Dataset Information

A common variant within the HNF1B gene is associated with overall survival of multiple myeloma patients: results from the IMMEnSE consortium and meta-analysis.

ABSTRACT: Diabetogenic single nucleotide polymorphisms (SNPs) have recently been associated with multiple myeloma (MM) risk but their impact on overall survival (OS) of MM patients has not been analysed yet. In order to investigate the impact of 58 GWAS-identified variants for type 2 diabetes (T2D) on OS of patients with MM, we analysed genotyping data of 936 MM patients collected by the International Multiple Myeloma rESEarch (IMMENSE) consortium and an independent set of 700 MM patients recruited by the University Clinic of Heidelberg. A meta-analysis of the cox regression results of the two sets showed that rs7501939 located in the HNF1B gene negatively impacted OS (HRRec= 1.44, 95% CI = 1.18-1.76, P = 0.0001). The meta-analysis also showed a noteworthy gender-specific association of the SLC30A8rs13266634 SNP with OS. The presence of each additional copy of the minor allele at rs13266634 was associated with poor OS in men whereas no association was seen in women (HRMen-Add = 1.32, 95% CI 1.13-1.54, P = 0.0003). In conclusion, these data suggest that the HNF1Brs7501939 SNP confers poor OS in patients with MM and that a SNP in SLC30A8 affect OS in men.

SUBMITTER: Rios-Tamayo R

PROVIDER: S-EPMC5312293 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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A common variant within the HNF1B gene is associated with overall survival of multiple myeloma patients: results from the IMMEnSE consortium and meta-analysis.

Ríos-Tamayo Rafael R Lupiañez Carmen Belén CB Campa Daniele D Hielscher Thomas T Weinhold Niels N Martínez-López Joaquin J Jerez Andrés A Landi Stefano S Jamroziak Krzysztof K Dumontet Charles C Wątek Marzena M Lesueur Fabienne F Reis Rui Manuel RM Marques Herlander H Jurczyszyn Artur A Vogel Ulla U Buda Gabriele G García-Sanz Ramón R Orciuolo Enrico E Petrini Mario M Vangsted Annette J AJ Gemignani Federica F Försti Asta A Goldschmidt Hartmut H Hemminki Kari K Canzian Federico F Jurado Manuel M Sainz Juan J

Oncotarget 20160901 37

Diabetogenic single nucleotide polymorphisms (SNPs) have recently been associated with multiple myeloma (MM) risk but their impact on overall survival (OS) of MM patients has not been analysed yet. In order to investigate the impact of 58 GWAS-identified variants for type 2 diabetes (T2D) on OS of patients with MM, we analysed genotyping data of 936 MM patients collected by the International Multiple Myeloma rESEarch (IMMENSE) consortium and an independent set of 700 MM patients recruited by the ...[more]

PMID: 27437873

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Project description:Previous results from an interim analysis of an open-label, randomized, phase 3 study demonstrated that bortezomib combined with pegylated liposomal doxorubicin (PLD) was superior to bortezomib monotherapy in patients with relapsed/refractory multiple myeloma who had previously received one or more lines of therapy. Protocol-defined final survival data from that study are provided here.Patients were randomized (1:1) to receive either bortezomib alone (1.3 mg/m(2) intravenously on days 1, 4, 8, and 11 of every 21-day cycle) or bortezomib-PLD (bortezomib plus PLD 30 mg/m(2) intravenously on day 4). The primary endpoint was the time to progression. Secondary efficacy endpoints included overall survival (OS), progression-free survival, and the overall response rate.In total, 646 patients (bortezomib-PLD, n = 324; bortezomib alone, n = 322) were randomized between December, 2004, and March, 2006. On the clinical cutoff date (May 16, 2014) for the final survival analysis, at a median follow-up of 103 months, 79% of patients had died (bortezomib-PLD group: 253 of 324 patients; 78%; bortezomib alone group: 257 of 322 patients; 80%). The median OS in the bortezomib-PLD group was 33 months (95% confidence interval [CI], 28.9-37.1) versus 30.8 months (95% CI, 25.2-36.5) in the bortezomib alone group (hazard ratio, 1.047; 95% CI, 0.879-1.246; P = .6068). Salvage therapies included conventional and novel drugs, which were well balanced between the two treatment groups.Despite inducing a superior time to progression, long-term follow-up revealed that PLD-bortezomib did not improve OS compared with bortezomib alone in patients with relapsed/refractory multiple myeloma. The inability to sustain the early observed survival advantage may have been caused by the effects of subsequent lines of therapy, and underscores the need for long-term follow-up of phase 3 trials while recognizing the challenge of having adequate power to detect long-term differences in OS. Cancer 2016;122:2050-6. © 2016 American Cancer Society.

Dataset Information

A common variant within the HNF1B gene is associated with overall survival of multiple myeloma patients: results from the IMMEnSE consortium and meta-analysis.

Publications

A common variant within the HNF1B gene is associated with overall survival of multiple myeloma patients: results from the IMMEnSE consortium and meta-analysis.

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