Possible impact of HLA class I and class II on malignancies driven by a single germ‐line BRCA1 mutation

Ivanova, Milena; Ormandjieva, Anastasia; Dodova, R.; Kaneva, Radka; Shivarov, Velizar

doi:10.1111/iji.12631

Cited by 2 publications

(1 citation statement)

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“…Both cervical and oral cavity cancers are associated with HPV infection, which may explain the role of the HLA-DQB1*06:03P allele. In agreement with previous studies [35,36], we identi ed HLA-DQB1*06:03 as a protective allele also for breast and ovarian cancer, however, the mechanistic basis for its cancer risk-reducing role is unknown.…”

Section: Discussionsupporting

confidence: 91%

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

Kuligina,

Romanko,

Jankevic

et al. 2024

Preprint

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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 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 </= 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.

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Section: Discussionsupporting

confidence: 91%