title: Association study of a functional copy number variation in the WWOX gene with risk of gliomas among Chinese people.
abstract: 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.
authors.affiliation: Department of Neurology, Chengdu Military General Hospital, Chengdu, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yu
authors.forename: Jin
authors.initials: J
authors.lastname: Fan
authors.forename: Xin
authors.initials: X
authors.lastname: Ding
authors.forename: CongYang
authors.initials: C
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiang
authors.forename: Qing Song
authors.initials: QS
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D010088:Oxidoreductases / Q000235:genetics*; D011379:Prognosis; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D000074584:WW Domain-Containing Oxidoreductase
chemical_list: D025521:Tumor Suppressor Proteins; D004247:DNA; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human
keywords: WWOX; copy number variation; genetic susceptibility; gliomas