1. Genetic counselling, BRCA1/2 status and clinico-pathologic characteristics of patients with ovarian cancer before 50 years of ageMirjam Cvelbar, Marko Hočevar, Srdjan Novaković, Vida Stegel, Andraž Perhavec, Mateja Krajc, 2017, izvirni znanstveni članek Povzetek: In Slovenia like in other countries, till recently, personal history of epithelial ovarian cancer (EOC) has not been included among indications for genetic counselling. Recent studies reported up to 17% rate of germinal BRCA1/2 mutation (gBRCA1/2m) within the age group under 50 years at diagnosis. The original aim of this study was to invite to the genetic counselling still living patients with EOC under 45 years, to offer gBRCA1/2m testing and to perform analysis of gBRCA1/2m rate and of clinico-pathologic characteristics. Later, we added also the data of previously genetically tested patients with EOC aged 45 to 49 years. Patients and methods. All clinical data have to be interpreted in the light of many changes happened in the field of EOC just in the last few years: new hystology stage classification (FIGO), new hystology types and differentiation grades classification, new therapeutic possibilities (PARP inhibitors available, also in Slovenia) and new guidelines for genetic counselling of EOC patients (National Comprehensive Cancer Network, NCCN), together with next-generation sequencing possibilities. Results. Compliance rate at the invitation was 43.1%. In the group of 27 invited or previously tested patients with EOC diagnosed before the age of 45 years, five gBRCA1/2 mutations were found. The gBRCA1/2m detection rate within the group was 18.5%. There were 4 gBRCA1 and 1 gBRCA2 mutations detected. In the extended group of 42 tested patients with EOC diagnosed before the age of 50 years, 14 gBRCA1/2 mutations were found. The gBRCA1/2m detection rate within this extended, partially selected group was 33.3%. There were 11 gBRCA1 and 3 gBRCA2 mutations detected. Conclusions. The rate of gBRCA1/2 mutation in tested unselected EOC patients under the age of 50 years was higher than 10%, namely 18.5%. Considering also a direct therapeuthic benefit of PARP inhibitors for BRCA positive patients, there is a double reason to offer genetic testing to all EOC patients younger than 50 years. Regarding clinical data, it is important to perform their re-interpretation in everyday clinical practice, because this may influence therapeutic possibilities to be offered.
Ključne besede: ovarian cancer, BRCA 1/2, genetic counseling
Objavljeno v DiRROS: 24.05.2024; Ogledov: 85; Prenosov: 32
 Celotno besedilo (513,68 KB) |
2. Breast cancer risk prediction using Tyrer-Cuzick algorithm with an 18-SNPs polygenic risk score in a European population with below-average breast cancer incidenceTjaša Oblak, Petra Škerl, Benjamin J. Narang, Rok Blagus, Mateja Krajc, Srdjan Novaković, Janez Žgajnar, 2023, izvirni znanstveni članek Povzetek: Goals: To determine whether an 18 single nucleotide polymorphisms (SNPs) polygenic risk score (PRS18) improves breast cancer (BC) risk prediction for women at above-average risk of BC, aged 40-49, in a Central European population with BC incidence below EU average. Methods: 502 women aged 40-49 years at the time of BC diagnosis completed a questionnaire on BC risk factors (as per Tyrer-Cuzick algorithm) with data known at age 40 and before BC diagnosis. Blood samples were collected for DNA isolation. 250 DNA samples from healthy women aged 50 served as a control cohort. 18 BC-associated SNPs were genotyped in both groups and PRS18 was calculated. The predictive power of PRS18 to detect BC was evaluated using a ROC curve. 10-year BC risk was calculated using the Tyrer-Cuzick algorithm adapted to the Slovenian incidence rate (S-IBIS): first based on questionnaire-based risk factors and, second, including PRS18. Results: The AUC for PRS18 was 0.613 (95 % CI 0.570-0.657). 83.3 % of women were classified at above-average risk for BC with S-IBIS without PRS18 and 80.7 % when PRS18 was included. Conclusion: BC risk prediction models and SNPs panels should not be automatically used in clinical practice in different populations without prior population-based validation. In our population the addition of an 18SNPs PRS to questionnaire-based risk factors in the Tyrer-Cuzick algorithm in general did not improve BC risk stratification, however, some improvements were observed at higher BC risk scores and could be valuable in distinguishing women at intermediate and high risk of BC.
Ključne besede: early breast cancer, polygenic risk score, risk prediction
Objavljeno v DiRROS: 21.03.2024; Ogledov: 145; Prenosov: 40
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6. Dedni rak telesa maternice : kdaj je indicirano genetsko svetovanjeKsenija Strojnik, Ana Blatnik, Mateja Krajc, 2023, objavljeni znanstveni prispevek na konferenci Povzetek: Tudi genetski dejavniki imajo vlogo pri nagnjenosti k razvoju raka telesa maternice. Najpogosteje se pojavlja v sklopu dednega sindroma Lynch (približno 3 % vseh bolnic z rakom telesa maternice). Pri vseh bolnicah s karcinomom endometrija se zato opravlja presejanje za sindrom Lynch, in sicer z imunohistokemičnim barvanjem za izražanje beljakovin popravljanja neujemanja in/ali z določanjem mikrosatelitne nestabilnosti iz primarnega tumorja. Pri vseh je tudi zelo pomembno natančno preveriti družinsko in osebno anamnezo drugih malignih ali benignih tumorjev. Na ta način aktivno iščemo tiste, ki imajo večjo verjetnost, da so nosilke genetskih okvar, povezanih z dedno obliko raka telesa maternice. Te potrebujejo napotitev in obravnavo pri kliničnem genetiku. V Ambulanti za onkološko genetsko svetovanje Onkološkega inštituta Ljubljana obravnava teh bolnic in njihovih svojcev poteka v okviru multidisciplinarne obravnave. Nosilci podedovanih genskih okvar lahko na podlagi genetskega izvida informirano soodločajo o preventivnih ukrepih glede na njihovo ogroženost za rake, ki so povezani v določen dedni sindrom.
Ključne besede: rak maternice, ginekološki raki, ginekološka onkologija
Objavljeno v DiRROS: 01.06.2023; Ogledov: 416; Prenosov: 179
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