HLA gene polymorphism is a modifier of age-related breast cancer penetrance in carriers of BRCA1 pathogenic alleles.

Autor: Kuligina ES; N.N. Petrov Institute of Oncology, St. Petersburg, Russia. kate.kuligina@gmail.com.; Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Pesochny-2, St. Petersburg, Russia, 197758. kate.kuligina@gmail.com., Romanko AA; N.N. Petrov Institute of Oncology, St. Petersburg, Russia.; St. Petersburg Pediatric Medical University, St. Petersburg, Russia., Jankevic T; DNA-Technology LLC, Moscow, Russia., Martianov AS; N.N. Petrov Institute of Oncology, St. Petersburg, Russia., Ivantsov AO; N.N. Petrov Institute of Oncology, St. Petersburg, Russia., Sokolova TN; N.N. Petrov Institute of Oncology, St. Petersburg, Russia., Trofimov D; DNA-Technology LLC, Moscow, Russia., Kashyap A; International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, Szczecin, Poland., Cybulski C; International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, Szczecin, Poland., Lubiński J; International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, Szczecin, Poland., Imyanitov EN; N.N. Petrov Institute of Oncology, St. Petersburg, Russia.; St. Petersburg Pediatric Medical University, St. Petersburg, Russia.; Mechnikov North-Western Medical University, St. Petersburg, Russia.
Jazyk: angličtina
Zdroj: Breast cancer research and treatment [Breast Cancer Res Treat] 2024 Sep 21. Date of Electronic Publication: 2024 Sep 21.
DOI: 10.1007/s10549-024-07497-2
Abstrakt: Purpose: Female carriers of germline BRCA1 mutations almost invariably develop breast cancer (BC); however, the age at onset is a subject of variation. We hypothesized that the age-related penetrance of BRCA1 mutations may depend on inherited variability in the host immune system.
Methods: Next-generation sequencing was utilized for genotyping of HLA class I/II genes (HLA-A, HLA-B, HLA-C, HLA-DPB1, HLA-DQB1, and HLA-DRB1/3/4/5) in patients with BRCA1-associated BC with early (< / = 38 years, n = 215) and late (> / = 58 years, n = 108) age at onset.
Results: HLA-DQB1*06:03P prevalence was higher in the late-onset group due to the excess of allele carriers [25/108 (23.1%) vs. 22/215 (10.2%); OR 2.96, p < 0.001]. For all HLA-I loci, there was a trend toward an increase in the number of homozygotes in the early-onset group. This trend reached statistical significance for the HLA-A [14.4% vs. 6.5%, p = 0.037; OR 2.4, p = 0.042]. The frequencies of HLA-DPB1, HLA-DQB1, and HLA-DRB1/3/4/5 homozygous genotypes did not differ between young-onset and late-onset patients. The maximum degree of homozygosity detected in this study was 6 out of 7 HLA class I/II loci; all six carriers of these genotypes were diagnosed with BC at the age < / = 38 years [OR 6.97, p = 0.187].
Conclusion: HLA polymorphism may play a role in modifying the penetrance of BRCA1 pathogenic variants. Certain HLA alleles or HLA homozygosity may modify the risk of BC in BRCA1 carriers.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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