Association Study of Selected Genetic Polymorphisms and Occurrence of Venous Thromboembolism in Patients With Multiple Myeloma Who Were Treated With Thalidomide

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Authors

ALMAŠI Martina ŠEVČÍKOVÁ Sabina SLABÝ Ondřej MÁJKOVÁ Petra MAISNAR Vladimír PENKA Miroslav PIKA Tomáš POUR Luděk RADOCHA Jakub ŠČUDLA Vlastimil ŠVÁCHOVÁ Hana HÁJEK Roman

Year of publication 2011
Type Article in Periodical
Magazine / Source Clinical Lymphoma, Myeloma & Leukemia
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.1016/j.clml.2011.03.024
Field Oncology and hematology
Keywords Allelic discrimination; Classification tree; Genotype; Real-time polymerase chain reaction; Single nucleotide polymorphisms
Description Venous thromboembolism (VTE), with the subsequent risk of pulmonary embolism, is a common adverse effect of thalidomide treatment in patients with multiple myeloma (MM). In our retrospective study, we analyzed candidate single-nucleotide polymorphisms (SNP), CINP (rs7011), CETP (rs289747), ALDH1A1 (rs610529), CDKN1A (rs3829963), GAN (rs2608555), vascular endothelial growth factor (rs699947), and ALDH1A1 (rs168351), previously identified in a large association study based on the hypothesis-driven candidate gene approach nominated by the International Myeloma Foundation "Bank On A Cure" (3404 SNPs). In that study, the researchers built a classification tree that enables prediction of individual risk of VTE in patients with MM. Genotypes of these SNPs were determined in an independent cohort of 111 patients with MM through TaqMan real-time polymerase chain reaction (PCR) allelic discrimination and were used for prediction of individual VTE risk. The results of this study did not confirm the ability of this classification tree to predict VTE risk in patients with MM from the Czech Republic; of these patients, 21 (19%) developed high-grade VTE. However, in patients with VTE, we found higher frequency of the AC genotype in the CDKN1A gene (42.9% vs. 16.7%; odds ratio 3.64) in comparison with the CC genotype. SNPs of other genes as well as age and sex of the patients had no statistically significant influence on the risk of VTE. Further studies are needed to confirm the initial analysis that provided predictive information of genetic variations in patients with myeloma that may influence risk of VTE.
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