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Polymorphism and circulating levels of the chemokine CXCL12 in colorectal cancer patients

Authors:
Jan Dimberg, Anders Hugander, Sture Löfgren, Dick Wågsäter

Affiliations:
Department of Natural Science and Biomedicine, University College of Health Sciences, SE-551 11 Jönköping, Sweden. jan.dimberg@hhj.hj.se

Pages:
11-15

Abstract:

The chemokine CXCL12, also known as stromal cell-derived factor-1 (SDF-1), is a small protein that regulates leukocyte trafficking and is variably expressed in a number of normal and cancer tissues. CXCL12 as ligand and its receptor CXCR4 have been implicated in colorectal cancer (CRC) progression including angiogenesis and metastasis. A CXCL12 gene variant CXCL12-A (CXCL12-G801A, a single nucleotide polymorphism in the 3' untranslated region) is associated with increased susceptibility to breast cancer. Based on the suggested role of CXCL12 in the pathogenesis of cancer we examined the association of the gene variant CXCL12-A with CRC. The polymorphism was analysed with PCR and RFLP methods. Furthermore, the plasma CXCL12 levels from patients with CRC were also examined. There was no significant difference in genotype distribution and allelic frequencies between CRC patients (n=151) and controls (n=141). On the other hand, we found that the carrying rate of allele CXCL12-A was higher in colon cancer patients compared with rectal cancer patients (P=0.017). Analyses by ELISA showed that CRC patients (n=63) had a lower CXCL12 plasma level compared with controls (P<0.0001). Moreover, patients with tumours classified as Dukes' stage B and C revealed lower levels than patients with tumours in Dukes' stage A. Further studies with larger samples of patients are necessary to determine whether the CXCL12 polymorphism and plasma level reflect the clinical outcome of CRC and have an impact on CRC progression.

International Journal of Molecular Medicine

January 2007
Volume 19 Number 1


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