基因变异与多发性骨髓瘤风险：对已报道最佳关联的IMMEnSE验证——候选基因时代关联的广泛重复研究
Genetic variants and multiple myeloma risk: IMMEnSE validation of the best reported associations--an extensive replication of the associations from the candidate gene era.
作者信息
Martino Alessandro, Campa Daniele, Jurczyszyn Artur, Martínez-López Joaquín, Moreno María José, Varkonyi Judit, Dumontet Charles, García-Sanz Ramón, Gemignani Federica, Jamroziak Krzysztof, Stępieł Anna, Jacobsen Svend E Hove, Andersen Vibeke, Jurado Manuel, Landi Stefano, Rossi Anna Maria, Lesueur Fabienne, Marques Herlander, Dudziński Marek, Wątek Marzena, Moreno Victor, Orciuolo Enrico, Petrini Mario, Reis Rui Manuel, Ríos Rafael, Sainz Juan, Vogel Ulla, Buda Gabriele, Vangsted Annette Juul, Canzian Federico
机构信息
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.
出版信息
Cancer Epidemiol Biomarkers Prev. 2014 Apr;23(4):670-4. doi: 10.1158/1055-9965.EPI-13-1115. Epub 2014 Feb 12.
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.
背景
遗传背景在多发性骨髓瘤易感性中起作用。近年来，已鉴定出几种与多发性骨髓瘤遗传易感性相关的单核苷酸多态性（SNP），但其中只有少数在独立研究中得到验证。
方法
为了最终验证迄今为止报道的最强关联，我们选择了多态性rs2227667（SERPINE1）、rs17501108（HGF）、rs3136685（CCR7）、rs16944（IL1B）、rs12147254（TRAF3）、rs1805087（MTR）、rs1800629（TNF-α）、rs7516435（CASP9）、rs1042265（BAX）、rs2234922（mEH）和rs1801133（MTHFR）。我们在国际多发性骨髓瘤研究（IMMEnSE）联盟的背景下，对1498例多发性骨髓瘤病例和1934例对照进行了基因分型，并将我们的结果与先前发表的结果进行了荟萃分析。
结果
所选的SNP均与多发性骨髓瘤风险无显著关联（P值范围为0.055 - 0.981），女性中的SNP rs2227667（SERPINE1）可能除外。
结论
我们可以排除所选多态性是多发性骨髓瘤的主要风险因素。
影响
独立验证研究对于识别真正的遗传风险因素至关重要。我们的大规模研究阐明了先前发表的多态性在多发性骨髓瘤风险中的作用。
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