Type 2 diabetes-related variantsinfluence the risk of developing multiple myeloma: Results from the IMMEnSE consortium

Rafael Ríos, Carmen Belén Lupiañez, Daniele Campa, Alessandro Martino, Joaquin Martínez-López, Manuel Martínez-Bueno, Judit Varkonyi, Ramón García-Sanz, Krzysztof Jamroziak, Charles Dumontet, Andrés Jerez Cayuela, Marzena Wętek, Stephano Landi, Anna Maria Rossi, Fabienne Lesueur, Rui Manuel Reis, Victor Moreno, Herlander Marques, Artur Jurczyszyn, Vibeke AndersenUlla Vogel, Gabriele Buda, Enrico Orciuolo, Svend E.H. Jacobsen, Mario Petrini, Annette J. Vangsted, Federica Gemignani, Federico Canzian, Manuel Jurado, Juan Sainz

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Abstract

Type 2 diabetes (T2D) has been suggested to be a risk factor for multiple myeloma (MM), but the relationship between the two traits is still not well understood. The aims of this study were to evaluate whether 58 genome-wide-association-studies (GWAS)-identified common variants for T2D influence the risk of developing MM and to determine whether predictive models built with these variants might help to predict the disease risk. We conducted a case-control study including 1420MMpatients and 1858 controls ascertained through the International Multiple Myeloma (IMMEnSE) consortium. Subjects carrying the KCNQ1rs2237892T allele or the CDKN2A-2Brs2383208G/G, IGF1rs35767T/T and MADDrs7944584T/T genotypes had a significantly increased risk of MM(odds ratio (OR)=1.32-2.13) whereas those carrying the KCNJ11rs5215C, KCNJ11rs5219T and THADArs7578597C alleles or the FTOrs8050136A/A and LTArs1041981C/C genotypes showed a significantly decreased risk of developing the disease (OR=0.76-0.85). Interestingly, a prediction model including those T2D-related variants associated with the risk of MM showed a significantly improved discriminatory ability to predict the disease when compared to a model without genetic information (area under the curve (AUC)=0.645 vs AUC=0.629; P=4.05× 10-06). A gender-stratified analysis also revealed a significant gender effect modification for ADAM30rs2641348 and NOTCH2rs10923931 variants (Pinteraction=0.001 and 0.0004, respectively). Men carrying the ADAM30rs2641348C and NOTCH2rs10923931T alleles had a significantly decreased risk of MM whereas an opposite but not significant effect was observed in women (ORM=0.71 and ORM=0.66 vs ORW=1.22 and ORW=1.15, respectively). These results suggest that TD2-related variants may influence the risk of developing MM and their genotyping might help to improve MM risk prediction models.

Original languageEnglish
Pages (from-to)545-559
Number of pages15
JournalEndocrine-Related Cancer
Volume22
Issue number4
DOIs
Publication statusPublished - aug. 1 2015

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

Cite this

Ríos, R., Lupiañez, C. B., Campa, D., Martino, A., Martínez-López, J., Martínez-Bueno, M., Varkonyi, J., García-Sanz, R., Jamroziak, K., Dumontet, C., Cayuela, A. J., Wętek, M., Landi, S., Rossi, A. M., Lesueur, F., Reis, R. M., Moreno, V., Marques, H., Jurczyszyn, A., ... Sainz, J. (2015). Type 2 diabetes-related variantsinfluence the risk of developing multiple myeloma: Results from the IMMEnSE consortium. Endocrine-Related Cancer, 22(4), 545-559. https://doi.org/10.1530/ERC-15-0029