A comprehensive analysis of germline predisposition to early-onset ovarian cancer
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F24%3A00079891" target="_blank" >RIV/00209805:_____/24:00079891 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/24:10482989 RIV/00216208:11310/24:10482989 RIV/00064211:_____/24:W0000004 RIV/00064165:_____/24:10482989
Result on the web
<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246516/" target="_blank" >https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246516/</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41598-024-66324-2" target="_blank" >10.1038/s41598-024-66324-2</a>
Alternative languages
Result language
angličtina
Original language name
A comprehensive analysis of germline predisposition to early-onset ovarian cancer
Original language description
The subset of ovarian cancer (OC) diagnosed LESS-THAN OR EQUAL TO 30yo represents a distinct subgroup exhibiting disparities from late-onset OC in many aspects, including indefinite germline cancer predisposition. We performed DNA/RNA-WES with HLA-typing, PRS assessment and survival analysis in 123 early-onset OC-patients compared to histology/stage-matched late-onset and unselected OC-patients, and population-matched controls. Only 6/123(4.9%) early-onset OC-patients carried a germline pathogenic variant (GPV) in high-penetrance OC-predisposition genes. Nevertheless, our comprehensive germline analysis of early-onset OC-patients revealed two divergent trajectories of potential germline susceptibility. Firstly, overrepresentation analysis highlighted a connection to breast cancer (BC) that was supported by the CHEK2 GPV enrichment in early-onset OC(p = 1.2 x 10(-4)), and the presumably BC-specific PRS(313), which successfully stratified early-onset OC-patients from controls(p = 0.03). The second avenue pointed towards the impaired immune response, indicated by LY75-CD302 GPV(p = 8.3 x 10(-4)) and diminished HLA diversity compared with controls(p = 3 x 10(-7)). Furthermore, we found a significantly higher overall GPV burden in early-onset OC-patients compared to controls(p = 3.8 x 10(-4)). The genetic predisposition to early-onset OC appears to be a heterogeneous and complex process that goes beyond the traditional Mendelian monogenic understanding of hereditary cancer predisposition, with a significant role of the immune system. We speculate that rather a cumulative overall GPV burden than specific GPV may potentially increase OC risk, concomitantly with reduced HLA diversity.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30204 - Oncology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Scientific reports
ISSN
2045-2322
e-ISSN
2045-2322
Volume of the periodical
14
Issue of the periodical within the volume
1
Country of publishing house
GB - UNITED KINGDOM
Number of pages
12
Pages from-to
16183
UT code for WoS article
001272466300041
EID of the result in the Scopus database
2-s2.0-85198400610