-174 G>C polymorphism of interleukin 6 gene promoter affects interleukin 6 serum level in patients with colorectal cancer.
OBJECTIVE
Experimental data suggest that interleukin 6 (IL-6) plays an important role in the development and progression of metastasis from colorectal cancer (CRC), and -174 G>C polymorphism has been identified recently in the IL-6 gene promoter. Therefore, the aim of the present study was to investigate the significance of this type of polymorphism in patients with CRC.


METHODS
Using enzyme immunoassay, IL-6 concentrations were measured in preoperative serum samples from 65 stage I-IV CRC patients. DNA was extracted from peripheral blood mononuclear cells, and -174 G>C polymorphism detected using PCR, followed by NlaIII restriction enzyme digestion and electrophoresis.


RESULTS
The median IL-6 serum level was 0.14 pg/ml in patients with stage I-III disease versus 0.41 pg/ml in patients with stage IV disease (P < 0.001). DNA amplification was possible in 62 cases. On grouping genotypes at the -174 G>C locus as C+ (CC and CG) and C- (GG), a significant association was observed between the type of polymorphism and IL-6 serum level: the median value for IL-6 was 0.14 pg/ml in C+ patients (n = 32) and 0.32 pg/ml in C- patients (n = 30; P = 0.034). Moreover, in patients with hepatic metastasis the median level of IL-6 was 0.23 pg/ml in C+ patients (n = 9) and 0.96 pg/ml in C- patients (n = 9; P = 0.004).


CONCLUSIONS
In patients with CRC, the -174 G>C polymorphism status of the IL-6 gene promoter affects the IL-6 serum level, particularly in the presence of hepatic metastasis.
Belluco
Claudio
C
Department of Oncological and Surgical Sciences, University of Padova, Padova, Italy. claudio.belluco@unipd.it
Olivieri
Fabiola
F
Bonafè
Massimiliano
M
Giovagnetti
Simona
S
Mammano
Enzo
E
Scalerta
Romano
R
Ambrosi
Alessandro
A
Franceschi
Claudio
C
Nitti
Donato
D
Lise
Mario
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
D015850:Interleukin-6