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. What's New? The human WW domain-containing oxidoreductase (WWOX) gene, which regulates a wide variety of cellular functions including protein degradation, transcription, and RNA splicing, plays a vital role in tumor suppression in multiple cancers. In this study, the authors evaluated the association between copy number variations (CNV) and brain cancer risk in a large, case-control study among Chinese adults. They show a new association between a specific WWOX deletion, CNV-67048, and glioma risk in this population. These results point to CNV-67048 as a potential new biomarker for gliomas in the Chinese population © 2014 UICC.