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Genetic variants and multiple myeloma risk: IMMEnSE validation of the best reported associations--an extensive replication of the associations from the candidate gene era.

Authors: Martino, A  Campa, D  Jurczyszyn, A  Martinez-Lopez, J  Moreno, MJ  Varkonyi, J  Dumontet, C  Garcia-Sanz, R  Gemignani, F  Jamroziak, K  Stepiel, A  Jacobsen, SE  Andersen, V  Jurado, M  Landi, S  Rossi, AM  Lesueur, F  Marques, H  Dudzinski, M  Watek, M  Moreno, V  Orciuolo, E  Petrini, M  Reis, RM  Rios, R  Sainz, J  Vogel, U  Buda, G  Vangsted, AJ  Canzian, F 
Citation: Martino A, etal., Cancer Epidemiol Biomarkers Prev. 2014 Apr;23(4):670-4. doi: 10.1158/1055-9965.EPI-13-1115. Epub 2014 Feb 12.
Pubmed: (View Article at PubMed) PMID:24521996
DOI: Full-text: DOI:10.1158/1055-9965.EPI-13-1115

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-alpha), 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.


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CRRD Object Information
CRRD ID: 11252122
Created: 2016-06-24
Species: All species
Last Modified: 2016-06-24
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.