The effect of functional MAPKAPK2 copy number variation CNV-30450 on elevating nasopharyngeal carcinoma risk is modulated by EBV infection.

Abstract:

UNLABELLED: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. SUMMARY: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.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Yang L,Liu B,Qiu F,Huang B,Li Y,Huang D,Yang R,Yang X,Deng J,Jiang Q,Zhou Y,Lu J

doi

10.1093/carcin/bgt314

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

46-52

issue

1

eissn

0143-3334

issn

1460-2180

pii

bgt314

journal_volume

35

pub_type

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