title: Regulatory cytokine gene polymorphisms and risk of colorectal carcinoma.
abstract: 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.
authors.affiliation: Patologia Clinica, Dipartimento di Biopatologia e Metodologie Biomediche, University of Palermo, Palermo, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Crivello
authors.forename: Antonio
authors.initials: A
authors.lastname: Giacalone
authors.forename: Marina
authors.initials: M
authors.lastname: Vaglica
authors.forename: Letizia
authors.initials: L
authors.lastname: Scola
authors.forename: Giusi Irma
authors.initials: GI
authors.lastname: Forte
authors.forename: Maria Catena
authors.initials: MC
authors.lastname: Macaluso
authors.forename: Cristina
authors.initials: C
authors.lastname: Raimondi
authors.forename: Laura
authors.initials: L
authors.lastname: Di Noto
authors.forename: Alberto
authors.initials: A
authors.lastname: Bongiovanni
authors.forename: Angela
authors.initials: A
authors.lastname: Accardo
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Candore
authors.forename: Laura
authors.initials: L
authors.lastname: Palmeri
authors.forename: Roberto
authors.initials: R
authors.lastname: Verna
authors.forename: Calogero
authors.initials: C
authors.lastname: Caruso
authors.forename: Domenico
authors.initials: D
authors.lastname: Lio
authors.forename: Sergio
authors.initials: S
authors.lastname: Palmeri
mesh_terms: 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*
chemical_list: D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D011392:Proline; D007930:Leucine