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

Oncotarget. 2016 Sep 13;7(37):59029-59048. doi: 10.18632/oncotarget.10665.

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.

Keywords: diabetes; genetic variants; multiple myeloma; survival.

Publication types

  • Meta-Analysis

MeSH terms

  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype*
  • Hepatocyte Nuclear Factor 1-beta / genetics*
  • Humans
  • Male
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / mortality
  • Polymorphism, Single Nucleotide
  • Sex Factors*
  • Survival Analysis
  • Zinc Transporter 8 / genetics*

Substances

  • HNF1B protein, human
  • SLC30A8 protein, human
  • Zinc Transporter 8
  • Hepatocyte Nuclear Factor 1-beta