Susceptibility loci associated with specific and shared subtypes of lymphoid malignancies.

Autor: Joseph Vijai, Tomas Kirchhoff, Kasmintan A Schrader, Jennifer Brown, Ana Virginia Dutra-Clarke, Christopher Manschreck, Nichole Hansen, Rohini Rau-Murthy, Kara Sarrel, Jennifer Przybylo, Sohela Shah, Srujana Cheguri, Zsofia Stadler, Liying Zhang, Ora Paltiel, Dina Ben-Yehuda, Agnes Viale, Carol Portlock, David Straus, Steven M Lipkin, Mortimer Lacher, Mark Robson, Robert J Klein, Andrew Zelenetz, Kenneth Offit
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: PLoS Genetics, Vol 9, Iss 1, p e1003220 (2013)
Druh dokumentu: article
ISSN: 1553-7390
1553-7404
DOI: 10.1371/journal.pgen.1003220
Popis: The genetics of lymphoma susceptibility reflect the marked heterogeneity of diseases that comprise this broad phenotype. However, multiple subtypes of lymphoma are observed in some families, suggesting shared pathways of genetic predisposition to these pathologically distinct entities. Using a two-stage GWAS, we tested 530,583 SNPs in 944 cases of lymphoma, including 282 familial cases, and 4,044 public shared controls, followed by genotyping of 50 SNPs in 1,245 cases and 2,596 controls. A novel region on 11q12.1 showed association with combined lymphoma (LYM) subtypes. SNPs in this region included rs12289961 near LPXN, (P(LYM) = 3.89×10(-8), OR = 1.29) and rs948562 (P(LYM) = 5.85×10(-7), OR = 1.29). A SNP in a novel non-HLA region on 6p23 (rs707824, P(NHL) = 5.72×10(-7)) was suggestive of an association conferring susceptibility to lymphoma. Four SNPs, all in a previously reported HLA region, 6p21.32, showed genome-wide significant associations with follicular lymphoma. The most significant association with follicular lymphoma was for rs4530903 (P(FL) = 2.69×10(-12), OR = 1.93). Three novel SNPs near the HLA locus, rs9268853, rs2647046, and rs2621416, demonstrated additional variation contributing toward genetic susceptibility to FL associated with this region. Genes implicated by GWAS were also found to be cis-eQTLs in lymphoblastoid cell lines; candidate genes in these regions have been implicated in hematopoiesis and immune function. These results, showing novel susceptibility regions and allelic heterogeneity, point to the existence of pathways of susceptibility to both shared as well as specific subtypes of lymphoid malignancy.
Databáze: Directory of Open Access Journals
Externí odkaz: