Current Evidence on the Association between Cytotoxic T-Lymphocyte Antigen 4 +49G > A Polymorphism and Digestive System Cancer Risks: a Meta-analysis Involving 11,923 Subjects

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) plays an important role in downregulating T cell activation and proliferation. The CTLA-4 +49G > A polymorphism is one of the most commonly studied polymorphisms in this gene due to its association with many cancer types, but the association between CTLA-4 +49G > A polymorphism and digestive system cancer risks remain inconclusive. An updated meta-analysis based on 17 independent case-control studies consisting of 5,176 cancer patients and 6,747 controls was performed to address this association. Overall, there was no statistically increased risk of digestive system cancers in every genetic comparison.In subgroup analysis, this polymorphism was significantly linked to higherrisks for pancreatic cancer (GG vs. AA, OR=1.976, 95% CI = 1.496-2.611; GA vs. AA, OR=1.433, 95% CI = 1.093-1.879; GG/GA vs. AA, OR=1.668, 95% CI = 1.286-2.164; GG vs. GA/AA, OR = 1.502, 95% CI = 1.098-2.054; G vs. A, OR=1.394, 95%CI = 1.098-1.770). We also observed increased susceptibility of hepatocellular cell carcinoma in homozygote comparison (OR=1.433, 95% CI = 1.100-1.866) and dominant model (OR=1.360, 95% CI = 1.059-1.746). According to the source of controls, significant effects were only observed in hospital-based studies (GA/AA vs. GG, OR=1.257, 95% CI = 1.129-1.399). In the stratified analysis by ethnicity, No significantly increased risks were found in either Asian or Caucasian. Our findings suggest that the CTLA-4 +49G > A polymorphism may be not associated with an elevated digestive system cancer risks.