| Title: |
HLA gene polymorphism is a modifier of age-related breast cancer penetrance in carriers of BRCA1 pathogenic alleles |
| Authors: |
Kuligina, Ekaterina S.; Romanko, Alexandr A.; Jankevic, Tatjana; Martianov, Aleksandr S.; Ivantsov, Alexandr O.; Sokolova, Tatyana N.; Trofimov, Dmitry; Kashyap, Aniruddh; Cybulski, Cezary; Lubiński, Jan; Imyanitov, Evgeny N. |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2024 |
| Description: |
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 (/= 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 towards 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 |
| Document Type: |
other/unknown material |
| Language: |
unknown |
| DOI: |
10.21203/rs.3.rs-3897419/v1 |
| Availability: |
http://dx.doi.org/10.21203/rs.3.rs-3897419/v1; https://www.researchsquare.com/article/rs-3897419/v1; https://www.researchsquare.com/article/rs-3897419/v1.html |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.CCD6B386 |
| Database: |
BASE |