The effect of functional MAPKAPK2 copy number variation CNV-30450 on elevating nasopharyngeal carcinoma risk is modulated by EBV infection.
Mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK2) is recognized as oncogenic and simulative role on tumorigenesis by virtue of abnormal expression in cancer including nasopharyngeal carcinoma (NPC). We hypothesized that the copy number variation (CNV)-30450, which duplicates the MAPKAPK2 promoter, may affect MAPKAPK2 expression and be associated with NPC risk. In two independent case-control panels of southern and eastern Chinese with a total of 1590 NPC patients and 1979 cancer-free controls, we investigated the association between CNV-30450 and NPC risk by genotyping the CNV-30450 with the TaqMan assay, and tested its biological effect. Consistent findings were observed in the two populations, that the increased copy number of CNV-30450 was associated with increased risk of NPC (3/4-copy versus 2-copy: odds ratio = 1.28, 95% confidence interval = 1.10-1.49), in which lies a biological mechanism that the adverse genotypes enhanced the promoter activity of MAPKAPK2 and elevated MAPKAPK2 expression. Moreover, the CNV-30450 adverse genotypes significantly interacted with Epstein-Barr virus (EBV) infection on increasing NPC risk (P = 0.035), and the genotype-phenotype correlation was only significant in EBV-positive cases (P = 0.037) but not in EBV-negative ones (P = 0.366). These data suggest that the functional CNV-30450 in the MAPKAPK2 promoter elevates the NPC risk with a modulation by EBV infection, which may be an indicator of susceptibility to NPC.


CONCLUSIONS
This case-control study suggests that the functional CNV-30450 in the MAPKAPK2 promoter elevates the NPC risk with a modulation by EBV infection, which may be an indicator of susceptibility to NPC.
The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, People's Republic of China.
Lei
L
Yang
Bin
B
Liu
Fuman
F
Qiu
Binfang
B
Huang
Yinyan
Y
Li
Dongsheng
D
Huang
Rongrong
R
Yang
Xiaorong
X
Yang
Jieqiong
J
Deng
Qingping
Q
Jiang
Yifeng
Y
Zhou
Jiachun
J
Lu
D044466:Asian People / Q000235:genetics; D002277:Carcinoma; D016022:Case-Control Studies; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000821:virology*; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000099190:MAP-Kinase-Activated Kinase 2
D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D000099190:MAP-Kinase-Activated Kinase 2