The association between cytotoxic T lymphocyte-associated antigen-4 and cervical cancer

Abstract

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene polymorphisms have been associated with many autoimmune diseases and malignancy susceptibility, but the relationship between CTLA-4 and cervical cancer is still controversial. Hence, a meta-analysis of the published studies for the CTLA-4 gene polymorphisms and the risk of cervical cancer was performed to evaluate the association between them. Odds ratios (ORs) and 95% confidence intervals (CIs) for the codominant, dominant, and recessive genetic models were assessed. The fixed or random effect pooled measure was selected on the basis of the heterogeneity test among studies. The heterogeneity among studies was evaluated using the I (2). Eight studies with 2,835 cases and 2,560 controls were included. In seven studies for the CTLA-4 +49A/G polymorphism, a significant association was showed between the A allele and the increased risk of cervical cancer in the codominant (OR 1.16, 95% CI 1.05-1.29), dominant (OR 1.18, 95% CI 1.03-1.36), and recessive (OR 1.24, 95% CI 1.05-1.56) models. In five studies for the CTLA-4 -318C/T polymorphism, the meta-analysis showed a significant association of the C allele with the reduced risk of cervical cancer in the codominant (OR 0.79, 95% CI 0.66-0.94) and recessive (OR 0.76, 95% CI 0.63-0.93) models. This meta-analysis suggested that +49A/G and -318C/T polymorphisms of the CTLA-4 gene were significantly associated with the risk of cervical cancer. However, further studies are required to draw a solid conclusion on the relation between the CTLA-4 polymorphism and the risk of cervical cancer.

Immune Checkpoint Molecules—Inherited Variations as Markers for Cancer Risk

“…In a stratified analysis by ethnicity, a significant association was observed for CTLA-4c.-319*T allele in Asian, but not in Caucasian women. This meta-analysis confirmed the results of the previous studies ( 79 , 80 ). Of note, in study by Pawlak et al ( 73 ) the significant association between CTLA-4c.-319*T allele and G1 grade of tumor was found.…”

Association of CTLA‐4, TNF alpha and IL 10 polymorphisms with susceptibility to hepatocellular carcinoma

“…A large number of genetic association studies suggest that CTLA‐4 is an important susceptibility locus for autoimmune diseases and certain types of cancer; however, the mechanism by which polymorphism of CTLA‐4 acts to inhibit cancer remains unclear. Recently, several studies focused on the association of CTLA‐4 single nucleotide polymorphisms (SNPs) with susceptibility to various types of cancer, such as gastric cancer, cervical cancer, colorectal cancer and lung cancer . Also, a few case‐control studies focused on the association of CTLA‐4 SNPs with susceptibility to HCC .…”

“…Recently, several studies focused on the association of CTLA-4 single nucleotide polymorphisms (SNPs) with susceptibility to various types of cancer, such as gastric cancer, cervical cancer, colorectal cancer and lung cancer. [7][8][9][10] Also, a few case-control studies focused on the association of CTLA-4 SNPs with susceptibility to HCC. 11,12 However, due to the small sample size and the limited amount of data, the relationship between CTLA-4 SNPs and risk of HCC was not fully understood.…”

Genetic susceptibility to cervical cancer: role of common polymorphisms in apoptosis-related genes

“…The search for high penetrance genetic mutations associated with cervical cancer has proven difficult and has been unsuccessful. Given the fact that single nucleotide polymorphisms (SNPs) represent the most common form of genetic variation, many researchers have shifted their attention to investigate the presence of an association between SNPs in numerous carcinogenic/anti-carcinogenic pathways and susceptibility to cervical cancer in the past decades [9][10][11][12][13]. It has been thought that such low penetrance genetic polymorphisms could confer only modest risk for, or have only moderate protective effect against, cervical cancer if acting individually [52].…”

“…In the past decade, it has become more and more evident that host genetic factors and their corresponding protein products could play an equally important role in cervical carcinogenesis by interacting synergistically with HPV oncoproteins [7,8]. In addition, a large number of studies have demonstrated that polymorphic variations within host genetic factors could potentially contribute to the interindividual differences in susceptibility to cervical cancer [9][10][11][12][13]. This observation is particularly true for polymorphisms of host genes involved in the complex carcinogenic and/or anti-carcinogenic pathways.…”