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

Alessandro Martino, Daniele Campa, Artur Jurczyszyn, Joaquín Martínez-López, María José Moreno, Judit Varkonyi, Charles Dumontet, Ramón García-Sanz, Federica Gemignani, Krzysztof Jamroziak, Anna Stępieł, Svend E Hove Jacobsen, Vibeke Andersen, Manuel Jurado, Stefano Landi, Anna Maria Rossi, Fabienne Lesueur, Herlander Marques, Marek Dudziłski, Marzena WątekVictor Moreno, Enrico Orciuolo, Mario Petrini, Rui Manuel Reis, Rafael Ríos, Juan Sainz, Ulla Vogel, Gabriele Buda, Annette Juul Vangsted, Federico Canzian

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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.

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  • Cite this

    Martino, A., Campa, D., Jurczyszyn, A., Martínez-López, J., Moreno, M. J., Varkonyi, J., Dumontet, C., García-Sanz, R., Gemignani, F., Jamroziak, K., Stępieł, A., Jacobsen, S. E. H., Andersen, V., Jurado, M., Landi, S., Rossi, A. M., Lesueur, F., Marques, H., Dudziłski, M., ... Canzian, F. (2014). Genetic variants and multiple myeloma risk: IMMEnSE validation of the best reported associations--an extensive replication of the associations from the candidate gene era. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 23(4), 670-674. https://doi.org/10.1158/1055-9965.EPI-13-1115