Genetic variants and multiple myeloma risk: IMMEnSE validation of the best reported associations
A partir de données d'études précédemment publiées ainsi que sur 1 498 cas et 1 934 témoins, cette étude évalue l'association entre des polymorphismes à simple nucléotide déjà identifiés et le risque de myélome multiple
Background: Genetic background plays a role in multiple myeloma (MM) susceptibility. Several single nucleotide polymorphisms (SNPs) associated with genetic susceptibility to MM were identified in the last years, but only 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 1498 MM cases and 1934 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 MM 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 MM risk factors. Impact: Independent validations studies are crucial to identify true genetic risk factors. Our large-scale study clarifies the role of previously published polymorphisms in MM risk.