viernes, 4 de junio de 2010

A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci.



Nat Genet. 2010 May 30. [Epub ahead of print]

A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci.
Bei JX, Li Y, Jia WH, Feng BJ, Zhou G, Chen LZ, Feng QS, Low HQ, Zhang H, He F, Tai ES, Kang T, Liu ET, Liu J, Zeng YX.


[1] State Key Laboratory of Oncology in Southern China, Guangzhou, China. [2] Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China. [3] These authors contributed equally to the work.

Abstract
To identify genetic susceptibility loci for nasopharyngeal carcinoma (NPC), a genome-wide association study was performed using 464,328 autosomal SNPs in 1,583 NPC affected individuals (cases) and 1,894 controls of southern Chinese descent. The top 49 SNPs from the genome-wide association study were genotyped in 3,507 cases and 3,063 controls of southern Chinese descent from Guangdong and Guangxi. The seven supportive SNPs were further confirmed by transmission disequilibrium test analysis in 279 trios from Guangdong. We identified three new susceptibility loci, TNFRSF19 on 13q12 (rs9510787, P(combined) = 1.53 x 10(-9), odds ratio (OR) = 1.20), MDS1-EVI1 on 3q26 (rs6774494, P(combined) = 1.34 x 10(-8), OR = 0.84) and the CDKN2A-CDKN2B gene cluster on 9p21 (rs1412829, P(combined) = 4.84 x 10(-7), OR = 0.78). Furthermore, we confirmed the role of HLA by revealing independent associations at rs2860580 (P(combined) = 4.88 x 10(-67), OR = 0.58), rs2894207 (P(combined) = 3.42 x 10(-33), OR = 0.61) and rs28421666 (P(combined) = 2.49 x 10(-18), OR = 0.67). Our findings provide new insights into the pathogenesis of NPC by highlighting the involvement of pathways related to TNFRSF19 and MDS1-EVI1 in addition to HLA molecules.

PMID: 20512145 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/20512145?dopt=Abstract

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