CTLA4 gene polymorphism in Italian patients with colorectal adenoma and cancer

Colorectal cancer is a major health problem. Colonoscopic colorectal cancer screening is cumbersome and expensive. Identification of genetic risk of colorectal cancer may help to select the subjects who could benefit from colonoscopy. The immune system plays a fundamental role in the human-environment interaction, and the carcinogenic effects of many environmental factors are mediated by the chronic activation of the immune system in a genetic-controlled fashion. Cytotoxic T lymphocyte associated antigen 4 (CTLA4) plays an inhibitory role in regulating lymphocyte functions. The loss of CTLA4 function is responsible for loss of mucosal lymphocyte tolerance. The G allele at position +49 of exon 1 of the CTLA4 gene affects the CTLA4 function. We evaluated in an association study the role of CTLA4 A+49G polymorphism as a risk factor for colorectal neoplasm.

Five hundred and fifty-six patients (male 295; female 261) who underwent colonoscopy at our Centre were enrolled in the study and divided into three groups: Colorectal cancer (132 patients, M/F 68/64, mean age 66+/-11 years); Colorectal adenoma (186 patients, M/F 110/76, mean age 65+/-11 years); Healthy controls (238 patients, M/F 117/121, mean age 63+/-10 years). DNA was extracted from peripheral blood, CTLA4 gene was amplified by using specific primers, and A+49G polymorphism was analysed by restriction enzyme digestion.

No statistically significant differences in the genotype distribution among Control and Adenoma groups (p=0.93), Control and Carcinoma groups (p=0.52), and Adenoma and Carcinoma groups (p=0.53) were observed.

There is no significant correlation between CTLA4 A+49G polymorphism and the risk of colorectal neoplasm among Italian Caucasians.