TY - JOUR
T1 - Genetic variants and multiple myeloma risk
T2 - IMMEnSE validation of the best reported associations--an extensive replication of the associations from the candidate gene era
AU - Martino, Alessandro
AU - Campa, Daniele
AU - Jurczyszyn, Artur
AU - Martínez-López, Joaquín
AU - Moreno, María José
AU - Varkonyi, Judit
AU - Dumontet, Charles
AU - García-Sanz, Ramón
AU - Gemignani, Federica
AU - Jamroziak, Krzysztof
AU - Stępieł, Anna
AU - Jacobsen, Svend E Hove
AU - Andersen, Vibeke
AU - Jurado, Manuel
AU - Landi, Stefano
AU - Rossi, Anna Maria
AU - Lesueur, Fabienne
AU - Marques, Herlander
AU - Dudziłski, Marek
AU - Wątek, Marzena
AU - Moreno, Victor
AU - Orciuolo, Enrico
AU - Petrini, Mario
AU - Reis, Rui Manuel
AU - Ríos, Rafael
AU - Sainz, Juan
AU - Vogel, Ulla
AU - Buda, Gabriele
AU - Vangsted, Annette Juul
AU - Canzian, Federico
PY - 2014/4
Y1 - 2014/4
N2 - BACKGROUND: Genetic background plays a role in multiple myeloma susceptibility. Several single-nucleotide polymorphisms (SNP) associated with genetic susceptibility to multiple myeloma were identified in the last years, but only a few of them were validated in independent studies.METHODS: With the aim to conclusively validate the strongest associations so far reported, we selected the polymorphisms rs2227667 (SERPINE1), rs17501108 (HGF), rs3136685 (CCR7), rs16944 (IL1B), rs12147254 (TRAF3), rs1805087 (MTR), rs1800629 (TNF-α), rs7516435 (CASP9), rs1042265 (BAX), rs2234922 (mEH), and rs1801133 (MTHFR). We genotyped them in 1,498 multiple myeloma cases and 1,934 controls ascertained in the context of the International Multiple Myeloma rESEarch (IMMEnSE) consortium, and meta-analyzed our results with previously published ones.RESULTS: None of the selected SNPs were significantly associated with multiple myeloma risk (P value range, 0.055-0.981), possibly with the exception of the SNP rs2227667 (SERPINE1) in women.CONCLUSIONS: We can exclude that the selected polymorphisms are major multiple myeloma risk factors.IMPACT: Independent validation studies are crucial to identify true genetic risk factors. Our large-scale study clarifies the role of previously published polymorphisms in multiple myeloma risk.
AB - BACKGROUND: Genetic background plays a role in multiple myeloma susceptibility. Several single-nucleotide polymorphisms (SNP) associated with genetic susceptibility to multiple myeloma were identified in the last years, but only a few of them were validated in independent studies.METHODS: With the aim to conclusively validate the strongest associations so far reported, we selected the polymorphisms rs2227667 (SERPINE1), rs17501108 (HGF), rs3136685 (CCR7), rs16944 (IL1B), rs12147254 (TRAF3), rs1805087 (MTR), rs1800629 (TNF-α), rs7516435 (CASP9), rs1042265 (BAX), rs2234922 (mEH), and rs1801133 (MTHFR). We genotyped them in 1,498 multiple myeloma cases and 1,934 controls ascertained in the context of the International Multiple Myeloma rESEarch (IMMEnSE) consortium, and meta-analyzed our results with previously published ones.RESULTS: None of the selected SNPs were significantly associated with multiple myeloma risk (P value range, 0.055-0.981), possibly with the exception of the SNP rs2227667 (SERPINE1) in women.CONCLUSIONS: We can exclude that the selected polymorphisms are major multiple myeloma risk factors.IMPACT: Independent validation studies are crucial to identify true genetic risk factors. Our large-scale study clarifies the role of previously published polymorphisms in multiple myeloma risk.
U2 - 10.1158/1055-9965.EPI-13-1115
DO - 10.1158/1055-9965.EPI-13-1115
M3 - Journal article
C2 - 24521996
SN - 1055-9965
VL - 23
SP - 670
EP - 674
JO - Cancer Epidemiology, Biomarkers & Prevention
JF - Cancer Epidemiology, Biomarkers & Prevention
IS - 4
ER -