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Analysis of single nucleotide polymorphism in the promoter and protein expression of the chemokine eotaxin-1 in colorectal cancer patients.

AbstractBACKGROUND:
Previous studies suggest that chemokines (chemotactic cytokines) promote and regulate neoplastic progression including metastasis and angiogenesis. The chemokine eotaxin-1 is a powerful eosinophil attractant but also exerts chemotaxis of other leukocytes. Eotaxin-1 has been implicated in gastrointestinal disorders and may play an important role in colorectal mucosal immunity.
PATIENTS AND METHODS:
The objective of this study was to assess the role of eotaxin-1 in colorectal cancer (CRC). Levels of eotaxin-1 protein in CRC tissues (n = 86) and paired normal mucosa were compared after determination by ELISA. Plasma eotaxin-1 levels from CRC patients (n = 67) were also compared with controls (n = 103) using the same method. Moreover, a TaqMan system was used to evaluate the -384A>G eotaxin-1 gene variant in CRC patients (n = 241) and in a control group (n = 253).
RESULTS:
Eotaxin-1 protein levels in colorectal tumours were significantly (P < 0.0001) higher than in normal tissue. Immunohistochemistry revealed eotaxin-1 expression in stromal cells such as fibroblasts and leukocytes of the CRC tissue. The plasma eotaxin-1 level in CRC patients was lower compared with controls (P < 0.0001). Patients with tumours classified as Dukes' stage B and C had lower levels than patients with tumours in Dukes' stage A. We found no difference in genotype distribution but noted a difference regarding allele distribution (P = 0.036) and a dominance of allele G in rectal cancer patients.
CONCLUSION:
The up-regulated eotaxin-1 protein expression in cancer tissue may reflect an eotaxin-1 mediated angiogenesis and/or a recruitment of leukocytes with potential antitumourigenic role. We noticed a dominance of the G allele in rectal cancer patients compared with colon cancer patients that was independent of eotaxin-1 expression.
AuthorsDick Wågsäter, Sture Löfgren, Anders Hugander, Olaf Dienus, Jan Dimberg
JournalWorld journal of surgical oncology (World J Surg Oncol) Vol. 5 Pg. 84 (Jul 31 2007) ISSN: 1477-7819 [Electronic] England
PMID17672898 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Chemokine CCL11
Topics
  • Adenocarcinoma (genetics, metabolism)
  • Adult
  • Aged
  • Aged, 80 and over
  • Chemokine CCL11 (genetics, metabolism)
  • Colorectal Neoplasms (genetics, metabolism)
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic (drug effects, genetics)
  • Up-Regulation

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