Association of germline CHEK2 gene variants with risk and prognosis of non-Hodgkin lymphoma
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F75010330%3A_____%2F15%3A00010993" target="_blank" >RIV/75010330:_____/15:00010993 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/15:10312707 RIV/00064165:_____/15:10312707
Result on the web
<a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0140819" target="_blank" >http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0140819</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1371/journal.pone.0140819" target="_blank" >10.1371/journal.pone.0140819</a>
Alternative languages
Result language
angličtina
Original language name
Association of germline CHEK2 gene variants with risk and prognosis of non-Hodgkin lymphoma
Original language description
The checkpoint kinase 2 gene (CHEK2) codes for the CHK2 protein, an important mediator of the DNA damage response pathway. The CHEK2 gene has been recognized as a multi-cancer susceptibility gene; however, its role in non-Hodgkin lymphoma (NHL) remains unclear. We performed mutation analysis of the entire CHEK2 coding sequence in 340 NHL patients using denaturing high-performance liquid chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA). Identified hereditary variants were genotyped in 445 non-cancer controls. The influence of CHEK2 variants on disease risk was statistically evaluated. Identified CHEK2 germline variants included four truncating mutations (found in five patients and no control; P = 0.02) and nine missense variants (found in 21 patients and 12 controls; P = 0.02). Carriers of non-synonymous variants had an increased risk of NHL development [odds ratio (OR) 2.86; 95% confidence interval (CI) 1.42-5.79] and an unfavorable prognosis [hazard ratio (HR) of progression-free survival (PFS) 2.1; 95% CI 1.12-4.05]. In contrast, the most frequent intronic variant c.319+43dupA (identified in 22% of patients and 31% of controls) was associated with a decreased NHL risk (OR = 0.62; 95% CI 0.45-0.86), but its positive prognostic effect was limited to NHL patients with diffuse large B-cell lymphoma (DLBCL) treated by conventional chemotherapy without rituximab (HR-PFS 0.4; 94% CI 0.17-0.74). Our results show that germ-line CHEK2 mutations affecting protein coding sequence confer a moderately-increased risk of NHL, they are associated with an unfavorable NHL prognosis, and they may represent a valuable predictive biomarker for patients with DLBCL.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FD - Oncology and haematology
OECD FORD branch
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Result continuities
Project
<a href="/en/project/NT12193" target="_blank" >NT12193: Diffuse large B-cell and follicular lymphoma - the analysis of prognostic factors and therapeutic strategies on patient´s outcome; Lymphoma Project in the Czech Republic.</a><br>
Continuities
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Others
Publication year
2015
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
PLoS One
ISSN
1932-6203
e-ISSN
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Volume of the periodical
10
Issue of the periodical within the volume
10
Country of publishing house
US - UNITED STATES
Number of pages
15
Pages from-to
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UT code for WoS article
000363804200018
EID of the result in the Scopus database
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