Association of single nucleotide polymorphisms in FGF-RAS/MAP signalling cascade with breast cancer susceptibility

Gen Physiol Biophys. 2017 Dec;36(5):565-572. doi: 10.4149/gpb_2017033.

Abstract

The fibroblast growth factor receptors (FGFRs) and Ras/mitogen activated protein (RAS/MAP) signalling cascades are the main molecular pathways involved in breast carcinogenesis. This study aims to determine the association between FGF10 (rs4415084 C>T), FGFR2 (rs2981582 C>T) and MAP3K1 (rs889312 A>C) gene polymorphisms and breast cancer, to analyse the discriminative ability of each SNP and to test the accuracy of the predictive breast cancer risk model which includes all SNPs. We conducted a case-control study of 170 women (57.06 ± 11.60 years) with histologically confirmed breast cancer and 146 controls (50.24 ± 10.69 years). High resolution melting (HRM) method with Sanger sequencing validation was used in analyses. We have revealed significant association of FGFR2 and MAP3K1 polymorphisms with breast cancer. The odds ratio of FGFR2 T allele was 1.897 (95% CI 1.231-2.936, p = 0.004) and MAP3K1 C allele 1.804 (95% CI 1.151-2.845, p = 0.012). FGFR2 polymorphism achieved the best discriminative ability (41.95%). The Random Forest algorithm selected FGFR2, MAP3K1 and age as important breast cancer predictors. The accuracy of this prediction model approached moderate accuracy (70%), with 35.9% sensitivity and 88.6% specificity.

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Female
  • Fibroblast Growth Factor 10 / genetics*
  • Genetic Association Studies
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Incidence
  • MAP Kinase Kinase Kinase 1 / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics*
  • Reproducibility of Results
  • Risk Assessment / methods
  • Sensitivity and Specificity
  • Signal Transduction / genetics
  • Slovakia / epidemiology

Substances

  • Biomarkers, Tumor
  • FGF10 protein, human
  • Fibroblast Growth Factor 10
  • Genetic Markers
  • FGFR2 protein, human
  • Receptor, Fibroblast Growth Factor, Type 2
  • MAP Kinase Kinase Kinase 1
  • MAP3K1 protein, human