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Association study of a functional copy number variation in the WWOX gene with risk of gliomas among Chinese people
Author(s) -
Yu Ke,
Fan Jin,
Ding Xin,
Li CongYang,
Wang Jun,
Xiang Yang,
Wang Qing Song
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28815
Subject(s) - wwox , glioma , copy number variation , chromosomal fragile site , biology , gene , tumor suppressor gene , cancer research , genotype , suppressor , genetics , carcinogenesis , chromosome , genome
Gliomas represents more than 80% of all malignant brain tumors. However, the etiology still remains largely unknown. Human WW domain‐containing oxidoreductase ( WWOX ), which is located at 16q23.1–16q23.2, the common fragile site 16D ( FRA16D ), an area with a high frequency of gene deletions or chromosomal alterations, has been identified as a tumor suppressor gene in multiple cancers. In current study, we analyzed the WWOX deletion (CNV‐67048) in a large, case–control study of 3,622 adult Chinese people (including 1,798 glioma cases and 1,824 healthy controls). All participants were genotyped using real‐time qualitative PCR (qPCR), and its biological effect was validated with mRNA expression assays. The deletion was significantly associated with glioma risk, with ORs (95% CIs) of 1.21 (1.05–1.41) associated with 1 copy deletion and 1.94 (1.37–2.75) associated with 2 copy deletion as compared with subjects with no deletion ( p for trend = 8.05 × 10 −6 ). Additional adjustments and stratified analyses did not change the results materially. The mRNA levels of WWOX in glioma tissues were significantly lower than that of their border tissues ( p = 0.007), especially in the loss genotyped subjects. Our data suggest that the loss genotypes of CNV‐67048 in WWOX gene predispose their carriers to gliomas, and WWOX gene deletion may be a new biomarker for predicting risk of gliomas.