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Published on: July 3, 2013

Vitamin D receptor expression is associated with PIK3CA and KRAS mutations in colorectal cancer

Shoko Kure1, Katsuhiko Nosho, Yoshifumi Baba

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
|October 1, 2009
PubMed

Insights

Vitamin D receptor (VDR) overexpression in colorectal cancer is linked to KRAS and PIK3CA mutations. This association may influence VDR-targeted therapies and chemoprevention strategies for colon cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Vitamin D is linked to reduced risks of various cancers, including colon cancer.
  • The vitamin D receptor (VDR) is a transcription factor crucial for cell differentiation and proliferation inhibition.
  • Potential interactions between VDR and signaling pathways like RAS-MAPK and PI3K-AKT have been proposed, but their clinical relevance remains unclear.

Purpose of the Study:

  • To investigate the prognostic role of VDR expression in colorectal cancer.
  • To examine the relationship between VDR expression and PIK3CA or KRAS mutations.
  • To explore potential interactions between VDR and key cellular signaling pathways in colorectal cancer.

Main Methods:

  • VDR overexpression was assessed using immunohistochemistry in 619 colorectal cancer samples.
  • PIK3CA and KRAS mutations were analyzed via Pyrosequencing.
  • Epigenetic changes, including LINE-1 methylation and CIMP-specific promoter methylation, were evaluated using MethyLight (real-time PCR).

Main Results:

  • VDR overexpression was observed in 38% of colorectal tumors.
  • VDR overexpression was significantly associated with both KRAS (OR, 1.55) and PIK3CA (OR, 2.17) mutations, independent of other factors.
  • VDR expression showed no significant association with patient survival, prognosis, tumor stage, grade, or other molecular markers like MSI or BRAF.

Conclusions:

  • VDR overexpression in colorectal cancer is independently associated with PIK3CA and KRAS mutations.
  • These findings suggest potential interactions between VDR and the RAS-MAPK/PI3K-AKT pathways.
  • The presence of KRAS or PIK3CA mutations may influence the efficacy of VDR-targeted therapies or chemoprevention in colorectal cancer.

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