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World J Gastroenterol. Aug 21, 2006; 12(31): 5037-5043
Published online Aug 21, 2006. doi: 10.3748/wjg.v12.i31.5037
Relation between common polymorphisms in genes related to inflammatory response and colorectal cancer
George Theodoropoulos, Ioannis Papaconstantinou, Evangelos Felekouras, Nikolaos Nikiteas, Petros Karakitsos, Dimitris Panoussopoulos, Andreas Ch Lazaris, Efstratios Patsouris, John Bramis, Maria Gazouli
George Theodoropoulos, Dimitris Panoussopoulos, John Bramis, 1st Propaideutic Surgical Department, Hippocration University Hospital, School of Medicine, University of Athens, Greece
Ioannis Papaconstantinou, 1st Surgical Department, Laikon University Hospital, University of Athens, Greece
Nikolaos Nikiteas, 2nd Propaideutic Surgical Department, Laikon University Hospital, University of Athens, Greece
Petros Karakitsos, Department of Cytopathology, University General Hospital “Attikon”, University of Athens, Greece
Andreas Ch Lazaris, Efstratios Patsouris, Department of Pathology, School of Medicine, University of Athens, Greece
Maria Gazouli, Department of Biology, School of Medicine, University of Athens, Greece
Author contributions: All authors contributed equally to the work.
Correspondence to: Maria Gazouli, PhD, Michalakopoulou 176, Goudi 11725, Athens, Greece. mgazouli@med.uoa.gr
Telephone: +30-210-7462231 Fax: +30-210-7462340
Received: February 28, 2006
Revised: March 13, 2006
Accepted: March 20, 2006
Published online: August 21, 2006
Abstract

AIM: To investigate the association between common single nucleotide polymorphisms (SNPs) in inflammatory response-related genes such as interleukin (IL)-6, IL-8, tumor necrosis factor α (TNFα), peroxisome proliferators-activated receptor γ (PPARγ), intercellular adhesion molecule-1 (ICAM-1) and the risk of colorectal cancer (CRC) in a group of Greek patients.

METHODS: The study group consisted of 222 CRC patients and 200 healthy controls. Genotyping was performed using allele-specific PCR of PRC-RFLP and the results were confirmed by sequencing. We studied the association of SNPs in the IL-6 (-174G > C), IL-8 (-251T > A), TNFα (-308G > A), ICAM-1 (R241G and K469E), and PPARγ (Pro12Ala) genes and the risk of CRC.

RESULTS: The IL-6 -174G, R241 and K469 alleles of ICAM-1 were associated with increased risk of CRC (OR = 1.77, 95% CI: 1.34-2.34; OR = 1.83, 95% CI: 1.23-2.72; and OR = 1.35, 95% CI: 1.03-1.77 respectively). The IL-8 and TNFα polymorphisms had no effect. Whereas the PPARγ Pro12 genotype was associated with increased risk of disease (OR = 1.78, 95% CI: 1.25-2.49).

CONCLUSION: The association between common SNPs in immunologic response-related genes and CRC is reported in the present study. Apart from shedding light on the mechanisms of malignancy initiation and progression, SNPs may improve appropriate screening for sub-populations at risk.

Keywords: Colorectal cancer, Inflammation, Single nucleotide polymorphisms