BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F17%3A00077920" target="_blank" >RIV/00209805:_____/17:00077920 - isvavai.cz</a>
Result on the web
<a href="http://cancerres.aacrjournals.org/content/77/11/2789.long" target="_blank" >http://cancerres.aacrjournals.org/content/77/11/2789.long</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1158/0008-5472.CAN-16-2568" target="_blank" >10.1158/0008-5472.CAN-16-2568</a>
Alternative languages
Result language
angličtina
Original language name
BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer
Original language description
Breast cancer risks conferred by many germline missense variants in the BRCA1 and BRCA2 genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case-control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.9104A>C, p.Tyr3035Ser (OR 1/4 2.52; P 1/4 0.04), and BRCA1 c.5096G>A, p.Arg1699Gln (OR 1/4 4.29; P 1/4 0.009) variant were associated with moderately increased risks of breast cancer among Europeans, whereas BRCA2 c.7522G>A, p.Gly2508Ser (OR 1/4 2.68; P 1/4 0.004), and c.8187G>T, p.Lys2729Asn (OR 1/4 1.4; P 1/4 0.004) were associated with moderate and low risks of breast cancer among Asians. Functional characterization of the BRCA2 variants using four quantitative assays showed reduced BRCA2 activity for p.Tyr3035Ser compared with wild-type. Overall, our results show how BRCA2 missense variants that influence protein function can confer clinically relevant, moderately increased risks of breast cancer, with potential implications for risk management guidelines in women with these specific variants.
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
10603 - Genetics and heredity (medical genetics to be 3)
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cancer research
ISSN
0008-5472
e-ISSN
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Volume of the periodical
77
Issue of the periodical within the volume
11
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
2789-2799
UT code for WoS article
000402546200004
EID of the result in the Scopus database
2-s2.0-85020735683