Predsimptomatsko genetsko testiranje za dedni sindrom raka dojk in/ali jajčnikov The uptake of presymptomatic genetic testing for hereditary breast and/or ovarian cancer syndrome

Abstract

Izhodišče: Kaskadno testiranje je testiranje svojcev prvega dokazanega nosilca patogene različice/verjetno patogene različice (PR/VPR) določenega gena v družini. Uspešnost preventive rakavih bolezni v družini, v kateri je ugotovljena PR/VPR, je odvisna od identifikacije tistih krvnih sorodnikov, ki so prav tako nosilci družinske genetske okvare, pa sami še niso zboleli. Število krvnih sorodnikov iz družin z dednim sindromom za raka dojk in/ali jajčnikov (HBOC), ki se v sklopu obravnave na Onkološkem inštitutu Ljubljana (OIL) odločijo za predsimptomatsko svetovanje in testiranje po novoodkriti PR/VPR v družini, je trenutno neznano.
Namen: Namen raziskave je bil ugotoviti število krvnih sorodnikov, ki so se odločili za predsimptomatsko testiranje, ko je bila v družini dokazana PR/VPR v genu BRCA1 in/ali BRCA2, in analizirati njihove značilnosti.
Metode: Analizirali smo podatke, ki smo jih pridobili iz podatkovne zbirke Oddelka za onkološko klinično genetiko OIL med letoma 1999 in 2020, o testiranih in njihovih družinskih članih. Uporabili smo deskriptivne statistične metode.
Rezultati: Med 5158 napotenimi družinami s sumom na HBOC smo odkrili 785 BRCA1 in BRCA2 pozitivnih, kar pomeni 15,2 %. Od vseh 785 pozitivnih družin se pri 27 % (212/785) družin za genetsko svetovanje še ni odločil nihče od svojcev. V družinah, kjer so se svojci odločili za posvet (573 družin), se jih je 79 % oglasilo v prvih 12 mesecih od razkritja pozitivnega rezultata prvemu testiranemu. V teh 573 družinah se je skupno 1731 oseb odločilo za predsimptomatsko testiranje, od tega je bilo 80,3 % žensk. Povprečno število krvnih sorodnikov, ki so se med letoma 1999 in 2020 odločili za predsimptomatsko svetovanje in testiranje, je dva (2,21) na družino. Če odštejemo družine, v katerih se ni javil nihče od svojcev, pa so se javili povprečno trije (3,02) svojci na družino, torej so poleg nosilca družine na posvet prišli vsaj še trije.
Zaključek: Kaskadno testiranje je uspešen način ugotavljanja nosilcev PR/VPR v družini in v populaciji. Trenutno je edini dokazano uspešen način, s katerim lahko zdravim, bolj ogroženim posameznikom omogočimo preventivne ukrepe preprečevanja in zgodnjega odkrivanja raka, s čimer dokazano podaljšujemo življenja. Možnost za odločitev o preventivnih ukrepih bi morali tako imeti vsi krvni sorodniki ob pozitivnem rezultatu prvega testiranega. Treba bo raziskati, zakaj se pri slabi tretjini pozitivnih družin ni javil noben družinski član in kako lahko še izboljšamo klinične poti, da bi povečali odziv svojcev.

Abstract (Eng)

Background: Cascade testing is the testing of relatives of the first proven carrier of a pathogenic variant / probable pathogenic variant (PR / VPR) of a particular gene in a family. The success of cancer prevention in a particular family where a PR / VPR is detected depends on the identification of those blood relatives, who are also carriers of the familial variant but have not yet developed cancer. The number of blood relatives from families with hereditary breast and / or ovarian cancer syndrome (HBOC), who decide to undergo presymptomatic counselling and testing for a newly discovered PR / VPR in their family at the Institute of Oncology Ljubljana (OIL), is currently unknown.
Aim: The aim of the study was to determine the number of blood relatives who opted for presymptomatic testing when a PR / VPR was detected in BRCA1 and / or BRCA2 genes in the family and to analyse their characteristics.
Methods: We analysed data on patients and their family members obtained from the database of the Cancer Genetics Clinic at the OIL, who underwent testing between 1999 and 2020. We used descriptive statistical methods.
Results: Among 5158 referred families tested for HBOC, 785 carriers of BRCA1 and BRCA2 were detected, representing 15.2%. In 27% of 785 positive families (212/785) no family members opted for cascade testing to date. In the families where relatives decided to consult our cancer genetics clinic (573 families), 79% of them came within the first twelve months from the disclosure of a positive result to the index case. In these 573 families, a total of 1731 people opted for presymptomatic testing, of which 80.3% were women. The average number of blood relatives, who opted for presymptomatic counseling and testing between 1999 and 2020 is 2.21 per family (index case excluded). If we exclude families in which none of the relatives came for an assessment, an average of 3.02 relatives per family opted for cascade testing.
Conclusion: Cascade testing is a good way to identify PR / VPR carriers in the family and in the population. At present, it is practically the only way to identify healthy at-risk individuals and offer them prevention and early detection of cancer, which have been proven to prolong lives. Thus, all blood relatives should be able to choose preventive measures when there is a proven cancer predisposition in the family. In the future, we have to investigate why almost one third of positive families opt out of cascade testing and how we may further improve clinical pathways to increase the genetic testing/counselling uptake.