title: Genetic variants at the miR-124 binding site on the cytoskeleton-organizing IQGAP1 gene confer differential predisposition to breast cancer.
abstract: IQGAP1 knockout mice develop gastric cancer, but the IQGAP1 protein is associated with some advanced-stage human cancers. IQGAP1 expression is regulated by a microRNA, miR-124, through a binding site at the 3'-untranslated region, where a single nucleotide polymorphism (SNP) exists in the core binding region. We asked whether IQGAP1 expression is associated with breast cancer development and whether genetic variants at the miR-124 binding site are important. We genotyped the IQGAP1 SNP rs1042538 A/T in 1,541 breast cancer cases and 1,598 controls and analyzed the frequency of the variant and interactions with major risk factors in these populations. We also measured the expression of IQGAP1 at both mRNA and protein levels in different IQGAP1 genotypes. The IQGAP1 TT genotype, compared with the AA genotype, was associated with a significantly lower risk of developing breast cancer [P=0.049, odds ratio (OR), 0.78; 95% confidence interval (CI), 0.61-0.99]. In case-only analyses, the TT, compared with the AA, genotype was associated with progesterone receptor-positive subjects (OR, 1.35; 95% CI, 1.00-1.83). The expression levels of IQGAP1 protein were significantly higher in the TT genotype compated to the AA genotype. The presence of SNPs at the miR-124 binding site may be a marker for predicting breast cancer risk and prognosis.
authors.affiliation: Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Hospital and Institute, Tianjin, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.forename: Fengju
authors.initials: F
authors.lastname: Song
authors.forename: Lina
authors.initials: L
authors.lastname: Zhang
authors.forename: Da
authors.initials: D
authors.lastname: Yang
authors.forename: Ping
authors.initials: P
authors.lastname: Ji
authors.forename: Yingmei
authors.initials: Y
authors.lastname: Wang
authors.forename: Maria
authors.initials: M
authors.lastname: Almeida
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
authors.forename: Xishan
authors.initials: X
authors.lastname: Hao
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Kexin
authors.initials: K
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000818:Animals; D044466:Asian People; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008207:Lymphatic Metastasis; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D034622:RNA Interference; D047368:Tumor Burden; D020703:ras GTPase-Activating Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C101203:IQ motif containing GTPase activating protein 1; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D020703:ras GTPase-Activating Proteins