Regulatory Cytokine Gene Polymorphisms and Risk of Colorectal Carcinoma

• Published in: Annals of the New York Academy of Sciences 2006-11, Vol.1089 (1), p.98-103
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Alleles; Amino Acid Substitution; Carcinoma - genetics; Case-Control Studies; colorectal cancer; Colorectal Neoplasms - genetics; Female; Gene Frequency; gene polymorphisms; Genetic Predisposition to Disease; Helicobacter; Humans; IL-10; Interleukin-10 - genetics; Italy; Leucine - chemistry; Leucine - genetics; Male; Polymorphism, Single Nucleotide; Proline - chemistry; Proline - genetics; Risk; TGF-β1; Transforming Growth Factor beta1 - genetics
• ISSN: 0077-8923; 1749-6632; 1930-6547
• DOI: 10.1196/annals.1386.002

:  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.