GWAS in the SIGNAL/PHARE clinical cohort restricts the association between the FGFR2 locus and estrogen receptor status to HER2-negative breast cancer patients

Oncotarget. 2016 Nov 22;7(47):77358-77364. doi: 10.18632/oncotarget.12669.

Abstract

Genetic polymorphisms are associated with breast cancer risk. Clinical and epidemiological observations suggest that clinical characteristics of breast cancer, such as estrogen receptor or HER2 status, are also influenced by hereditary factors. To identify genetic variants associated with pathological characteristics of breast cancer patients, a Genome Wide Association Study was performed in a cohort of 9365 women from the French nationwide SIGNAL/PHARE studies (NCT00381901/RECF1098). Strong association between the FGFR2 locus and ER status of breast cancer patients was observed (ER-positive n=6211, ER-negative n=2516; rs3135718 OR=1.34 p=5.46×10-12). This association was limited to patients with HER2-negative tumors (ER-positive n=4267, ER-negative n=1185; rs3135724 OR=1.85 p=1.16×10-11). The FGFR2 locus is known to be associated with breast cancer risk. This study provides sound evidence for an association between variants in the FGFR2 locus and ER status among breast cancer patients, particularly among patients with HER2-negative disease. This refinement of the association between FGFR2 variants and ER-status to HER2-negative disease provides novel insight to potential biological and clinical influence of genetic polymorphisms on breast tumors.

Keywords: GWAS; HER2; association; breast; estrogen receptor.

Publication types

  • Multicenter Study

MeSH terms

  • Biomarkers, Tumor*
  • Breast Neoplasms / genetics*
  • Clinical Trials, Phase III as Topic
  • Cohort Studies
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Humans
  • Polymorphism, Single Nucleotide
  • Randomized Controlled Trials as Topic
  • Receptor, ErbB-2 / genetics*
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics*
  • Receptors, Estrogen / genetics

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen
  • FGFR2 protein, human
  • Receptor, ErbB-2
  • Receptor, Fibroblast Growth Factor, Type 2