Polymorphic CAG Repeat and Protein Expression of Androgen Receptor Gene in Colorectal Cancer

Mol Cancer Ther. 2015 Apr;14(4):1066-74. doi: 10.1158/1535-7163.MCT-14-0620. Epub 2015 Jan 30.

Abstract

Although somatic alterations in CAG repeats in the androgen receptor (AR) gene have been suggested to predispose to colorectal cancer, less is known about AR in colorectal cancer carcinogenesis. Because of lack of relevant analysis on CAG repeat length and AR expression in colorectal cancer, we aimed to investigate the prognostic value of polymorphic CAG and protein expression of the AR gene in patients with colorectal cancer. A case-control study was carried out on 550 patients with colorectal cancer and 540 healthy controls to investigate whether polymorphic CAG within the AR gene is linked to increased risk for colorectal cancer. Polymorphic CAG and AR expression were analyzed to clarify their relationship with clinicopathologic and prognostic factors in patients with colorectal cancer. The study showed that the AR gene in patients with colorectal cancer had a longer CAG repeat sequence than those in the control group, as well as increased risk for colorectal cancer among females (P = 0.013), males (P = 0.002), and total colorectal cancer population (P < 0.001), respectively. AR expression exhibited a significant difference in long CAG repeat sequence among males (P < 0.001), females (P < 0.001), and total colorectal cancer study population (P < 0.001). Both long CAG repeat sequence and negative AR expression were associated with a short 5-year overall survival (OS) rate in colorectal cancer. Long CAG repeat sequences and the absence of AR expression were closely related to the development of colorectal cancer. Both long CAG and decreased AR expression were correlated with the poor 5-year OS in patients with colorectal cancer.

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Polymorphism, Genetic*
  • Prognosis
  • Receptors, Androgen / genetics*
  • Receptors, Androgen / metabolism*
  • Trinucleotide Repeat Expansion
  • Trinucleotide Repeats*
  • Tumor Burden

Substances

  • Receptors, Androgen