PhD Scientific Days 2026

Poster Session 2.E - Pathological and Oncological Sciences

HLA Polymorphisms Effect Cancer Penetrance in Women Who Carry Germline Pathogenic BRCA1 Variants

Előadó neve

Mr. Kákonyi, Marcell

Neptune code

Z56X0W

Előadó munkahelye

National Institute of Oncology

Előadó telefonszáma

+36205853122

Előadó e-mail címe

kakonyi.marcell@stud.semmelweis.hu

Az előadás címe

HLA Polymorphisms Effect Cancer Penetrance in Women Who Carry Germline Pathogenic BRCA1 Variants

Szerző(k) neve és munkahelye

Marcell Kákonyi¹, Barna Budai², Anikó Bozsik², Tímea Pócza², János Papp², István Likó², Henriett Butz², Attila Patócs², Vince Kornél Grolmusz²

1: National Institute of Oncology
2: Department of Molecular Genetics, National Institute of Oncology

Bemutatás módja

Poszter

Szekció

Poster Session 2.E - Pathological and Oncological Sciences

Language of the presentation

English

Preferred session

Pathological and Oncological Sciences

Összefoglaló szövege

Introduction
Germline pathogenic variants in BRCA1 (gpath(BRCA1)) confer a cumulative risk of 72% for breast cancer (BrC) and 44% for ovarian cancer (OC) by age 80. BrC and OC risk fluctuate based on the degree of family history, implying that genetic modifiers influence penetrance, and emerging evidence suggests that immune-mediated mechanisms also play a role in carcinogenesis. Studies indicate that variation within the human leukocyte antigen (HLA) region may play a role in determining cancer susceptibility.
Aims
We aimed to analyse HLA polymorphisms on the age-related cancer penetrance of OC and BrC in women living with gpath(BRCA1).
Methods
590 women with gpath(BRCA1) were enrolled in the study. Genetic counseling and diagnostic procedures were conducted at the Dept. of Molecular Genetics, National Institute of Oncology. HLA typing was conducted via next-generation sequencing using the Protrans N5-LR11 kit and Illumina NextSeq instrument. Allele assignment was carried out via the HLA-HD software. Statistical analysis was conducted in a time-to-event survival analysis framework, where follow-up was defined from birth to first cancer diagnosis or censoring at risk-reducing surgery, lost to follow-up or death. The effect of all HLA alleles was assessed by Cox-regression and log-rank tests.
Results
Out of the 590 participants 353 (59.8%) individuals were diagnosed with BrC and 128 (21.7%) with OC; 35 (5.93%) women had both diagnoses, and 144 (24.4%) remained cancer-free during the follow-up. On 2-field resolution 243 distinct HLA alleles were identified across 11 loci.
No significant associations were seen between BrC and HLA polymorphisms. The presence the HLA-DQ6.2 haplotype - containing DQB1*06:02, DQB1*02:01 and DRB1*15:01 - was associated with an unfavorable age-related penetrance of OC (p=0.0096, HR=2.43).
Conclusion
HLA polymorphisms appear to modulate ovarian cancer penetrance and age at onset in gpath(BRCA1) carriers, with the strongest association identified for the HLA-DQ6.2 haplotype.

Funding
National Tumor Biology Laboratory (2022-2.1.1-NL-2022-00010)
Hungarian Thematic Excellence Prog. (TKP2021-EGA-44)
Lendület-Momentum, Hungarian Academy of Sciences (LP2025-21/2025)
National Research, Development and Innovation Office (NKFIH-FK-138377)

Email: kakonyi.marcell@stud.semmelweis.hu
Univ: Semmelweis Univ.
Superv.: Vince Kornél Grolmusz

University

Semmelweis University

Supervisor

Vince Kornél Grolmusz

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

phd.section.field

before finishing undergraduate studies (TDK, MD-PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

9754

Start

18:54

End

18:57