Genome-wide Association Study Identifies 32 Novel Breast Cancer Susceptibility Loci From Overall and Subtype-Specific Analyses
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F20%3A00078404" target="_blank" >RIV/00209805:_____/20:00078404 - isvavai.cz</a>
Result on the web
<a href="https://pubmed.ncbi.nlm.nih.gov/32424353/?from_term=foretova+l&from_sort=date&from_pos=1" target="_blank" >https://pubmed.ncbi.nlm.nih.gov/32424353/?from_term=foretova+l&from_sort=date&from_pos=1</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41588-020-0609-2" target="_blank" >10.1038/s41588-020-0609-2</a>
Alternative languages
Result language
angličtina
Original language name
Genome-wide Association Study Identifies 32 Novel Breast Cancer Susceptibility Loci From Overall and Subtype-Specific Analyses
Original language description
Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 x 10-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.
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
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature genetics
ISSN
1061-4036
e-ISSN
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Volume of the periodical
52
Issue of the periodical within the volume
6
Country of publishing house
US - UNITED STATES
Number of pages
10
Pages from-to
572-581
UT code for WoS article
000533846800005
EID of the result in the Scopus database
2-s2.0-85085167024