title: WWOX CNV-67048 Functions as a Risk Factor for Epithelial Ovarian Cancer in Chinese Women by Negatively Interacting with Oral Contraceptive Use.
abstract: Copy number variations (CNVs) have attracted increasing evidences to represent their roles as cancer susceptibility regulators. However, little is known about the role of CNV in epithelia ovarian cancer (EOC). Recently, the CNV-67048 of WW domain-containing oxidoreductase (WWOX) was reported to alter cancer risks. Considering that WWOX also plays a role in EOC, we hypothesized that the CNV-67048 was associated with EOC risk. In a case-control study of 549 EOC patients and 571 age (±5 years) matched cancer-free controls, we found that the low copy number of CNV-67048 (1-copy and 0-copy) conferred a significantly increased risk of EOC (OR = 1.346, 95% CI = 1.037-1.747) and it determined the risk by means of copy number-dependent dosage effect (P = 0.009). Data from TCGA also confirmed the abovementioned association as the frequency of low copies in EOC group was 3.68 times more than that in healthy group (P = 0.023). The CNV also negatively interacted with oral contraceptive use on EOC risk (P = 0.042). Functional analyses further showed a lower mRNA level of WWOX in tissues with the 0-copy or 1-copy than that in those with the 2-copy (P = 0.045). Our data suggested the CNV-67048 to be a risk factor of EOC in Chinese women.
authors.affiliation: Gynecology Department, Guangdong Women and Children Hospital, No. 521, Xingnan Road, Panyu District, Guangzhou 511442, China.
authors.forename: Yongxiu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Gynecology Department, Guangdong Women and Children Hospital, No. 521, Xingnan Road, Panyu District, Guangzhou 511442, China.
authors.forename: Xiaochang
authors.initials: X
authors.lastname: Tan
authors.affiliation: Gynecology Department, Guangdong Women and Children Hospital, No. 521, Xingnan Road, Panyu District, Guangzhou 511442, China.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Gynecology Department, Guangdong Women and Children Hospital, No. 521, Xingnan Road, Panyu District, Guangzhou 511442, China.
authors.forename: Bi
authors.initials: B
authors.lastname: Mai
authors.affiliation: Gynecology Department, Guangdong Women and Children Hospital, No. 521, Xingnan Road, Panyu District, Guangzhou 511442, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Huang
authors.affiliation: Gynecology Department, Guangdong Women and Children Hospital, No. 521, Xingnan Road, Panyu District, Guangzhou 511442, China.
authors.forename: Guiying
authors.initials: G
authors.lastname: Hu
authors.affiliation: Gynecology Department, Guangdong Women and Children Hospital, No. 521, Xingnan Road, Panyu District, Guangzhou 511442, China.
authors.forename: Xiping
authors.identifier: 0000-0002-6730-7184
authors.initials: X
authors.lastname: Luo
mesh_terms: D000368:Aged; D000077216:Carcinoma, Ovarian Epithelial; D003276:Contraceptives, Oral / Q000009:adverse effects*; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D010088:Oxidoreductases / Q000235:genetics*; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D000074584:WW Domain-Containing Oxidoreductase
chemical_list: D003276:Contraceptives, Oral; D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human