Relation between common polymorphisms in genes related to inflammatory response and colorectal cancer.
OBJECTIVE
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 alpha (TNFalpha), peroxisome proliferators-activated receptor gamma (PPARgamma), 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), TNFalpha (-308G>A), ICAM-1 (R241G and K469E), and PPARgamma (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 TNFalpha polymorphisms had no effect. Whereas the PPARgamma Pro12 genotype was associated with increased risk of disease (OR = 1.78, 95% CI: 1.25-2.49).


CONCLUSIONS
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.
Theodoropoulos
George
G
1st Propaideutic Surgical Department, Hippocration University Hospital, University of Athens, Greece.
Papaconstantinou
Ioannis
I
Felekouras
Evangelos
E
Nikiteas
Nikolaos
N
Karakitsos
Petros
P
Panoussopoulos
Dimitris
D
Lazaris
Andreas Ch
ACh
Patsouris
Efstratios
E
Bramis
John
J
Gazouli
Maria
M
D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005838:Genotype; D006115:Greece; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D015850:Interleukin-6; D016209:Interleukin-8; D047495:PPAR gamma; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1