BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer
Identifikátory výsledku
Kód výsledku v 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>
Výsledek na webu
<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>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer
Popis výsledku v původním jazyce
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.
Název v anglickém jazyce
BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer
Popis výsledku anglicky
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.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10603 - Genetics and heredity (medical genetics to be 3)
Návaznosti výsledku
Projekt
—
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2017
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Cancer research
ISSN
0008-5472
e-ISSN
—
Svazek periodika
77
Číslo periodika v rámci svazku
11
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
12
Strana od-do
2789-2799
Kód UT WoS článku
000402546200004
EID výsledku v databázi Scopus
2-s2.0-85020735683