A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci.
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, Pcombined=1.53x10(-9), odds ratio (OR)=1.20), MDS1-EVI1 on 3q26 (rs6774494, Pcombined=1.34x10(-8), OR=0.84) and the CDKN2A-CDKN2B gene cluster on 9p21 (rs1412829, Pcombined=4.84x10(-7), OR=0.78). Furthermore, we confirmed the role of HLA by revealing independent associations at rs2860580 (Pcombined=4.88x10(-67), OR=0.58), rs2894207 (Pcombined=3.42x10(-33), OR=0.61) and rs28421666 (Pcombined=2.49x10(-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.
State Key Laboratory of Oncology in Southern China, Guangzhou, China.
Jin-Xin
JX
Bei
Yi
Y
Li
Wei-Hua
WH
Jia
Bing-Jian
BJ
Feng
Gangqiao
G
Zhou
Li-Zhen
LZ
Chen
Qi-Sheng
QS
Feng
Hui-Qi
HQ
Low
Hongxing
H
Zhang
Fuchu
F
He
E Shyong
ES
Tai
Tiebang
T
Kang
Edison T
ET
Liu
Jianjun
J
Liu
Yi-Xin
YX
Zeng
D044466:Asian People / Q000235:genetics; D002681:China; D004268:DNA-Binding Proteins / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D000074008:MDS1 and EVI1 Complex Locus Protein; D009303:Nasopharyngeal Neoplasms / Q000208:ethnology / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011519:Proto-Oncogenes / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics
D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D009363:Neoplasm Proteins; D018124:Receptors, Tumor Necrosis Factor; C411850:TNFRSF19 protein, human; D014157:Transcription Factors