title: Roles of functional NFKB1 and β-TrCP insertion/deletion polymorphisms in mRNA expression and epithelial ovarian cancer susceptibility.
abstract: Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecological cancers. Nuclear factor-kappa B (NF-κB) is involved in carcinogenesis and in the development of EOC. The β-transducin repeat-containing protein (β-TrCP) is a positive regulator of the NF-κB signaling pathway. Recent studies have indicated that the -94 ins/del ATTG polymorphism in the promoter region of the NFKB1 gene, and the 9N ins/del polymorphism in the 3'-untranslated region of the β-TrCP gene are associated with increased susceptibility to a variety of cancers. We examined a potential association between these two polymorphisms and EOC. Genotypes were determined for 187 patients with EOC and 221 healthy control subjects, using the MassARRAY system. We found a significant association between the -94 ins/del ATTG genotype distribution and EOC. The frequency of the -94 del ATTG allele was significantly lower in EOC patients compared to healthy controls. The NF-κB mRNA level in cancer tissue was significantly correlated with -94 ins/del ATTG genotypes. Compared to the ATTG1/ATTG1 phenotype, the NF-κB mRNA level was 2.089 and 1.257 times higher in the ATTG2 (insertion)/ATTG2 homozygote and the ATTG1 (deletion)/ATTG2 heterozygote, respectively. However, we found no evidence of association between the 9N ins/del polymorphism of the β-TrCP gene and EOC in this Chinese population. Based on these results, we suggest that the NF-κB -94 ins/del ATTG polymorphism is a risk factor for EOC susceptibility.
authors.affiliation: Key Laboratory of Fertility Preservation and Maintenance, Ningxia Medical University, Ministry of Education, Yinchuan, Ningxia, China.
authors.forename: Z H
authors.initials: ZH
authors.lastname: Huo
authors.forename: H J
authors.initials: HJ
authors.lastname: Zhong
authors.forename: Y S
authors.initials: YS
authors.lastname: Zhu
authors.forename: B
authors.initials: B
authors.lastname: Xing
authors.forename: H
authors.initials: H
authors.lastname: Tang
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D054643:INDEL Mutation; D008875:Middle Aged; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D044844:beta-Transducin Repeat-Containing Proteins / Q000235:genetics*
chemical_list: D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D012333:RNA, Messenger; D044844:beta-Transducin Repeat-Containing Proteins