MUTATIONS OF GENES BRCA1 AND BRCA2 IN WOMEN WITH OVARIAN CANCER EXPOSED TO FACTORS OF CHORNOBYL NUCLEAR ACCIDENT
| Autor: | L A Rybchenko, Larysa Poluben, G M Bychkova, S V Klymenko, G V Stephanovych |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
medicine.medical_specialty Gene Expression Gene mutation medicine.disease_cause Gastroenterology Germline mutation Gene Frequency Mutation Rate Statistical significance Internal medicine medicine Humans Radiology Nuclear Medicine and imaging Longitudinal Studies Mutation frequency Allele skin and connective tissue diseases Alleles Germ-Line Mutation Aged BRCA2 Protein Ovarian Neoplasms Mutation BRCA1 Protein business.industry Incidence (epidemiology) Middle Aged Radiation Exposure Chernobyl Nuclear Accident Case-Control Studies Cohort Female Ukraine business |
| Zdroj: | Проблеми радіаційної медицини та радіобіології = Problems of Radiation Medicine and Radiobiology. 24:455-464 |
| ISSN: | 2313-4607 2304-8336 |
| Popis: | to determine a frequency of germline mutations 185delAG, 5382insC in BRCA1 gene and 6174delT in BRCA2 gene in Ukrainian patients with OC including women who were exposed to the factors of Chornobyl nuclear accident.In the study we enrolled 306 OC patients of different age who were tested for the presence of the major BRCA1 and BRCA2 gene mutations using allele specific multiplex polymerase chain reaction.The mutation frequency in patients exposed to IR with OC (main group) was 5.3 % (2 from 38). Among unexposed patients (control group) 11,2 % (30 from 268) of cases with mutation were identified. However, the dif- ference between the groups was not significant (p = 0.39). It was shown that the BRCA1/2 mutations frequency in the patient of both groups was 10,4 % (32 from 306). The mutation BRCA1 5382insC was positive in 87.5 % (28 from 32) of cases, nevertheless nobody was identified with the allelic variant BRCA2 6174delT among both groups. There was a tendency toward an earlier age of the OC manifestation in the patients exposed to IR due to Chornobyl nuclear accident compared to BRCA-positive women of the control group (р = 0.06). When comparing BRCA-positive and BRCA-negative patients with OC of the main group, there was a statistical significance regarding the earlier age of the disease manifestation in the patients with mutations (р = 0.04). However, such difference was not observed in the control group (р = 0.22).The frequency of the mutations in exposed to IR and unexposed patients with OC does not differ and depends on a spectrum of studied BRCA1/2 gene mutations, level of DNA amplification and sample number. The allel- ic variant BRCA1 5382insC is dominant and accounts for 87.5 % of the total number of the found mutations. Due to the radiation factor the OC in the BRCA1-positive individuals is realized at the earlier age than in patients negative for these mutations. The incidence of OC after the Chornobyl accident was observed 27-38 years later in a cohort of women who were from 4 to 40 years old at the moment of the nuclear explosion.Meta: vstanovyty chastotu germinal'nykh mutatsiy̆ 185delAG, 5382insC gena BRCA1 i 6174delT gena BRCA2 u khvorykh na rak iaiechnykiv (RIa) v Ukraïni, zokrema u zhinok, iaki zaznaly vplyvu chynnykiv Chornobyl's'koï katastrofy. Materialy i metody. U doslidzhennia vkliucheno 306 khvorykh na RIa riznogo viku, iakym bulo provedeno molekuliar- no-genetychne vyznachennia mazhornykh mutatsiy̆ v genakh BRCA1 i BRCA2 za dopomogoiu alel'-spetsyfichnoï mul'typle- ksnoï polimeraznoï reaktsiï.Rezul'taty. Chastota mutatsiy̆ u khvorykh na RIa z radiatsiy̆nym anamnezom (osnovna grupa) sklala 5,3 % (2 z 38). U khvorykh bez radiatsiy̆nogo anamnezu (kontrol'na grupa) vyiavleno 11,2 % (30 z 268) vypadkiv z mutatsiieiu. Prote znachushchoï riznytsi v chastoti mutatsiy̆ mizh grupamy khvorykh vyiavleno ne bulo (p = 0,39). Vstanovleno, shcho chastota mu- tatsiy̆ BRCA1/2 u patsiientiv obokh grup sklala 10,4 % (32 iz 306). Na doliu mutatsiï 5382insC u geni BRCA1 prypadaie 87,5 % (28 z 32) vypadkiv z mutatsiieiu, natomist' alel'nyy̆ variant 6174delT gena BRCA2 ne vyiavleno u zhodnoï patsiientky obokh grup. Vyiavleno tendentsiiu do bil'sh rann'ogo viku zakhvoriuvannia na RIa u postrazhdalykh vnaslidok avariï na ChAES z mutatsiiamy porivniano z BRCA-pozytyvnymy osobamy kontrol'noï grupy (r = 0,06). Pry porivnianni khvorykh z BRCA-pozytyvnym RIa ta BRCA-negatyvnym RIa osnovnoï kogorty vstanovleno statystychnu zna- chushchist' shchodo manifestatsiï zakhvoriuvannia u patsiientiv z mutatsiiamy v bil'sh rann'omu vitsi (r = 0,04). Odnak takykh vidminnostey̆ ne sposterigalosia v kontrol'niy̆ grupi (r = 0,22).Vysnovky. Chastota mutatsiy̆ u khvorykh na RIa z radiatsiy̆nym anamnezom i bez takogo ne vidrizniaiet'sia ta zalezhyt' vid spektru doslidzhuvanykh mutatsiy̆ u genakh BRCA1/2, vid stupenia amplifikatsiï DNK i chysel'nosti vybirky. Alel'- nyy̆ variant 5382insC u geni BRCA1 ie dominuiuchym i stanovyt' 87,5 % vid zagal'noï kil'kosti znay̆denykh mutatsiy̆. Cherez diiu radiatsiy̆nogo faktora zakhvoriuvannia na RIa u BRCA1-pozytyvnykh osib realizuiet'sia u bil'sh rann'omu vitsi, nizh u patsiientiv bez mutatsiy̆. Zakhvoriuvanist' na RIa sposterigalas' til'ky cherez 27–38 rokiv pislia Chorno- byl's'koï katastrofy u kogorti zhinok, iakym na moment avariï bulo vid 4 do 40 rokiv. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|