Kazakhstan (in 14 counties). Glaucoma cases were confirmed by Goldmann tonometry, fundus photography, and visual field testing. Demographic indicators, territorial differences, and hereditary predisposition were studied and analysed. In addition, blood pressure was measured. Results Of 171 832 patients examined, 452 with verified glaucoma were identified. The average age of the patients was 63.9 ± 9.4. In rural areas, the prevalence of glaucoma was higher compared to the urban population. The overall prevalence of glaucoma among people over 40 years old was 2.37 ± 0.17. The prevalence of glaucoma among women was higher than for men, with an indicator of 1.91 (95% CI relative risk 1.78 – 2.03) (p < 0.05). The highest prevalence was found in the 71 – 75 age group [equals to 14.2% (95% CI 11.7 – 19.9)], with a statistically significant difference (p < 0.05). The highest prevalence of glaucoma was observed in the group of people with a hereditary predisposition, with an indicator of 14.7% (95% CI 0.6 – 1.9) (p < 0.05). Among all patients with concomitant arterial hypertension (n = 90, 19.9%), women (60%) compared with men (40%) had a 2.4% higher risk of glaucoma morbidity (95% CI 1.2% − 3.8%). Conclusion This study provides updated information on the prevalence of glaucoma in Kazakhstan. The results obtained confirm that the increase in the prevalence of glaucoma in Kazakhstan is directly proportional to the increase in the patientsʼ age. These results showed the importance of screening for a timely diagnosis, especially for patients with high risk factors such as hereditary predisposition. Moreover, the results indicate that the early detection of systemic hypertension and increased intraocular pressure can be used for the prevention of undesirable outcomes such as an irreversible blindness.