Selected genetic polymorphisms associated with hypoxia and multidrug resistance in monoclonal gammopathies patients

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F18%3A43917396" target="_blank" >RIV/00216208:11120/18:43917396 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14110/18:00103521 RIV/65269705:_____/18:00068731 RIV/00843989:_____/18:E0107147

Result on the web

<a href="https://doi.org/10.14735/amko2018213" target="_blank" >https://doi.org/10.14735/amko2018213</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.14735/amko2018213" target="_blank" >10.14735/amko2018213</a>

Result language

angličtina

Original language name

Selected genetic polymorphisms associated with hypoxia and multidrug resistance in monoclonal gammopathies patients

Original language description

Background: Adaptive response to hypoxia is regulated by several mechanisms and transcription factors, including hypoxia-inducible factors (HIFs). Activation of HIF-1α is associated with increased expression of P-glycoprotein and multidrug resistance in cancer cells. In this retrospective study, we analyzed candidate single-nucleotide polymorphisms (SNPs) in HIF-1α and HIF-1β associated with risk of monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma (MM). Patients and Methods: Genotypes of SNPs associated with hypoxia were determined in an independent cohort of monoclonal gammopathies (MG) (275 MM and 228 MGUS patients) and in 219 cancer-free controls by real time polymerase chain reaction allelic discrimination. Results: When MM patients were compared to controls, protective role of CG genotype compared to CC in HIF-1β (rs2228099) for MM development was observed (OR = 0.65; CI 0.45–0.95; p = 0.026). Even after adjustment for patients’ age and body mass index (BMI), there were significantly lower odds (OR = 0.55; p = 0.045) of developing MM patients of CG genotype in comparison to CC genotype. Log-rank test confirmed association of GT haplotype (rs11549467, rs2057482) in HIF-1α with better overall survival (median 41.8 months; (CI 35.1–48.5)) for “none GT” and median 93.8 months (CI 31.3–156.4) for “at least one GT” haplotype (p = 0.0500). Further, significant associations between SNPs in MDR1 and outcome of MM were found in 110 MM patients that underwent bortezomib-based treatment. Conclusion: Our study showed a genetic predisposition for risk of MG development and/or outcome of MM patients; nevertheless, further studies are needed to confirm our initial analysis.

Czech name

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Czech description

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Type

J_SC - Article in a specialist periodical, which is included in the SCOPUS database

CEP classification

—

OECD FORD branch

30205 - Hematology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Klinická onkologie

ISSN

0862-495X

e-ISSN

—

Volume of the periodical

31

Issue of the periodical within the volume

3

Country of publishing house

CZ - CZECH REPUBLIC

Number of pages

17

Pages from-to

213-229

UT code for WoS article

—

EID of the result in the Scopus database

2-s2.0-85055991021