TITLE

Polymorphisms in the multiple drug resistance protein 1 and in P-glycoprotein 1 are associated with time to event outcomes in patients with advanced multiple myeloma treated with bortezomib and pegylated liposomal doxorubicin

AUTHOR(S)
Buda, Gabriele; Ricci, Deborah; Huang, C. Chris; Favis, Reyna; Cohen, Nadine; Zhuang, Sen H.; Harousseau, Jean-Luc; Sonneveld, Pieter; Bladé, Joan; Orlowski, Robert Z.
PUB. DATE
November 2010
SOURCE
Annals of Hematology;Nov2010, Vol. 89 Issue 11, p1133
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Single nucleotide polymorphisms (SNPs) in the multiple drug resistance protein 1 (MRP1) and P-glycoprotein 1 (MDR1) genes modulate their ability to mediate drug resistance. We therefore sought to retrospectively evaluate their influence on outcomes in relapsed and/or refractory myeloma patients treated with bortezomib or bortezomib with pegylated liposomal doxorubicin (PLD). The MRP1/R723Q polymorphism was found in five subjects among the 279 patient study population, all of whom received PLD + bortezomib. Its presence was associated with a longer time to progression (TTP; median 330 vs. 129 days; p = 0.0008), progression-free survival (PFS; median 338 vs. 129 days; p = 0.0006), and overall survival ( p = 0.0045). MDR1/3435(C > T), which was in Hardy-Weinberg equilibrium, showed a trend of association with PFS ( p = 0.0578), response rate ( p = 0.0782) and TTP ( p = 0.0923) in PLD + bortezomib patients, though no correlation was found in the bortezomib arm. In a recessive genetic model, MDR1/3435 T was significantly associated with a better TTP ( p = 0.0405) and PFS ( p = 0.0186) in PLD + bortezomib patients. These findings suggest a potential role for MRP1 and MDR1 SNPs in modulating the long-term outcome of relapsed and/or refractory myeloma patients treated with PLD + bortezomib. Moreover, they support prospective studies to determine if such data could be used to tailor therapy to the genetic makeup of individual patients.
ACCESSION #
53704494

 

Related Articles

  • Multiallelic models of genetic effects and variance decomposition in non-equilibrium populations. Álvarez-Castro, José; Yang, Rong-Cai // Genetica;Sep2011, Vol. 139 Issue 9, p1119 

    Quantitative genetics stems from the theoretical models of genetic effects, which are re-parameterizations of the genotypic values into parameters of biological (genetic) relevance. Different formulations of genetic effects are adequate to address different subjects. We thus need to generalize...

  • Short Tandem Repeat Polymorphism in the Flanking Region of the Human Phosphoglycerate Kinase Gene in a Japanese Population. Jian Tie; Serizawa, Yuka; Oshida, Shigemi; Usami, Ron; Yoshida, Yasuhiko // Human Biology;Apr2006, Vol. 78 Issue 2, p243 

    Abstract The human phosphoglycerate kinase (PGKI) gene is located within Xq11-Xq13 and is closely linked to the androgen receptor gene within a region implicated in a number of X-chromosome-linked urologic disorders. A polymorphism of a TATC short tandem repeat (STR) is present downstream from...

  • Reply from the Authors. Kocsis, István; Györffy, Balázs; Vásárhelyi, Barna // Kidney International;Oct2004, Vol. 66 Issue 4, p1711 

    Replies to a letter to the editor about the authors' article on the underuse of Hardy-Weinberg equilibrium calculations in the study of genetic polymorphisms.

  • Underuse of Hardy-Weinberg equilibrium. Sunder-Plassmann, Gere; Födinger, Manuela // Kidney International;Oct2004, Vol. 66 Issue 4, p1711 

    Presents a letter to the editor about the underuse of the Hardy-Weinberg equilibrium in the study of genetic polymorphism.

  • Associations between serotonin transporter gene polymorphisms and heat pain perception in adults with chronic pain. Hooten, W. Michael; Hartman, William R.; Black III, John Logan; Laures, Heidi J.; Walker, Denise L. // BMC Medical Genetics;2013, Vol. 14 Issue 1, p1 

    Background: The triallelic serotonin transporter gene linked polymorphic region (5-HTTLPR) has been associated with alterations in thermal pain perception. The primary aim of this study was to investigate the associations between heat pain (HP) perception and the triallelic 5-HTTLPR in a large...

  • A Primary Assembly of a Bovine Haplotype Block Map Based on a 15,036-Single-Nucleotide Polymorphism Panel Genotyped in Hoistein-Friesian Cattle. Khatkar, Mehar S.; Zenger, Kyall R.; Hobbs, Matthew; Hawken, Rachel J.; Cavanagh, Julie A. L.; Barris, Wes; McClintock, Alexander E.; McClintock, Sara; Thomson, Peter C.; Tier, Bruce; Nicholas, Frank W.; Raadsma, Herman W. // Genetics;Jun2007, Vol. 176 Issue 2, p763 

    Analysis of data on 1000 Holstein-Friesian bulls genotyped for 15,036 single-nucleotide polymorphisms (SNPs) has enabled genomewide identification of haplotype blocks and tag SNPs. A final subset of 9195 SNPs in Hardy-Weinberg equilibrium and mapped on autosomes on the bovine sequence assembly...

  • Lack of Association Between Vitamin D Receptor Genotypes and Haplotypes With Fat-Free Mass Postmenopausal Brazilian Women. Lima, Ricardo Moreno; De Abreu, Breno Silva; Gentil, Paulo; Lins, Tulio Cesar De Lima; Grattapaglia, Dário; Pereira, Rinaldo Wellerson; De Oliveira, Ricardo Jacó // Journals of Gerontology Series A: Biological Sciences & Medical ;Sep2007, Vol. 62 Issue 9, p966 

    The relationship between vitamin D receptor (VDR) ApaI, CDX2, BsmI, FokI, and TaqI polymorphisms and fat-free mass (FFM) were examined in 191 postmenopausal Brazilian women (mean age 67.87 ± 5.22 years). Participants underwent FFM measurements by dual-energy x-ray absorptiometry (DEXA)....

  • Development of two multiplex PCR systems for the analysis of 14 X-chromosomal STR loci in a southern Brazilian population sample. Penna, Larissa; Silva, Fernanda; Salim, Patricia; Ewald, Gisele; Jobim, Mariana; Magalhães, José; Jobim, Luiz // International Journal of Legal Medicine;Mar2012, Vol. 126 Issue 2, p327 

    We developed two multiplex systems for the coamplification of X-chromosomal short tandem repeats (STRs). X-Multiplex 1 consisted of DXS6807, DXS6800, DXS7424, DXS101, GATA172D05 and HPRTB and X-Multiplex 2 consisted of DXS8378, DXS9898, DXS6801, DXS6809, DXS6789, DXS7133, DXS8377 and DXS7423. In...

  • Development and Characterization of EST-SSR Markers from Scapharca broughtonii and Their Transferability in Scapharca subcrenata and Tegillarca granosa. Meng Li; Ling Zhu; Chun-Ya Zhou; Lin Lin; Yan-Jun Fan; Zhi-Meng Zhuang // Molecules;Sep2012, Vol. 17 Issue 9, p10716 

    Twenty-five novel EST-derived simple sequence repeat (EST-SSR) markers were developed in the ark shell Scapharca broughtonii. Polymorphisms of these EST-SSR markers were evaluated in 48 wild individuals collected from Shidao, Shandong Province, China. A total of 202 alleles were detected at 25...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics