Background: CTLA4  is a candidate gene which has been implicated in the development of colorectal cancer (CRC).
Patients and Methods: To determine the important role of CTLA-4  polymorphisms on risk of CRC, we genotyped four CTLA-4  tagging polymorphisms and calculated crude/adjusted ORs with their 95% CIs. We recruited 1,003 sporadic CRC cases and 1,303 controls.
Results: The findings suggested that CTLA-4 rs231775 G>A polymorphism increased the risk of CRC (homozygote model: adjusted OR=1.40, 95% CI=1.05–1.87, P =0.022; dominant model: adjusted OR=1.19, 95% CI=1.00–1.41, P =0.047; and recessive model: adjusted OR=1.38, 95% CI=1.05–1.82, P =0.021). In a stratified analysis by site of tumor, this association was also found in colon cancer. We also found that CTLA-4  rs231775 GA/AA genotypes might be associated with an increased risk of CRC in Zhenjiang cohort. In addition, we found the CTLA-4 rs16840252 C>T polymorphism was associated with the risk of colon cancer. Haplotype comparison analysis showed that CTLA-4 G_rs3087243C_rs16840252C_rs733618A_rs231775, G_rs3087243C_rs16840252T_rs733618A_rs231775, and other haplotypes increased the risk of CRC (P <0.001, <0.001, and 0.002, respectively).
Conclusion: This study evidences an association of CTLA-4  tagging polymorphisms and haplotypes with CRC risk. Additional well-designed studies with large sample sizes are required to confirm our findings.
Keywords: polymorphism, immune, CTLA-4 , tagging, colorectal cancer, susceptibility