title: Genetic variants and multiple myeloma risk: IMMEnSE validation of the best reported associations--an extensive replication of the associations from the candidate gene era.
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.
  
  
  CONCLUSIONS
  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.
authors: Authors' Affiliations: Genomic Epidemiology Group, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Hematology, Cracow University Hospital, Cracow; Medical University of Łodz; Laboratory of Clinical and Transplant Immunology and Genetics, Copernicus Memorial Hospital, Łodz; Rzeszow Regional Hospital, Rzeszow; Holycross Cancer Center, Kielce, Poland; Department of Hematology, Hospital Universitario Doce de Octubre, Madrid; Morales Meseguer General University Hospital, Murcia; University Hospital of Salamanca, Salamanca; Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government; Hematology Department, Virgen de las Nieves University Hospital, Granada; IDIBELL-Catalan Institute of Oncology, University of Barcelona, Barcelona, Spain; Semmelweis University, Budapest, Hungary; Institut National de la Santé et de la Recherche Medicale (INSERM) UMR 1052/CNRS 5286, Université Claude Bernard Lyon I, Lyon; Genetic Epidemiology of Cancer team, INSERM, U900, Institut Curie, Mines ParisTech, Paris, France; Department of Biology, University of Pisa, Pisa, Italy; Clinic of Immunology, Laboratory Center, Hospital of Southern Jutland, Sønderborg; Organ Center, Hospital of Southern Jutland, Aabenraa; Institute of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense C; National Research Centre for the Working Environment, Copenhagen; Roskilde Hospital, Copenhagen University, Roskilde, Denmark; Life and Health Sciences Research Institute, University of Minho, Braga; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal; UO Hematology, Department of Internal and Experimental Medicine, University of Pisa, Pisa, Italy; and Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.
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mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors