Regulatory cytokine gene polymorphisms and risk of colorectal carcinoma.
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-beta1) 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-beta1 is a multifunctional signaling molecule with a wide array of roles. Animal experiments suggest that TGF-beta1 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-beta1 (-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-beta1 +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-beta1 protein, may have a predisposing role in the development of colorectal cancer.
Crivello
Antonino
A
Patologia Clinica, Dipartimento di Biopatologia e Metodologie Biomediche, University of Palermo, Palermo, Italy.
Giacalone
Antonio
A
Vaglica
Marina
M
Scola
Letizia
L
Forte
Giusi Irma
GI
Macaluso
Maria Catena
MC
Raimondi
Cristina
C
Di Noto
Laura
L
Bongiovanni
Alberto
A
Accardo
Angela
A
Candore
Giuseppina
G
Palmeri
Laura
L
Verna
Roberto
R
Caruso
Calogero
C
Lio
Domenico
D
Palmeri
Sergio
S
D000483:Alleles; D019943:Amino Acid Substitution; D002277:Carcinoma / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D007558:Italy; D007930:Leucine / Q000737:chemistry / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011392:Proline / Q000737:chemistry / Q000235:genetics; D012306:Risk; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D011392:Proline; D007930:Leucine