Genetic variants at the miR-124 binding site on the cytoskeleton-organizing IQGAP1 gene confer differential predisposition to breast cancer

Hong Zheng, Fengju Song, Lina Zhang, Da Yang, Ping Ji, Yingmei Wang, Maria Almeida, George A. Calin, Xishan Hao, Qingyi Wei, Wei Zhang, Kexin Chen

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1151-1161
Number of pages11
JournalInternational journal of oncology
Volume38
Issue number4
DOIs
StatePublished - Apr 2011

Keywords

  • Breast cancer
  • Case-control study
  • IQGAP1
  • SNP
  • microRNA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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