Author(s):
Ríos, Rafael ; Lupiañez, Carmen Belén ; Campa, Daniele ; Martino, Alessandro ; Martínez-López, Joaquin ; Martínez-Bueno, Manuel ; Varkonyi, Judit ; García-Sanz, Ramón ; Jamroziak, Krzysztof ; Dumontet, Charles ; Jerez Cayuela, Andrés ; Wetek, Marzena ; Landi, Stefano ; Rossi, Anna Maria ; Lesueur, Fabienne ; Reis, R. M. ; Moreno, Victor ; Marques, Herlander ; Jurczyszyn, Artur ; Andersen, Vibeke ; Vogel, Ulla ; Buda, Gabriele ; Orciuolo, Enrico ; Jacobsen, Svend E. H. ; Petrini, Mario ; Vangsted, Annette Juul ; Gemignani, Federica ; Canzian, Federico ; Jurado, Manuel ; Sainz, Juan
Date: 2015
Persistent ID: https://hdl.handle.net/1822/40536
Origin: RepositóriUM - Universidade do Minho
Subject(s): multiple myeloma; diabetes; genetic variants; susceptibility
Description
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 1420 MM patients 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.
