Type 2 diabetes-related variants influence 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 Andersen & 10 andre Ulla Vogel, Gabriele Buda, Enrico Orciuolo, Svend E H Jacobsen, Mario Petrini, Annette J Vangsted, Federica Gemignani, Federico Canzian, Manuel Jurado, Juan Sainz

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftEndocrine - Related Cancer
Vol/bind22
Udgave nummer4
Sider (fra-til)545-59
Antal sider15
ISSN1351-0088
DOI
StatusUdgivet - aug. 2015

Fingeraftryk

Type 2 Diabetes Mellitus
Alleles
Area Under Curve
Odds Ratio
Genome-Wide Association Study
Genetic Models
Case-Control Studies

Citer dette

Ríos, R., Lupiañez, C. B., Campa, D., Martino, A., Martínez-López, J., Martínez-Bueno, M., ... Sainz, J. (2015). Type 2 diabetes-related variants influence the risk of developing multiple myeloma: results from the IMMEnSE consortium. Endocrine - Related Cancer, 22(4), 545-59. https://doi.org/10.1530/ERC-15-0029
Ríos, Rafael ; Lupiañez, Carmen Belén ; Campa, Daniele ; Martino, Alessandro ; Martínez-López, Joaquin ; Martínez-Bueno, Manuel ; Varkonyi, Judit ; García-Sanz, Ramón ; Jamroziak, Krzysztof ; Dumontet, Charles ; Cayuela, Andrés Jerez ; Wętek, Marzena ; Landi, Stephano ; Rossi, Anna Maria ; Lesueur, Fabienne ; Reis, Rui Manuel ; Moreno, Victor ; Marques, Herlander ; Jurczyszyn, Artur ; Andersen, Vibeke ; Vogel, Ulla ; Buda, Gabriele ; Orciuolo, Enrico ; Jacobsen, Svend E H ; Petrini, Mario ; Vangsted, Annette J ; Gemignani, Federica ; Canzian, Federico ; Jurado, Manuel ; Sainz, Juan. / Type 2 diabetes-related variants influence the risk of developing multiple myeloma : results from the IMMEnSE consortium. I: Endocrine - Related Cancer. 2015 ; Bind 22, Nr. 4. s. 545-59.
@article{ed25428b29ab475ca34afb0676a82cdb,
title = "Type 2 diabetes-related variants influence the risk of developing multiple myeloma: results from the IMMEnSE consortium",
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 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.",
author = "Rafael R{\'i}os and Lupia{\~n}ez, {Carmen Bel{\'e}n} and Daniele Campa and Alessandro Martino and Joaquin Mart{\'i}nez-L{\'o}pez and Manuel Mart{\'i}nez-Bueno and Judit Varkonyi and Ram{\'o}n Garc{\'i}a-Sanz and Krzysztof Jamroziak and Charles Dumontet and Cayuela, {Andr{\'e}s Jerez} and Marzena Wętek and Stephano Landi and Rossi, {Anna Maria} and Fabienne Lesueur and Reis, {Rui Manuel} and Victor Moreno and Herlander Marques and Artur Jurczyszyn and Vibeke Andersen and Ulla Vogel and Gabriele Buda and Enrico Orciuolo and Jacobsen, {Svend E H} and Mario Petrini and Vangsted, {Annette J} and Federica Gemignani and Federico Canzian and Manuel Jurado and Juan Sainz",
note = "{\circledC} 2015 Society for Endocrinology.",
year = "2015",
month = "8",
doi = "10.1530/ERC-15-0029",
language = "English",
volume = "22",
pages = "545--59",
journal = "Endocrine - Related Cancer",
issn = "1351-0088",
publisher = "BioScientifica Ltd.",
number = "4",

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Ríos, R, Lupiañez, CB, Campa, D, Martino, A, Martínez-López, J, Martínez-Bueno, M, Varkonyi, J, García-Sanz, R, Jamroziak, K, Dumontet, C, Cayuela, AJ, Wętek, M, Landi, S, Rossi, AM, Lesueur, F, Reis, RM, Moreno, V, Marques, H, Jurczyszyn, A, Andersen, V, Vogel, U, Buda, G, Orciuolo, E, Jacobsen, SEH, Petrini, M, Vangsted, AJ, Gemignani, F, Canzian, F, Jurado, M & Sainz, J 2015, 'Type 2 diabetes-related variants influence the risk of developing multiple myeloma: results from the IMMEnSE consortium', Endocrine - Related Cancer, bind 22, nr. 4, s. 545-59. https://doi.org/10.1530/ERC-15-0029

Type 2 diabetes-related variants influence the risk of developing multiple myeloma : results from the IMMEnSE consortium. / Ríos, Rafael; Lupiañez, Carmen Belén; Campa, Daniele; Martino, Alessandro; Martínez-López, Joaquin; Martínez-Bueno, Manuel; Varkonyi, Judit; García-Sanz, Ramón; Jamroziak, Krzysztof; Dumontet, Charles; Cayuela, Andrés Jerez; Wętek, Marzena; Landi, Stephano; Rossi, Anna Maria; Lesueur, Fabienne; Reis, Rui Manuel; Moreno, Victor; Marques, Herlander; Jurczyszyn, Artur; Andersen, Vibeke; Vogel, Ulla; Buda, Gabriele; Orciuolo, Enrico; Jacobsen, Svend E H; Petrini, Mario; Vangsted, Annette J; Gemignani, Federica; Canzian, Federico; Jurado, Manuel; Sainz, Juan.

I: Endocrine - Related Cancer, Bind 22, Nr. 4, 08.2015, s. 545-59.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Type 2 diabetes-related variants influence the risk of developing multiple myeloma

T2 - results from the IMMEnSE consortium

AU - Ríos, Rafael

AU - Lupiañez, Carmen Belén

AU - Campa, Daniele

AU - Martino, Alessandro

AU - Martínez-López, Joaquin

AU - Martínez-Bueno, Manuel

AU - Varkonyi, Judit

AU - García-Sanz, Ramón

AU - Jamroziak, Krzysztof

AU - Dumontet, Charles

AU - Cayuela, Andrés Jerez

AU - Wętek, Marzena

AU - Landi, Stephano

AU - Rossi, Anna Maria

AU - Lesueur, Fabienne

AU - Reis, Rui Manuel

AU - Moreno, Victor

AU - Marques, Herlander

AU - Jurczyszyn, Artur

AU - Andersen, Vibeke

AU - Vogel, Ulla

AU - Buda, Gabriele

AU - Orciuolo, Enrico

AU - Jacobsen, Svend E H

AU - Petrini, Mario

AU - Vangsted, Annette J

AU - Gemignani, Federica

AU - Canzian, Federico

AU - Jurado, Manuel

AU - Sainz, Juan

N1 - © 2015 Society for Endocrinology.

PY - 2015/8

Y1 - 2015/8

N2 - 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.

AB - 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.

U2 - 10.1530/ERC-15-0029

DO - 10.1530/ERC-15-0029

M3 - Journal article

VL - 22

SP - 545

EP - 559

JO - Endocrine - Related Cancer

JF - Endocrine - Related Cancer

SN - 1351-0088

IS - 4

ER -