Premium
Regulatory Cytokine Gene Polymorphisms and Risk of Colorectal Carcinoma
Author(s) -
CRIVELLO ANTONINO,
GIACALONE ANTONIO,
VAGLICA MARINA,
SCOLA LETIZIA,
FORTE GIUSI IRMA,
MACALUSO MARIA CATENA,
RAIMONDI CRISTINA,
NOTO LAURA DI,
BONGIOVANNI ALBERTO,
ACCARDO ANGELA,
CANDORE GIUSEPPINA,
PALMERI LAURA,
VERNA ROBERTO,
CARUSO CALOGERO,
LIO DOMENICO,
PALMERI SERGIO
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1386.002
Subject(s) - colorectal cancer , medicine , cancer , inflammatory bowel disease , carcinogenesis , metastasis , helicobacter pylori , cytokine , oncology , immunology , cancer research , gastroenterology , disease
It is well established that cancer arises in chronically inflamed tissue, and this is particularly notable in the gastrointestinal tract. Classic examples include Helicobacter pylori –associated gastric cancer, hepatocellular carcinoma, and inflammatory bowel disease–associated colorectal cancer. Growing evidence suggests that these associations might be not casual findings. Focusing on individual cytokines has generated evidence that anti‐inflammatory cytokine interleukin (IL)‐10 and transforming growth factor‐beta1 (TGF‐β1) may have a complex role in gastrointestinal carcinogenesis. As an example, IL‐10‐deficient mice develop severe atrophic gastritis and a chronic enterocolitis, developing colorectal cancer similar to human inflammatory bowel disease–associated neoplasia. TGF‐β1 is a multifunctional signaling molecule with a wide array of roles. Animal experiments suggest that TGF‐β1 plays a biphasic role in carcinogenesis by protecting against the early formation of benign epithelial growths, but promoting a significant stimulation of tumor growth invasion and metastasis during tumor progression. We assessed association of functional polymorphisms (–1082G/A; –592C/A) and TGF‐β1 (–509C/T; +869C/T) influencing the IL‐10 production to colorectal cancer risk in a case–control study of 62 patients and 124 matched controls. No significant differences were observed among cancer patients and controls for IL‐10 –1082G/A; –592C/A genotype frequencies. Evaluation of odds ratios (OR) for the TGF‐β1 +869C/T genotypes showed a significant increased risk for individuals bearing +869CC genotype compared to +869CT‐ and +869TT‐positive individuals. These results suggest that the +869C allele, responsible for a Leu→Pro substitution in the signal peptide sequence of the TGF‐β1 protein, may have a predisposing role in the development of colorectal cancer.