Selected Genetic Polymorphisms Associated with Hypoxia and
Multidrug Resistance in Monoclonal Gammopathies Patients

J 2018

Selected Genetic Polymorphisms Associated with Hypoxia and Multidrug Resistance in Monoclonal Gammopathies Patients

ALMÁŠI, Martina, L. BESSE, Lucie BROŽOVÁ, Jiří JARKOVSKÝ, Renata BEZDĚKOVÁ et. al.

Basic information

Original name

Selected Genetic Polymorphisms Associated with Hypoxia and Multidrug Resistance in Monoclonal Gammopathies Patients

Name in Czech

Vybrané genetické polymorfizmy asociované s hypoxií a multilékovou rezistencí u pacientů s monoklonálními gamapatiemi

Authors

ALMÁŠI, Martina (203 Czech Republic), L. BESSE (756 Switzerland), Lucie BROŽOVÁ (203 Czech Republic, belonging to the institution), Jiří JARKOVSKÝ (203 Czech Republic, belonging to the institution), Renata BEZDĚKOVÁ (203 Czech Republic), Luděk POUR (203 Czech Republic, belonging to the institution), J. MINARIK (203 Czech Republic), P. KESSLER (203 Czech Republic), P. PAVLICEK (203 Czech Republic), L. ROZIAKOVA (703 Slovakia), Miroslav PENKA (203 Czech Republic), Roman HÁJEK (203 Czech Republic), Anna VAŠKŮ (203 Czech Republic, belonging to the institution) and Sabina ŠEVČÍKOVÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Klinická onkologie, Praha, Ambit Media, 2018, 0862-495X

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

Czech Republic

Confidentiality degree

není předmětem státního či obchodního tajemství

RIV identification code

RIV/00216224:14110/18:00103521

Organization unit

Faculty of Medicine

Keywords in English

multiple myeloma; hypoxia; genotype; polymorphism; qPCR

Abstract

V originále

Background: Adaptive response to hypoxia is regulated by several mechanisms and transcription factors, including hypoxia-inducible factors (HIFs). Activation of HIF-1alpha 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-1alpha and HIF-1beta 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-1beta (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-1alpha 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.

Citovat

ALMÁŠI, Martina, L. BESSE, Lucie BROŽOVÁ, Jiří JARKOVSKÝ, Renata BEZDĚKOVÁ, Luděk POUR, J. MINARIK, P. KESSLER, P. PAVLICEK, L. ROZIAKOVA, Miroslav PENKA, Roman HÁJEK, Anna VAŠKŮ and Sabina ŠEVČÍKOVÁ. Selected Genetic Polymorphisms Associated with Hypoxia and Multidrug Resistance in Monoclonal Gammopathies Patients. Klinická onkologie. Praha: Ambit Media, 2018, vol. 31, No 3, p. 213-229. ISSN 0862-495X.

@article{1430344,
   author = {Almáši, Martina and Besse, L. and Brožová, Lucie and Jarkovský, Jiří and Bezděková, Renata and Pour, Luděk and Minarik, J. and Kessler, P. and Pavlicek, P. and Roziakova, L. and Penka, Miroslav and Hájek, Roman and Vašků, Anna and Ševčíková, Sabina},
   article_location = {Praha},
   article_number = {3},
   keywords = {multiple myeloma; hypoxia; genotype; polymorphism; qPCR},
   language = {eng},
   issn = {0862-495X},
   journal = {Klinická onkologie},
   title = {Selected Genetic Polymorphisms Associated with Hypoxia and Multidrug Resistance in Monoclonal Gammopathies Patients},
   volume = {31},
   year = {2018}
}

TY  - JOUR
ID  - 1430344
AU  - Almáši, Martina - Besse, L. - Brožová, Lucie - Jarkovský, Jiří - Bezděková, Renata - Pour, Luděk - Minarik, J. - Kessler, P. - Pavlicek, P. - Roziakova, L. - Penka, Miroslav - Hájek, Roman - Vašků, Anna - Ševčíková, Sabina
PY  - 2018
TI  - Selected Genetic Polymorphisms Associated with Hypoxia and Multidrug Resistance in Monoclonal Gammopathies Patients
JF  - Klinická onkologie
VL  - 31
IS  - 3
SP  - 213-229
EP  - 213-229
PB  - Ambit Media
SN  - 0862495X
KW  - multiple myeloma
KW  - hypoxia
KW  - genotype
KW  - polymorphism
KW  - qPCR
N2  - Background: Adaptive response to hypoxia is regulated by several mechanisms and transcription factors, including hypoxia-inducible factors (HIFs). Activation of HIF-1alpha 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-1alpha and HIF-1beta 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-1beta (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-1alpha 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.
ER  -

ALMÁŠI, Martina, L. BESSE, Lucie BROŽOVÁ, Jiří JARKOVSKÝ, Renata BEZDĚKOVÁ, Luděk POUR, J. MINARIK, P. KESSLER, P. PAVLICEK, L. ROZIAKOVA, Miroslav PENKA, Roman HÁJEK, Anna VAŠKŮ and Sabina ŠEVČÍKOVÁ. Selected Genetic Polymorphisms Associated with Hypoxia and Multidrug Resistance in Monoclonal Gammopathies Patients. \textit{Klinická onkologie}. Praha: Ambit Media, 2018, vol.~31, No~3, p.~213-229. ISSN~0862-495X.

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