Vpliv spremembe ocen parametrov znotraj Tyrer-Cuzickovega modela na izračun individualne ogroženosti z rakom dojk

BIRK, MOJCA (avtor), Zadnik, Vesna (mentor), Ružić Gorenjec, Nina (komentor)

Tyrer-Cuzickov model napoveduje tveganje za raka dojk v določenem časovnem obdobju, natančneje verjetnost, da posameznica zboli za rakom dojk do neke starosti, če do sedaj še ni zbolela. Model sloni na populacijski funkciji preživetja in funkcijah preživetja nosilcev mutacij genov BRCA1 in BRCA2. Segregacijski del modela upošteva starost posameznice in genetske dejavnike tveganja, ki jih pridobimo iz družinske anamneze raka dojk in jajčnikov ali genetskega testiranja. V regresijskem delu modela upoštevamo še ostale osebne dejavnike tveganja, kot so starost ob menarhi, rojstvo otrok, starost ob rojstvu prvega otroka, menopavzni status, prejemanje hormonske nadomestne terapije, gostota dojk idr. Avtorji Tyrer-Cuzickovega modela so v program IBIS Risk Evaluator v8 vključili tudi incidenco raka dojk v slovenski populaciji. V magistrskem delu nas je zanimalo, ali sprememba populacijske funkcije preživetja in sprememba funkcij preživetja nosilcev mutacij genov BRCA1 in BRCA2 prinese strokovno pomembne razlike v izračunu tveganja za raka dojk. Podrobno smo preučili članka o Tyrer-Cuzickovem modelu, v katerih marsikateri del modela ni natančno razložen. V programskem okolju R smo implementirali izračun tveganja za raka dojk in primerjali izračune tveganja po programu IBIS Risk Evaluator v6 z našimi izračuni. Implementacija modela nam je omogočila, da smo spremenili ocene parametrov znotraj modela, natančneje funkcije preživetja splošne populacije in nosilcev mutacij genov BRCA1 in BRCA2. Razlike v izračunu tveganja samo preučili na vzorcu 350 posameznic, ki so bile vključene v preventivno obravnavo v Centru za bolezni dojk in torej še niso zbolele za rakom dojk. Primerjali smo porazdelitev tveganj in porazdelitev posameznic v splošno, zmerno ter visoko kategorijo ogroženosti z rakom dojk. S pomočjo paketa Shiny smo v programskem okolju R ustvarili interaktivno spletno aplikacijo za izračun tveganja za raka dojk. Pokazali smo, da pri spremembi populacijske funkcije preživetja z britanske na slovensko pride do strokovno pomembnih razlik, medtem ko sprememba funkcij preživetja nosilcev mutacij genov BRCA1 in BRCA2 ne prinese strokovno pomembne razlike v porazdelitvi tveganj ali v porazdelitvi posameznic v kategorije ogroženosti. V spletno aplikacijo za izračun tveganja za raka dojk vnesemo osebne dejavnike tveganja za raka dojk in anamnezo raka dojk ter jajčnikov v družini. Aplikacija poda izračun osebnega in populacijskega desetletnega tveganja za raka dojk ter verjetnosti, da je oseba nosilka mutacije gena BRCA1 ali BRCA2. Podatke o posameznici in njenem tveganju za raka dojk shranimo v Excelovo datoteko, kar nam omogoča lažjo nadaljnjo analizo podatkov.

• Jezik: Slovenski jezik
• Ključne besede: Tyrer-Cuzickov model, gen BRCA1, gen BRCA2, tveganje, rak dojk
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FE - Fakulteta za elektrotehniko
• Leto izida: 2020
• PID: 20.500.12556/RUL-121900
• Datum objave v RUL: 06.11.2020

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Influence of changes in parameter estimates within the Tyrer-Cuzick model on the calculation of individual breast cancer risk

Izvleček

The Tyrer-Cuzick model predicts the risk of developing breast cancer in a certain age interval, i.e. the probability of developing breast cancer until a certain age if one has not yet developed breast cancer. The model is based on the population survival function and the survival functions of BRCA1 and BRCA2 gene mutation carriers. Segregation part of the model includes age and genetic risk factors obtained from the individual's family history of breast and ovarian cancer or results of genetic tests. The regression part of the model considers the other personal risk factors such as age at menarche, age at first childbirth, menopausal status, receiving hormone replacement therapy, breast density, etc. In the program IBIS Risk Evaluator v8, authors of Tyrer-Cuzick model included also the incidence of breast cancer in Slovenian population. In this master's thesis, we were interested whether changing population survival function and survival functions of BRCA1 and BRCA2 gene mutation carriers brings clinically significant differences in the calculated risk of developing breast cancer. We have studied two articles on the Tyrer-Cuzick model, where several parts of the model are not explained in detail. We implemented the model in R software environment and compared risk values according to the IBIS Risk Evaluator v6 program with our calculations. The implementation of the model gave us the ability to change the estimates of the parameters within the model, more precisely the population survival function and the survival functions of the BRCA1 and BRCA2 gene mutation carriers. Differences in risk calculation were examined on a sample of 350 individuals who were included in a preventive screening at the Breast Disease Center and had not yet been diagnosed with breast cancer at the time of screening. We compared the distributions of risk of developing breast cancer and the distribution of individuals into the general, moderate, and high risk category for breast cancer. With the use of the package Shiny, we created an interactive web application in the R software environment for calculating the risk of developing breast cancer. We showed that differences in risks are clinically significant if we change the population survival function from British to Slovenian, whereas the change in the survival functions of BRCA1 and BRCA2 gene mutation carriers did not lead to clinically significant differences in the distribution of risk or the distribution of individuals into risk categories. Our application for calculating the risk of developing breast cancer enables entering information about personal risk factors for breast cancer and family history of breast and ovarian cancer. The application returns an estimate of the risk of developing breast cancer in a 10 year period and the probability that the individual is a BRCA1 or BRCA2 gene mutation carrier. Data on the individual woman and her risk can be saved in an Excel file, which enables further data analysis.

• Ključne besede: Tyrer-Cuzick model, gene BRCA1, gene BRCA2, risk, breast cancer