CD44 rs13347 C>T polymorphism predicts breast cancer risk and prognosis in Chinese populations

Breast Cancer Res. 2012 Jul 12;14(4):R105. doi: 10.1186/bcr3225.

Abstract

Introduction: It has been demonstrated that the interplay of adhesion molecule CD44 and its ligands can regulate cancer cell proliferation, migration and invasion, as well as tumor-associated angiogenesis and is related to breast cancer patient survival. In this two-stage, case control study, we determined whether common functional tagSNPs (single nucleotide polymorphisms) are associated with breast cancer risk and prognosis.

Methods: Five tagSNPs of CD44 (rs10836347C>T, rs13347C>T, rs1425802A>G, rs11821102G>A, rs713330T>C) were selected and genotyped in 1,853 breast cancer patients and 1,992 healthy control subjects in Eastern and Southern populations. Potential function of rs13347C>T and association between this variation and breast cancer were further studied.

Results: Compared with the most common rs13347CC genotype, variant genotypes (CT and TT) increased an individual's susceptibility to breast cancer, especially in estrogen receptor (ER) negative patients (odds ratio (OR) = 1.37, 95%CI = 1.17 to 1.59 for ER positive patients; OR = 2.37, 95% CI = 2.00 to 2.80 for ER negative patients). We also found that rs13347CT+ TT genotypes predicts lower five-year survival rate (hazard ratio (HR) = 1.85, 95% CI = 1.09 to 3.15, P = 0.023), with the lowest survival probability in ER negative T allele carriers. Furthermore, our reporter assay findings, although preliminary and rather modest, showed that miR-509-3p may suppress CD44 expression more strongly in C allele carriers than T allele carriers (P < 0.01). Similarly, rs13347 variant genotypes (CT and TT) carriers were shown to have more CD44 expression than CC carriers in both immunohistochemistry (P < 0.001) and western blotting (P = 0.001) results.

Conclusion: These findings suggest that CD44 rs13347C>T polymorphism may affect breast cancer development and prognosis by increasing CD44 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Aged
  • Alleles
  • Asian People / genetics*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Case-Control Studies
  • China
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Hyaluronan Receptors / genetics*
  • Hyaluronan Receptors / metabolism
  • MicroRNAs / genetics
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Prognosis

Substances

  • 3' Untranslated Regions
  • Hyaluronan Receptors
  • MIRN509 microRNA, human
  • MicroRNAs